Reported Symptoms in Prodromal and Early Motor Parkinson's Disease: A Scoping Review on the Patient Perspective

Joseph Saade; Alice van Wyk; Glenn T Stebbins; Tiago A Mestre

doi:10.1002/mdc3.70007

. 2025 Mar 3;12(6):721–733. doi: 10.1002/mdc3.70007

Reported Symptoms in Prodromal and Early Motor Parkinson's Disease: A Scoping Review on the Patient Perspective

Joseph Saade ^1,^2,^✉, Alice van Wyk ³, Glenn T Stebbins ⁴, Tiago A Mestre ^1,⁵

PMCID: PMC12187961 PMID: 40029012

Abstract

Background

The lived experience of Parkinson's disease (PD) includes motor and non‐motor symptoms. There is a need to capture the earliest patient experiences in a sensitive and reliable manner for the successful development of interventions that may delay clinical progression in PD.

Objective

Our aim was to synthesize published literature about patient‐reported symptoms in prodromal and early motor stages of PD and develop a conceptual framework of the earliest lived experiences in PD.

Methods

We conducted a scoping review of the published literature in MEDLINE, EMBASE, SCOPUS, and CINAHL databases and abstracted patient‐reported symptoms from included studies reporting on prodromal or early motor stages of PD populations.

Results

We included 59 articles with data from 64 cohorts (prodromal PD: n = 20/64; 31%, early motor PD: n = 44/64, 69%). Overall, the 10 most frequent symptoms (of 85 standardized reported symptoms [SRSs]) were non‐motor. SRSs were grouped into symptom domains (behavioral, cognition, dysautonomia, motor, sensory, sleep, and others) and functional domains (activities of daily living, communication, sexual, and social impairment). The Movement Disorder Society sponsored revision of the Unified Parkinson's Disease Rating Scale parts Ib and II (n = 13/64, 20%) and ad hoc questionnaires (n = 12/64, 19%) were the most frequently used measurement tools.

Conclusion

At prodromal and early motor stages of PD, individuals report symptoms of a diverse range of motor and non‐motor domains and higher‐level functional domains. There is a need to capture the full spectrum of this lived experience in a new patient‐reported clinical outcome measure for clinical trials in the earliest clinical stages of PD.

Keywords: diagnosis, early stage, Parkinson's disease, patient reported outcome, prodromal, symptoms

The clinical diagnosis of Parkinson's disease (PD) is based on the presence of bradykinesia combined with either rigidity or resting tremor. ¹ However, non‐motor symptoms (NMS) are recognized as an integral part of the clinical presentation of PD and can precede the onset of motor symptoms (MS) by years or even decades. ² , ³ To identify individuals at risk of PD, the International Parkinson and Movement Disorder Society (MDS) has developed research criteria encompassing NMS such as rapid eye movement (REM) sleep behavior disorder (RBD), hyposmia, constipation, urinary and/or erectile dysfunction, fatigue, daytime somnolence and depression, and in addition to subtle non‐diagnostic motor features (bradykinesia, rigidity, gait impairment etc.) and neuroimaging of abnormal presynaptic dopaminergic function. ⁴

Individuals in the prodromal and early motor stages of PD experience a wide variety of symptoms, ⁵ which can be vague or atypical and challenge an initial diagnosis. ⁶ Nevertheless, several studies have established that the patients' perception of MS and NMS is associated with an increased risk for a clinical PD diagnosis. ⁷ , ⁸ Recognizing their relevance, patient‐reported symptoms of PD have been incorporated in the 2019 update version of the MDS‐supported diagnostic criteria of prodromal PD. ⁹ However, the literature lacks a comprehensive synthesis of these patient‐reported experiences across motor, non‐motor, and functional domains.

The growing interest in developing disease‐modifying therapies at the earliest stages of PD, namely the pre‐motor stage, ¹⁰ underscores the need for patient‐reported outcomes (PROs) that are valid, reliable, and sensitive at these stages of PD. In addition, regulatory bodies such as the United States (US) Food Drug Administration (FDA) recognize the importance of the patient voice in the development of outcomes measures, and require high‐quality patient centered data to support drug labeling claims. ¹¹ Currently, there is no PRO that comprehensively addresses the multidimensional and evolving nature of symptoms in the prodromal and early motor stages of PD.

In this context, we conducted a scoping review to synthesize the existing literature for patient‐reported symptoms at prodromal and early motor PD stages, providing a structured and comprehensive overview of patient‐reported symptoms across different domains and corresponding measurement tools to document them. It is our ultimate aim to develop a conceptual framework that informs the design of a novel PRO measure tailored to a peri‐diagnostic period in PD natural history, that effectively captures the earliest clinical changes in PD before clinical diagnosis (prodromal PD) and the patient experience at the time of a clinical diagnosis of PD (early motor PD).

Methods

A preliminary search of PROSPERO, MEDLINE, and the Cochrane Database of Systematic Reviews was conducted before initiating this review. No published or in‐progress scoping reviews on this topic were identified. We conducted this scoping review in accordance with the Joanna Briggs Institute methodology ¹² and followed the Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) framework. ¹³

The primary research question was: what are the symptoms reported by individuals at a prodromal or early motor PD stage? The secondary research questions were: (1) what are the different domains of functioning that are impacted at these two stages of PD? and (2) what are the measurement tools used to capture these changes?

Inclusion/Exclusion Criteria

The population consisted of adults diagnosed with prodromal or early motor PD. Prodromal PD was defined as retrospective assessments of pre‐motor experiences for patients with clinical PD, development of a PD diagnosis in a prospective follow‐up studies in the general population, or meeting the MDS research criteria for prodromal PD risk. ⁹ Early motor PD was defined as a diagnosis of clinical PD within 2 years of study participation. A dopaminergic deficit documented by neuroimaging was not required.

The concept included PROs or qualitative methods that collect information on motor and NMS as reported by the subject.

The context included published literature in English or French of any qualitative and quantitative studies, regardless of the geographic location. We only included peer‐reviewed full‐text publication and excluded conference abstracts, gray literature or publications in other languages.

Search Strategy

We systematically searched four electronic databases—MEDLINE, EMBASE, SCOPUS, and CINAHL—from inception to May 15, 2022, the date of the most recent search. The search strategy included a combination of keywords and MeSH terms: Parkinson, prodromal, stage, presentation, onset, earliest, early, de novo, drug‐naïve, symptom, change, present, manifest, appear, start, emerge, occur, surface, perceive, percept, notice, see, observe, discern, detect. Keywords were grouped into different clusters using ‘OR’ and combined across clusters using ‘AND’. A detailed research strategy is in Appendix S1 in the Supporting information.

Screening Process

Three authors (A.v.W., J.S., and T.A.M.) independently screened all the abstracts and full texts in a two‐stage approach using the Covidence platform (covidence.org). Conflicts were resolved through consensus discussions among the reviewers. Reasons for exclusions at each stage were documented in the PRISMA‐ScR flow diagram (Fig. 1).

FIG. 1 — Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) flowchart.

Data Extraction

We extracted the following data from each study.

(1) Study characteristics including: title, authors, year and country of publication, study design, sample size, and aims.

(2) Population characteristics including: age, gender, and disease stage (prodromal or early motor), genetic information, dopaminergic treatment status (treatment‐naive vs. treated).

(3) Reported outcomes including: patient‐reported symptoms or changes from normal, the clinical measures used for each symptom and the frequency of the symptom or the score of the scale used, when applicable. We considered gender‐based stratification of results when available.

Data extraction was performed by one author (A.v.W.) and independently reviewed by a second author (J.S.) Any discrepancies were discussed with T.A.M. For scales that include both clinician‐rated and patient‐reported components, only the PROs component was extracted. For example, in the International Parkinson and Movement Disorder Society sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), ¹⁴ we considered parts Ib and II.

Data Analyses

We analyzed data for the whole PD population at a prodromal or early motor PD stages. Symptoms reported repeatedly in prospective studies were included only once, at the time of PD diagnosis. We reviewed reported symptoms and those with a frequency of zero or a null score (denoting absence) were excluded. The remainder was grouped as standardized reported symptoms (SRSs) into seven symptom domains: dysautonomia, motor, sensory, behavioral, cognition, sleep and miscellaneous. Additionally, SRSs that reflected changes in patient functioning or quality of life or involved various domains were considered for functional domains (activities of daily living [ADL], communication, social and sexual impairment) to avoid subjective interpretation of data and assumption bias. We calculated the frequency of reporting of each SRS and metric. Because of significant heterogeneity in reporting metrics across studies, a pooled frequency of SRSs could not be estimated.

Results

The initial literature search yielded a total of 2687 references, of which 59 studies were included (Fig. 1).

Description of Included Studies

Among the included studies, 27% (16/59) evaluated individuals at a prodromal PD stage and 66% (39/59) included early motor PD patients. Four studies (7%) included participants in both disease stages, and conducted comparative analyses of symptoms' distribution. ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ Four prodromal PD studies aimed to investigate the individual self‐perception of symptoms and compare it to a physician‐rated clinical assessment. ³ , ¹⁹ , ²⁰ , ²¹ Five studies evaluated the association of reported symptoms and the time of a clinical PD diagnosis. ⁸ , ²² , ²³ , ²⁴ , ²⁵ Common aims across the early motor PD cohort studies included investigating the presence, severity, or frequency of a specific symptom (e.g., orthostatic hypotension, RDB, fatigue) ²⁶ , ²⁷ , ²⁸ or a group of symptoms (e.g., gastrointestinal or urogenital symptoms, cognitive impairment), ²⁹ , ³⁰ , ³¹ or to develop and validate a specific measurement tool such as the MDS‐UPDRS, Apathy Evaluation Scale‐Self Report (AES‐S) ³² or Parkinson's Disease Sleep Scale. ³³ , ³⁴ , ³⁵ , ³⁶

We identified 64 independent cohorts of which 31% (n = 20) included prodromal PD subjects and 69% (n = 44) included early motor PD patients. In some prodromal PD cohorts, participants shared a common characteristic, for example, RBD as an inclusion criterion ¹⁶ or stratification based on GBA1 and LRRK2 genetic status. ¹⁷ , ³⁷ , ³⁸ No other known risk factors for clinical PD were considered in the remaining prodromal cohorts.

Overall, the included studies reported on a total of 24,473 subjects. The study‐level mean age of study participants varied from 49.1 to 78.8 years. In terms of study design, 47% (n = 28) of studies were cross‐sectional, 27% (n = 16) were cohort studies, 18% (n = 11) were case–control studies. There were three RCTs, a case report study, and a case series report. The list of included studies, with study design, study aim, and population characteristics, including PD population size, median age, and frequency of female participants are available in Table S1.

Individual Experiences at Prodromal and Early Motor Stages of PD

We identified a total of 461 individually reported symptoms, corresponding to 85 SRSs. For example, “malfunctioning of a self‐winding wristwatch,” “reduced arm movement,” “bradykinesia,” and “slow movement” were clustered into bradykinesia. The complete list of reported symptoms and corresponding SRSs is available in Table S2.

The 10 most reported SRSs in prodromal PD were constipation (65%), depression (55%), tremor (50%), bradykinesia, hyposmia (45% each), pain, RBD (40% each), anxiety, apathy, and hyperhidrosis (35% each). The 10 most SRSs reported in early motor PD were depression (55%), apathy (50%), anxiety, constipation, daytime sleepiness, sleep difficulties not otherwise specified (NOS) (45% each), urinary symptoms NOS (41%), sexual dysfunction (39%), fatigue, and pain (36% each).

Olfactory symptoms NOS (15%), bowel incontinence, bradyphrenia, dysarthria, hypophonia (each 10% each), and dysphoria (5%) were exclusively reported in prodromal PD populations. The SRSs solely reported in the early motor PD cohorts were divided into three groups based on the number of studies that reported them: (1) impulse control behaviors, urinary frequency, and difficulty with ADLs NOS were reported in more than 10% of the cohorts; (2) anismus/tenesmus, communication, difficulty with inter‐personal relations, fecal incontinence, incomplete voiding, appetite changes, syncope, and urinary hesitancy were reported in 5 to 10% of cohorts; and (3) aggressivity, irritability, diarrhea, disorganization, executive dysfunction, numbness, odynophagia, perseveration, poor judgment, restlessness, and rhinorrhea were reported in less than 5% of cohorts (see Fig. 2 for a complete report and distribution of SRSs in prodromal and early motor PD populations).

FIG. 2 — Frequency of standardized reported symptoms (SRSs) in prodromal and early motor Parkinson's disease (PD) cohorts. Symptoms are ranked in descending order based on their overall frequency across both disease stages.

Patient‐Reported Measures

A total of 44 measurement tools were identified in the included studies. They comprised questionnaires, rating scales, and qualitative methodologies. Questionnaires included ad hoc questionnaires ³ , ¹⁵ , ¹⁷ , ²⁰ , ³⁹ , ⁴⁰ or questionnaires used in non‐PD conditions and adapted for the study purpose. ²⁰ , ⁴¹ , ⁴²

PROs used in both populations included, by order of frequency, the MDS‐UPDRS parts Ib+II (20%), ad hoc questionnaire (19%), interview (16%), Epworth sleepiness scale (ESS) ⁴³ (14%), REM sleep behavior disorder severity scale (RBDSQ) ⁴⁴ (13%), geriatric depression scale (GDS), ⁴⁵ scales for outcomes in PD‐autonomic dysfunction (SCOPA‐AUT) ⁴⁶ and University of Pennsylvania smell identification test (UPSIT) ⁴⁷ (11% each), Non‐Motor Symptoms Questionnaire (NMSQ) ⁴⁸ (8%), UPDRS and symptoms per verbatim (6%), Beck Depression Inventory (BDI) ⁴⁹ (5%), survey and Unified Multiple System Atrophy Rating Scale (UMSARS) ⁵⁰ (3% each). The UMSARS was used in one study ¹⁶ to rate three dysautonomic symptoms: constipation, urinary dysfunction, and erectile dysfunction.

In prodromal PD populations, the five most frequently used measurement tools were: ad hoc questionnaires and interview (30% each), medical records review (15%), UPSIT, NMSQ, symptoms per verbatim, and Brief Smell Identification Test (B‐SIT) ⁵¹ (10% each). In the early motor PD group, the five most frequently used measurement tools were the MDS‐UPDRS parts Ib+II (27%), ESS (18%), RBDSQ (16%), GDS, Non‐Motor Symptoms Scale for Parkinson's Disease (NMSS), ⁵² ad hoc questionnaire, and SCOPA‐AUT (14% each) (Fig. 3). Four studies, ⁶ , ²⁵ , ⁵³ , ⁵⁴ two in each disease stage, provided a verbatim report of symptoms expressed by study participants.

FIG. 3 — Measurement tools used in prodromal and early motor Parkinson's disease (PD) cohorts. ADQ, Anticholinergic Drug Scale; AES‐S, Apathy Evaluation Scale‐self report; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; B‐SIT, Brief Smell Identification test; CES‐D‐10, Center for Epidemiologic Studies Depression Scale‐10 item; ESS, Epworth Sleepiness Scale; FBI, Freezing Of Gait Questionnaire; FSS, Fatigue Severity Scale; GDS, Geriatric Depression Scale; HADS, Hospital Anxiety And Depression Scale; HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; KVSS, Kuppuswamy's Socio‐Economic Status Scale; LADS, Lille Apathy Rating Scale; MADRS, Montgomery‐Asberg Depression Rating Scale; MDS‐UPDRS, Movement Disorder Society Unified Parkinson's Disease Rating Scale; NMSQ, Non‐Motor Symptoms Questionnaire; NMSS, Non‐Motor Symptoms Scale; NPI‐Q, Neuropsychiatric Inventory Questionnaire; PDQ‐39, Parkinson's Disease Questionnaire‐39; PDSS, Parkinson's Disease Sleep Scale; PDSS‐2, Parkinson's Disease Sleep Scale‐2; PFS, Parkinson's Fatigue Scale; PSQI, Pittsburgh Sleep Quality Index; QUIP, Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's Disease; QUIP‐RS, Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's Disease‐rating scale; RBDSQ, REM Sleep Behavior Disorder Screening Questionnaire; SAS, Zung Self‐Rating Anxiety Scale; SCOPA‐AUT, Scales for Outcomes in Parkinson's Disease‐Autonomic; SCS‐PD, scales for outcomes in Parkinson's disease‐psychosocial; SS/SS‐12, Sniffin' sticks test; STAI, State–Trait Anxiety Inventory; UMSARS, Unified Multiple System Atrophy Rating Scale; UPDRS, Unified Parkinson's Disease Rating Scale; UPSIT, University of Pennsylvania Smell Identification Test; U‐UDI, Urogenital Distress Inventor.

Population‐Specific Characteristics

Only two early motor PD studies reported results stratified by participants' gender. ⁵⁵ , ⁵⁶

Cognitive, behavioral, sleep, and dysautonomia domains were studied in both studies, although only three individual SRSs were studied in both: sexual dysfunction, insomnia, and daytime sleepiness. One study relied exclusively on the NMSQ to report symptoms across various domains, whereas the other study used three different measurement tools: Pittsburgh Sleep Quality Index for reporting three sleep‐related symptoms, the BDI for assessing depression, and the NMSS for capturing the remaining SRSs. In these studies, MS were reported using clinician‐rated scales (MDS‐UPDRS part III) and, therefore, were not considered for the purpose of this review. In one paper, NMS were present in both genders, however, men experienced more sexual dysfunction symptoms, and women displayed more behavioral symptoms like depression. ⁵⁵ While in the other study, men were more prone to developing drooling and nocturia, regardless of having started or not dopaminergic therapy. ⁵⁶

Two studies stratified participants based on their genetic status related to PD. The first study divided participants into three groups: idiopathic PD patients, GBA1 mutation carriers, and LRRK2 mutation carriers. ¹⁷ Patient‐reported symptoms were collected across both prodromal and early motor PD stages. The second study focused exclusively on asymptomatic LRRK2 mutation. ³⁸ Across both studies, several overlapping SRSs were identified, including cognitive impairment (NOS), sexual dysfunction, hyposmia, constipation, and depression. Measurement tools varied between the two, the first study used only questionnaires to assess symptom presence, whereas the second study used six different instruments: ESS, GDS, MDS‐UPDRS, RBDSQ, SCOPA‐AUT, and UPSIT. MS were extracted from the first study only that used patient‐reported tool. These findings highlight differences in methodology that may limit a comparative analysis of reported symptoms.

Toward a Conceptual Framework for the Earliest Lived Experiences in PD

In this section, we present the main findings by symptom and functional domains, organized in a descending order, from the one with the most SRSs to the one with the fewest. For each domain, we highlighted the top five most frequently reported SRSs and the three most commonly used measurement tools.

Symptom Domains

Dysautonomia

This domain incorporates a wide range of symptoms from different body systems (gastrointestinal, genitourinary, and cardiovascular) in a total 28 SRSs (Table 1). Dysautonomia was studied in 75% of the prodromal PD cohorts (n = 15) and 73% of early motor PD cohorts (n = 32). The five most frequently reported dysautonomic SRSs in prodromal PD cohorts were constipation (n = 13), hyperhidrosis (n = 7), sexual dysfunction (n = 6), orthostatic symptoms (n = 5), and urinary symptoms NOS, sialorrhea, and dysphagia (n = 4 each). In early motor PD cohorts, the five most frequently reported SRSs included constipation (n = 20), urinary symptoms NOS (n = 18), sexual dysfunction (n = 17), dysphagia, and sialorrhea (n = 15 each). Fifteen different measures were used to evaluate this domain. The three most used measurement tools were interviews (n = 4), questionnaires, and medical records review (n = 3 each) in prodromal PD cohorts, and the MDS‐UPDRS parts Ib+II (n = 9), NMSS, and SCOPA‐AUT (n = 6 each) in early motor PD cohorts.

TABLE 1.

Results

	A. Domain			B. SRS per domain			C. Measurement tools
	Prodromal PD (N = 20), n (%)	Early motor PD (N = 44), n (%)	Total (N = 64) n (%)	Prodromal PD, n (%)	Early motor PD, n (%)	Total per domain, n (%)	Prodromal PD (n)	Early motor PD (n)	Total (n)
Symptom domains				63 (100)	76 (100)	82 (100)
Dysautonomia	15 (75)	32 (73)	47 (73)	20 (32)	27 (36)	28 (34)	9	24	27
Motor	14 (70)	21 (48)	35 (55)	15 (24)	13 (17)	15 (18)	10	16	19
Sensory	18 (90)	30 (68)	48 (75)	9 (14)	11 (14)	12 (15)	9	12	15
Behavioral	14 (70)	31 (70)	45 (70)	8 (13)	10 (13)	11 (13)	7	12	12
Cognition	12 (60)	20 (45)	32 (50)	6 (10)	9 (12)	10 (12)	7	12	12
Sleep	13 (65)	28 (64)	41 (64)	4 (6)	4 (5)	4 (5)	7	8	10
Miscellaneous	1 (5)	8 (18)	9 (14)	1 (2)	2 (3)	2 (2)	1	5	5
Function domains				8 (100)	21 (100)	23 (100)
ADL	6 (30)	20 (45)	26 (41)	4 (50)	12 (57)	13 (5)	4	12	12
Communication	5 (25)	13 (30)	18 (28)	3 (44)	4 (19)	5 (22)	5	8	9
Social impairment	0 (0)	6 (14)	6 (9)	0 (0)	3 (14)	3 (13)	4	7	6
Sexual impairment	6 (30)	19 (43)	25 (39)	1 (11)	2 (10)	2 (9)	0	4	4

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Notes: A. Reporting of symptom and functional domains in prodromal and early motor PD cohorts (counts and frequency are presented). B. Number and frequency of SRSs for each domain, per disease stage. C. Number of measurement tools used in each domain, per disease stage. Bold values highlight that the data is the total for each domain.

Abbreviations: SRSs, standardized reported symptom; PD, Parkinson's disease; ADL, activities of daily living.

Motor

This domain includes a total of 15 motor SRSs and was evaluated in 70% prodromal PD cohorts (n = 14) and in 48% early motor PD cohorts (n = 21) (Table 1). The five most frequently reported SRSs in prodromal PD cohorts were tremor (n = 10), bradykinesia (n = 9), and rigidity/hand dexterity/balance impairment NOS (n = 6 each). Tremor, MS NOS (n = 10), and hand dexterity, reduced mobility, and speech changes (n = 9 each) were the five most frequently reported symptoms in early motor PD cohorts. A total of 15 different measurement tools were used. Interviews (n = 4), questionnaires (n = 3), NMSQ, symptoms per verbatim, and medical records review (n = 2 each) were more commonly used in prodromal PD cohorts, and the MDS‐UPDRS parts Ib+II (n = 4), Parkinson's Disease Questionnaire (PDQ‐39), ⁵⁷ and ad hoc questionnaires (n = 3) were more commonly used in early motor PD cohorts.

Sensory

This domain included a total of 12 SRSs, reported in 90% of prodromal PD cohorts, (n = 18) and 68% of early motor PD cohorts (n = 30) (Table 1). Hyposmia (n = 9), pain (n = 8), visual symptoms NOS (n = 5), fatigue (n = 4), and olfactory symptoms NOS (n = 3) were the five most frequently reported sensory SRSs in prodromal PD cohorts. Pain and fatigue (n = 16 each), hyposmia (n = 13), and visual symptoms NOS/sensory symptoms NOS (n = 7 each) were the five most frequently reported sensory SRSs in the early motor PD cohorts. A total of 19 measurement tools were used to assess a sensory domain including ad hoc questionnaires, interview, and medical records review (n = 3 each) in prodromal PD cohorts, and MDS‐UPDRS/UPSIT (n = 5 each) followed by questionnaire/Fatigue Severity Scale (FSS) ⁵⁸ (n = 4 each) in the early motor PD cohorts.

Behavioral

This domain included a total of 11 SRSs and was studied in 70% of both prodromal (n = 14) and early motor PD (n = 31) cohorts (Table 1). The five most frequently reported SRS were depression (n = 11), apathy/anxiety (n = 7 each), behavioral symptoms NOS (n = 5), and psychosis (n = 2) in prodromal PD cohorts. Depression (n = 24), apathy (n = 22), anxiety (n = 20), psychosis (n = 15), and behavioral symptoms NOS/impulse control behavior (n = 8 each) were the five most frequently reported SRSs in early motor PD cohorts. The behavioral domain was assessed using 27 measurement tools (Table 1C). The top three used measurement tools in prodromal PD cohorts included interviews, review of medical charts (n = 3 each), questionnaire, and NMSQ (n = 2 each) and included the GDS, MDS‐UPDRS parts Ib+II, and NMSS (n = 6) in early motor PD cohorts.

Cognitive

The cognitive domain included 10 SRSs related to memory, attention, and executive abilities. It was studied in 60% of prodromal PD (n = 12) and 45% of early motor PD (n = 20) cohorts (Table 1A).

The five most frequently reported SRSs in prodromal PD cohorts included cognitive impairment or memory symptoms NOS (n = 6 each), followed by bradyphrenia/language difficulties (n = 2 each) and last attention/memory symptoms NOS and concentrating difficulties (n = 1 each). Disorganization, executive dysfunction, perseveration, and poor judgment were not reported in the prodromal PD cohorts. Cognitive impairment NOS (n = 9), memory symptoms NOS (n = 8), attention/memory symptoms NOS (n = 7), concentrating difficulties (n = 5), and language difficulties (n = 2) were the five most frequently reported SRSs in the early motor PD cohorts (Fig. 4), and bradyphrenia was not reported. Ten measurement tools were used to measure the cognitive domain, and questionnaires/interview (n = 3) and medical records review (n = 2) were more frequently used in prodromal PD cohorts. The NMSS (n = 6), MDS‐UPDRS (n = 4), questionnaires/NMSQ/PDQ‐39 (n = 3) were the top three measurement tools used in early motor PD cohorts.

FIG. 4 — Conceptual model of reported experiences classified across symptom and function domains in prodromal and early motor stages of Parkinson's disease (PD).

Sleep

A total of four SRSs were included in this domain reported in 65% of prodromal PD (n = 13) and 64% of early PD cohorts (n = 28, Table 1). RBD was the most studied symptom in prodromal PD cohorts (n = 8), followed by sleep difficulties NOS, insomnia (n = 6 each), and daytime sleepiness (n = 5). In early motor PD cohorts, sleep difficulties NOS and daytime sleepiness were the most commonly studied SRSs (n = 20 each), second was RBS (n = 14) and insomnia was third (n = 10). Thirteen measurement tools were used: interviews and questionnaires (n = 4 each), NMSQ, and medical records review (n = 2 each) were the most used in prodromal PD cohorts, and the ESS (n = 8), RBDSQ, and MDS‐UPDRS (n = 3 each) were more commonly used in early motor PD cohorts.

Miscellaneous

We included weight and appetite changes in this domain that were studied in 5% (n = 1) of prodromal PD cohorts, and 18% (n = 8) of early PD cohorts (Table 1). Prodromal PD cohorts assessed only weight changes, whereas early motor PD cohorts assessed both SRSs (Fig. 4).

Overall, five measurement tools were used in this domain. Only the NMSQ was used in a single prodromal PD cohort. The NMSQ (n = 4), NMSS (n = 2) Neuropsychiatric Inventory–Questionnaire ⁵⁹ /questionnaire/SCOPA‐AUT (n = 1 each) were used in early PD cohorts.

Function Domains

ADL

The ADL domain includes a total of 13 SRSs reported in 30% of prodromal PD (n = 6) and 45% (n = 20) of early motor PD cohorts (Table 1). Four SRSs were studied in prodromal PD cohorts: hand dexterity (n = 6) and dressing difficulties/hygiene/rigidity (n = 1). The five most studied SRSs in early motor PD cohorts included hand dexterity (n = 9), dressing difficulties, hygiene, difficulty with ADLs NOS (n = 5), and MS NOS (n = 4). Rigidity/stiffness was not studied in prodromal PD cohorts. A total of 12 different measurement tools were used for this domain. Interviews and verbatim report of symptoms (n = 2 each) in addition to the UPDRS and questionnaire (n = 1) were more commonly used in prodromal PD cohorts, whereas the three most used tools in early motor PD cohorts included the UPDRS, MDS‐UPDRS parts Ib+II, and PDQ‐39 (n = 3 each).

Communication

Five SRSs were assigned to this domain reported in 25% of prodromal PD (n = 5) and 30% of early motor PD cohorts (n = 13, Table 1). Speech changes (n = 2), language difficulties (n = 2), and MS NOS (n = 1) were the three SRS studied in prodromal PD cohorts. In early motor PD cohorts, reported SRSs included speech changes (n = 9), communication (n = 4), language difficulties (n = 2), and perseveration (n = 1). Seven tools were used to assess SRS in the communication domain. In prodromal PD cohorts, NMSQ (n = 2), followed by questionnaire, survey, and UPDRS (n = 1 each) were used. In the early motor PD cohorts, the three most used tools included the MDS‐UPDRS part Ib+II (n = 4), followed by PDQ‐39 (n = 3), and an ad hoc questionnaire (n = 2).

Social Impairment

Three SRSs were included in this domain that included difficulty with inter‐personal relations (n = 4), behavioral symptoms NOS (n = 2), and apathy (n = 1). These SRSs were reported in early PD cohorts exclusively (14%, n = 6) (Table 1). The following four scales were used: PDQ‐39 (n = 3), AES, Freezing of Gait Questionnaire, and interview (n = 1 each).

Sexual Impairment

The sexual impairment domain was created to accommodate SRSs of sexual dysfunction and sex‐related impulse control behavior. It was studied in 30% (n = 6) of prodromal PD and 45% (n = 20) of early motor PD cohorts. Sexual dysfunction was reported exclusively in six prodromal PD cohorts. In early motor PD cohorts, sexual dysfunction was reported in 16 cohorts, and sex‐related impulse control behavior was reported in two cohorts. In prodromal PD cohorts, NMSQ was used more commonly (n = 2) followed by questionnaire, SCOPA‐AUT, UMSARS, and medical records review (n = 1). In early motor PD cohorts, NMSS was the most used tool (n = 6) followed by NMSQ, questionnaire, and SCOPA‐AUT (n = 3 each).

In this scoping review, we provide a comprehensive overview of the available information on the earliest lived experiences of individuals during prodromal and early motor stages of PD, which entails a myriad of isolated symptoms and meaningful changes in functioning with impacts in ADL and social interaction. The inclusion of both qualitative and quantitative studies across diverse populations strengthens the comprehensiveness of this review. Additionally, the focus on patient‐reported symptoms provides a unique perspective, aligning with the increasing recognition of the patient voice when measuring clinically meaningful changes in PD. Our findings are consistent with published literature identifying the importance of NMS (Fig. 2) in both prodromal and early motor PD stages. ² , ⁶⁰ Interestingly, tremor, a cardinal motor feature for a PD diagnosis ranked only 13th and other key MS (impaired hand dexterity and bradykinesia) ranked lower (20th and 22nd, respectively). This distribution underscores the critical need for PRO measures that include both NMS and MS to comprehensively evaluate the earliest clinical changes in PD.

Domain‐Specific Patient‐Reported Changes

Dysautonomia emerged as the symptom domain with the most SRSs reported overall, namely constipation and urinary symptoms. These findings are consistent with prior studies highlighting the relevance of autonomic changes as early indicators of PD. ²⁹ , ⁶¹

Depression was the most frequently reported SRS followed close by two other behavioral symptoms, apathy and anxiety. Of note, in the behavioral domain, psychosis emerged as one of the top five symptoms, predominantly in early motor PD cohorts. This aligns with evidence that minor hallucinations in early PD, even in patients naïve to dopaminergic therapy. ³¹ These four neuropsychiatric symptoms when present in peri‐diagnostic stages are associated with greater disease burden and disability, which negatively impact patients’ life. ⁶² Therefore, early detection and timely treatment of these symptoms are crucial for improving patient outcomes.

The motor domain was frequently ranked in prodromal PD cohorts with frequent reporting of core PD motor features ¹ such as tremor, bradykinesia, hand dexterity issues, and balance impairment. This finding supports the need to capture the experience of mild motor features before the emergence of definite parkinsonism consistent with prior findings that subjective changes in physical activity and motor function are strongly associated with a future clinical diagnosis of PD. ³⁹ In contrast, rigidity was less frequently reported, which suggests a lesser importance when capturing the patient lived experience.

Changes in hand dexterity were reported in 23% (n = 15) of cohorts and were included in both motor and ADLs domains. The hand dexterity item is a good example on how a symptom can be valued on itself and by its functional impact in early clinical PD, ⁶³ and highlights the need to consider functional domains to characterize the earliest lived experience in PD. This observation is consistent with recent data suggesting that onset of functional decline up to 3 years before a formal PD diagnosis, reflecting the early emergence of mild parkinsonian symptoms and non‐motor features. ⁶⁴

The sensory domain emerged as a the most frequently studied symptom domain across cohorts, particularly in prodromal PD. Hyposmia was a notably prominent sensory reported in half of the prodromal cohorts, consistent with its established role as an early biomarker of PD. ⁴ The high prevalence of hyposmia in early motor PD cohorts further underscores its persistence throughout disease progression. These findings reinforce current efforts to incorporate simplified smell tests into PD risk assessment scales to improve the detection of individuals at risk of developing PD. ⁶⁵ Pain emerges as a significant symptom in both PD stages. The prevalence of pain in these peri‐diagnostic stages suggests that it may be an intrinsic feature of PD pathophysiology rather than solely a consequence of MS. ⁶⁶ , ⁶⁷ This finding emphasizes the need to consider pain when evaluating the clinical disease at early PD stages or optimizing management.

A Conceptual Model of the Earliest Lived Experiences in PD

A key outcome of this review is the development of a conceptual model (Fig. 4) that organizes lived experiences into 11 domains of symptoms experiences and functional impacts, encompassing 40 distinct patient‐reported symptoms. The consideration of these domains ensures a holistic portrait of the lived experience of PD early in its clinical course and enhances the relevance and utility of future PROs in capturing meaningful outcomes for patients. We are confident that this conceptual model provides a comprehensive qualitative structured foundation for item generation and content validation of a PRO to be administered in the future to people living at a prodromal state of PD or with a recent clinical diagnosis of PD, namely, for prevention trials. ⁶⁸ , ⁶⁹

Measurement Tools for the Earliest Lived Experiences in PD

An important finding of our review was the observed heterogeneity of the measurement tools used to assess patient‐reported symptoms. Sixteen different instruments were used across studies, reflecting a lack of consensus on standardized assessment methods for this disease stage. The analysis showed a notable reliance on a mix of well‐established tools, such as MDS‐UPDRS, ESS, and RBDSQ, alongside ad hoc questionnaires and interview, to capture patient‐reported symptoms, which lack validation and specificity for the earliest stages of PD. The MDS‐UPDRS continues to be the gold standard measurement tool for PD. MDS‐UPDRS parts Ib and II were the most frequently used PROs in early motor PD cohorts (n = 12, 27%) and used in only one prodromal PD cohort (5%). The MDS‐UPDRS measures eight of the 11 studied domains, with the exception of weight and appetite changes, social, and sexual impairment. Part I of the MDS‐UPDRS may be considered as an initial screening tool for common neuropsychiatric symptoms in PD, particularly because it has been validated in this population, unlike other symptom‐specific tools. ⁷⁰ However, results from MDS‐UPDRS part II can be influenced by NMS and not necessarily evaluate pure motor function. ⁷¹ Furthermore, the MDS‐UPDRS is sub‐optimal at detecting subtle motor changes in early motor PD stage, which can be experienced by patients ⁷² and their impact on daily functioning. ⁷³ , ⁷⁴ NMSS and NMSQ scales, although initially designed for NMS assessment, captured symptoms across seven symptom domains and a sexual impairment domain, in addition to ADLs for NMSQ. The NMSS developed from NMSQ reflects the burden of NMS and impact on quality of life of patients. ⁷⁵ However, these scales were tested in PD patients across disease stages ⁵² and, to our knowledge, validity of these NMS scales in prodromal and early motor PD patients has not been completed.

The predominant use of ad hoc measurement tools in prodromal PD studies (30%) further highlights the existing gaps in assessing diverse and evolving symptoms at this stage. Ad hoc questionnaires and interviews were used broadly across domains covering a wide range of symptoms. However, the lack of standardization may limit their ability to capture the full spectrum of patient experiences and emphasizes the unmet need for a unified, sensitive, and disease‐stage‐specific PRO tool to comprehensively evaluate the peri‐diagnostic period of PD.

Limitations

In our review, we found that study reports lacked granularity that prevented a greater insight and confidence about identifying full spectrum of symptom. For example, sleeping difficulties NOS, the fifth most common SRSs, included symptoms like “sleep problems” and “sleep disturbances” that were rather generic and difficult to interpret even after reviewing the used assessment tool.

The observed heterogeneity in measurement tools precluded pooled analysis of specific symptoms across studies and a better determination of their relative weight in early lived experience. The available data also limited the relevant discussion centered on gender or genetic background. Clinical presentation and treatment response can differ between genders such as women tend to present with tremor, whereas men have more severe MS and a younger age of onset of parkinsonism. ⁷⁶ Similarly, patients with specific genetic mutations, such as those in GBA1 or LRRK2 genes, may exhibit distinct symptom profiles or disease trajectories. For instance, GBA1 mutation carriers had an earlier disease onset and more rapid progression of both MS and NMS, particularly for cognitive decline, ⁷⁷ whereas LRRK2 mutation carriers had a milder disease presentation. ⁷⁸

Furthermore, the exclusion of non‐English and non‐French studies may limit the generalizability of the findings, particularly, to non‐Western contexts. Gray literature or social media was not included in our search, which could have provided further insights on the earliest lived experiences in not captured in peer‐review literature. However, it would have been challenging to determine the certainty of their clinical diagnosis and identify disease stage on social media outlets and online forums. ⁷²

Conclusion

The current review summarizes the published literature for the lived experience of individuals deemed to be at prodromal or early motor stages of PD and informed the development of a conceptual framework foundational to the creation of a PRO sensitive to the multi‐domain symptom presentation in early PD, namely, as it relates to the generation of scale items and content validity. ⁶⁹

We believe the current review is timely, because there is an urgent need for a validated comprehensive PRO measure that can support clinical trial platforms such as the Pathway to Prevention Program ⁷⁹ or the Edmond J. Safra Accelerating Clinical Treatments for Parkinson's Disease ⁸⁰ in demonstrating a clinically meaningful effect of putative disease modifying therapies at the earliest stages of PD.

Author Role

(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

J.S.: 1C, 3A

A.V.W.: 1C

G.S.: 3B

T.M.: 1A, 3B

Disclosures

Ethical Compliance Statement: This study didn't require any approval from an institutional review board or ethics committee. It didn't involve any human or animal intervention. Informed patient consent was not necessary for this work. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: J. S. and A.v.W. have no funding to report. G.T.S. effort on this project was supported by The Michael J. Fox Foundation for Parkinson's Research. T.M. effort on this project was supported by The Michael J. Fox Foundation for Parkinson's Research.

Financial Disclosures for the Previous 12 Months: J.S. and A.v.W. have no additional disclosures to report. G.T.S. had compensations for consulting and being an Advisory Board member for the following organizations: Adamas Pharmaceuticals, CHDI Management, Cleveland Clinic Foundation, Contera Pharma, Huntington Study Group, Lilly USA, Neurocrine Biosciences, Pfizer, Vima Therapeutics, and WCG Clinical. G.T.S. received research grants from the following organizations: Critical Path Institute, Department of Defense, Dystonia Coalition, CHDI, International Parkinson and Movement Disorder Society, The Michael J. Fox Foundation for Parkinson's Research, Ottawa Hospital Research Institute, and University of California at San Diego. He also received compensations from the following organizations: Alzheimer's Association, Critical Path Institute, International Parkinson and Movement Disorder Society, and The Michael J. Fox Foundation for Parkinson's Research. T.A.M. had compensations for consulting and being an Advisory Board member for the following organizations: AbbVie, International Parkinson and Movement Disorder Society, AAN, AbbVie, CHDI Foundation/Management, Sunovion, Valeo Pharma, Roche, nQ Medical, and Medtronic. T.A.M. received research grants from the following organizations: EU Joint Program‐Neurodegenerative Disease Research, uOBMRI, Roche, Ontario Research Fund, CIHR, The Michael J. Fox Foundation, Parkinson Canada, PDF/PSG, LesLois Foundation, PSI Foundation, Parkinson Research Consortium and Brain Canada.

Supporting information

Appendix S1. Research strategy (MEDLINE).

Table S1. Included studies and population demographics.

Table S2. List of extracted reported symptoms for each standardized reported symptom (SRS) and tools used to measure the symptoms.

MDC3-12-721-s001.docx^{(74.1KB, docx)}

Acknowledgments

The authors have no acknowledgments to report.

Relevant disclosures and conflict of interest are listed at the end of this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

1. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease: MDS‐PD Clinical Diagnostic Criteria. Mov Disord 2015;30(12):1591–1601. 10.1002/mds.26424. [DOI] [PubMed] [Google Scholar]
2. Goldman JG, Postuma R. Premotor and nonmotor features of Parkinson's disease. Curr Opin Neurol 2014;27(4):434–441. 10.1097/WCO.0000000000000112. [DOI] [PMC free article] [PubMed] [Google Scholar]
3. Ross GW, Abbott RD, Petrovitch H, Tanner CM, White LR. Pre‐motor features of Parkinson's disease: the Honolulu‐Asia aging study experience. Parkinsonism Relat Disord 2012;18:S199–S202. 10.1016/S1353-8020(11)70062-1. [DOI] [PubMed] [Google Scholar]
4. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease: MDS criteria for prodromal PD. Mov Disord 2015;30(12):1600–1611. 10.1002/mds.26431. [DOI] [PubMed] [Google Scholar]
5. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol 2021;20(5):385–397. 10.1016/S1474-4422(21)00030-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
6. Teive HAG, Bertucci Filho DC, Munhoz RP. Unusual motor and non‐motor symptoms and signs in the early stage of Parkinson's disease. Arq Neuropsiquiatr 2016;74(10):781–784. 10.1590/0004-282X20160126. [DOI] [PubMed] [Google Scholar]
7. de Lau LML, Koudstaal PJ, Hofman A, Breteler MMB. Subjective complaints precede Parkinson disease: the Rotterdam study. Arch Neurol 2006;63(3):362–365. 10.1001/archneur.63.3.noc50312. [DOI] [PubMed] [Google Scholar]
8. Gaenslen A, Swid I, Liepelt‐Scarfone I, Godau J, Berg D. The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease: perception of prodromal symptoms in PD. Mov Disord 2011;26(4):653–658. 10.1002/mds.23499. [DOI] [PMC free article] [PubMed] [Google Scholar]
9. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB, the MDS Task Force on the Definition of Parkinson's Disease . Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord 2019;34(10):1464–1470. 10.1002/mds.27802. [DOI] [PubMed] [Google Scholar]
10. Mahlknecht P, Marini K, Werkmann M, Poewe W, Seppi K. Prodromal Parkinson's disease: hype or hope for disease‐modification trials? Transl Neurodegener 2022;11(1):11. 10.1186/s40035-022-00286-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
11. Mercieca‐Bebber R, King MT, Calvert MJ, Stockler MR, Friedlander M. The importance of patient‐reported outcomes in clinical trials and strategies for future optimization. Patient Relat Outcome Meas 2018;9:353–367. 10.2147/PROM.S156279. [DOI] [PMC free article] [PubMed] [Google Scholar]
12. Peters MDJ, Godfrey C, McInerney P, Munn Z, Tricco AC, Khalil H. Chapter 11: Scoping reviews. JBI Manual for Evidence Synthesis. Adelaide, South Australia: Joanna Briggs Institute; 2020. https://synthesismanual.jbi.global/. [Google Scholar]
13. Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA‐ScR): checklist and explanation. Ann Intern Med 2018;169(7):467–473. 10.7326/M18-0850. [DOI] [PubMed] [Google Scholar]
14. Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society‐sponsored revision of the unified Parkinson's disease rating scale (MDS‐UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008;23(15):2129–2170. 10.1002/mds.22340. [DOI] [PubMed] [Google Scholar]
15. Friederich A, Flinspach A, Suenkel U, et al. Prodromal features of Parkinson's disease: self‐reported symptoms versus clinically assessed signs. Mov Disord 2019;34(1):144–146. 10.1002/mds.27539. [DOI] [PubMed] [Google Scholar]
16. Fereshtehnejad SM, Yao C, Pelletier A, Montplaisir JY, Gagnon JF, Postuma RB. Evolution of prodromal Parkinson's disease and dementia with Lewy bodies: a prospective study. Brain 2019;142(7):2051–2067. 10.1093/brain/awz111. [DOI] [PubMed] [Google Scholar]
17. Liu SY, Zheng Z, Gu ZQ, et al. Prevalence of pre‐diagnostic symptoms did not differ between LRRK2‐related, GBA‐related and idiopathic patients with Parkinson's disease. Parkinsonism Relat Disord 2018;57:72–76. 10.1016/j.parkreldis.2018.08.007. [DOI] [PubMed] [Google Scholar]
18. Pont‐Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson's disease (the ONSET PDStudy): the onset PD study. Mov Disord 2015;30(2):229–237. 10.1002/mds.26077. [DOI] [PubMed] [Google Scholar]
19. Walter U, Kleinschmidt S, Rimmele F, Wunderlich C, Gemende I, Benecke R, Busse K. Potential impact of self‐perceived prodromal symptoms on the early diagnosis of Parkinson's disease. J Neurol 2013;260(12):3077–3085. 10.1007/s00415-013-7125-6. [DOI] [PubMed] [Google Scholar]
20. Flores‐Torres MH, Hughes KC, Molsberry S, et al. Cognitive function in men with non‐motor features of Parkinson's disease. BMJ Neurol Open 2021;3(1):e000112. 10.1136/bmjno-2020-000112. [DOI] [PMC free article] [PubMed] [Google Scholar]
21. Giorelli M, Bagnoli J, Consiglio L, Lopane M, Bosco Zimatore G, Zizza D, Difazio P. Do non‐motor symptoms in Parkinson's disease differ from essential tremor before initial diagnosis? A clinical and scintigraphic study. Parkinsonism Relat Disord 2014;20(1):17–21. 10.1016/j.parkreldis.2013.09.004. [DOI] [PubMed] [Google Scholar]
22. Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson's disease in primary care: a case‐control study. Lancet Neurol 2015;14(1):57–64. 10.1016/S1474-4422(14)70287-X. [DOI] [PubMed] [Google Scholar]
23. Schrag A, Zhelev SS, Hotham S, Merritt RD, Khan K, Graham L. Heterogeneity in progression of prodromal features in Parkinson's disease. Parkinsonism Relat Disord 2019;64:275–279. 10.1016/j.parkreldis.2019.05.013. [DOI] [PubMed] [Google Scholar]
24. Rodríguez‐Violante M, de Saráchaga AJ, Cervantes‐Arriaga A, et al. Self‐perceived pre‐motor symptoms load in patients with Parkinson's disease: a retrospective study. J Parkinsons Dis 2016;6(1):183–190. 10.3233/JPD-150705. [DOI] [PubMed] [Google Scholar]
25. Plouvier AOA, Olde Hartman TC, Boots LPW, Bloem BR, van Weel C, Lagro‐Janssen ALM. Time intervals in diagnosing Parkinson's disease: the patients' views. Patient Educ Couns 2015;98(6):777–782. 10.1016/j.pec.2015.02.010. [DOI] [PubMed] [Google Scholar]
26. Ongre SO, Larsen JP, Tysnes OB, Herlofson K. Fatigue in early Parkinson's disease: the Norwegian ParkWest study. Eur J Neurol 2017;24(1):105–111. 10.1111/ene.13161. [DOI] [PubMed] [Google Scholar]
27. Bae HJ, Cheon SM, Kim JW. Orthostatic hypotension in drug‐Naïve patients with Parkinson's disease. J Mov Disord 2011;4(1):33–37. 10.14802/jmd.11005. [DOI] [PMC free article] [PubMed] [Google Scholar]
28. Liu H, Ou R, Wei Q, Hou Y, Cao B, Zhao B, Shang H. Rapid eye movement behavior disorder in drug‐naïve patients with Parkinson's disease. J Clin Neurosci 2019;59:254–258. 10.1016/j.jocn.2018.07.007. [DOI] [PubMed] [Google Scholar]
29. Serra MC, Landry A, Juncos JL, et al. Increased odds of bladder and bowel symptoms in early Parkinson's disease. Neurourol Urodyn 2018;37(4):1344–1348. 10.1002/nau.23443. [DOI] [PMC free article] [PubMed] [Google Scholar]
30. Erro R, Picillo M, Vitale C, et al. Non‐motor symptoms in early Parkinson's disease: a 2‐year follow‐up study on previously untreated patients. J Neurol Neurosurg Psychiatry 2013;84(1):14–17. 10.1136/jnnp-2012-303419. [DOI] [PubMed] [Google Scholar]
31. Weintraub D, Simuni T, Caspell‐Garcia C, et al. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease: cognition and Nps in early Pd. Mov Disord 2015;30(7):919–927. 10.1002/mds.26170. [DOI] [PMC free article] [PubMed] [Google Scholar]
32. Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the apathy evaluation scale. Psychiatry Res 1991;38(2):143–162. 10.1016/0165-1781(91)90040-v. [DOI] [PubMed] [Google Scholar]
33. Chaudhuri K, Pal S, DiMarco A, et al. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry 2002;73(6):629–635. 10.1136/jnnp.73.6.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
34. Santangelo G, Barone P, Cuoco S, et al. Apathy in untreated, de novo patients with Parkinson's disease: validation study of apathy evaluation scale. J Neurol 2014;261(12):2319–2328. 10.1007/s00415-014-7498-1. [DOI] [PubMed] [Google Scholar]
35. Orso B, Famà F, Giorgetti L, et al. Polysomnographic correlates of sleep disturbances in de novo, drug naïve Parkinson's disease. Neurol Sci 2022;43(4):2531–2536. 10.1007/s10072-021-05622-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
36. Tosin MHS, Simuni T, Stebbins GT, Cedarbaum JM. Tracking emergence of new motor and non‐motor symptoms using the MDS‐UPDRS: a novel outcome measure for early Parkinson's disease? J Parkinsons Dis 2022;12(4):1345–1351. 10.3233/JPD-223170. [DOI] [PMC free article] [PubMed] [Google Scholar]
37. Zimmermann M, Gaenslen A, Prahl K, et al. Patient's perception: shorter and more severe prodromal phase in GBA ‐associated PD. Eur J Neurol 2019;26(4):694–698. 10.1111/ene.13776. [DOI] [PubMed] [Google Scholar]
38. Pont‐Sunyer C, Tolosa E, Caspell‐Garcia C, et al. The prodromal phase of leucine‐rich repeat kinase 2‐associated Parkinson disease: clinical and imaging studies: prodromal characterization of LRRK2 PD. Mov Disord 2017;32(5):726–738. 10.1002/mds.26964. [DOI] [PubMed] [Google Scholar]
39. Maraki MI, Stefanis L, Yannakoulia M, et al. Motor function and the probability of prodromal Parkinson's disease in older adults. Mov Disord 2019;34(9):1345–1353. 10.1002/mds.27792. [DOI] [PubMed] [Google Scholar]
40. Sung HY, Park JW, Kim JS. The frequency and severity of gastrointestinal symptoms in patients with early Parkinson's disease. J Mov Disord 2014;7(1):7–12. 10.14802/jmd.14002. [DOI] [PMC free article] [PubMed] [Google Scholar]
41. Uchiyama T, Sakakibara R, Yamamoto T, et al. Urinary dysfunction in early and untreated Parkinson's disease. J Neurol Neurosurg Psychiatry 2011;82(12):1382–1386. 10.1136/jnnp.2011.241075. [DOI] [PubMed] [Google Scholar]
42. Swaminath PV, Ragothaman M, Koshy S, et al. Urogenital symptoms in Parkinson's disease and multiple system atrophy‐parkinsonism: At onset and later. J Assoc Physicians India 2010;58:86–90. [PubMed] [Google Scholar]
43. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14(6):540–545. 10.1093/sleep/14.6.540. [DOI] [PubMed] [Google Scholar]
44. Sixel‐Döring F, Schweitzer M, Mollenhauer B, Trenkwalder C. Intraindividual variability of REM sleep behavior disorder in Parkinson's disease: a comparative assessment using a new REM sleep behavior disorder severity scale (RBDSS) for clinical routine. J Clin Sleep Med 2011;7(1):75–80. [PMC free article] [PubMed] [Google Scholar]
45. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982;17(1):37–49. 10.1016/0022-3956(82)90033-4. [DOI] [PubMed] [Google Scholar]
46. Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ. Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA‐AUT. Mov Disord 2004;19(11):1306–1312. 10.1002/mds.20153. [DOI] [PubMed] [Google Scholar]
47. Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 1984;32(3):489–502. 10.1016/0031-9384(84)90269-5. [DOI] [PubMed] [Google Scholar]
48. Chaudhuri KR, Martinez‐Martin P, Schapira AHV, et al. International multicenter pilot study of the first comprehensive self‐completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study. Mov Disord 2006;21(7):916–923. 10.1002/mds.20844. [DOI] [PubMed] [Google Scholar]
49. Beck AT, Steer RA, Carbin MG. Psychometric properties of the Beck depression inventory: twenty‐five years of evaluation. Clin Psychol Rev 1988;8(1):77–100. 10.1016/0272-7358(88)90050-5. [DOI] [Google Scholar]
50. Wenning GK, Tison F, Seppi K, et al. Development and validation of the unified multiple system atrophy rating scale (UMSARS). Mov Disord 2004;19(12):1391–1402. 10.1002/mds.20255. [DOI] [PubMed] [Google Scholar]
51. Doty RL, Marcus A, Lee WW. Development of the 12‐item cross‐cultural smell identification test (CC‐SIT). Laryngoscope 1996;106(3 Pt 1):353–356. 10.1097/00005537-199603000-00021. [DOI] [PubMed] [Google Scholar]
52. Chaudhuri KR, Martinez‐Martin P, Brown RG, et al. The metric properties of a novel non‐motor symptoms scale for Parkinson's disease: results from an international pilot study. Mov Disord 2007;22(13):1901–1911. 10.1002/mds.21596. [DOI] [PubMed] [Google Scholar]
53. Olszewska DA, Fearon C, Lynch T. Loss of visual feedback revealing motor impairment – an early symptom of Parkinson's disease in two Irish farmers. J Clin Mov Disord 2016;3(1):12. 10.1186/s40734-016-0040-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
54. Kresojević N, Janković M, Petrović I, et al. Presenting symptoms of GBA‐related Parkinson's disease. Parkinsonism Relat Disord 2015;21(7):804–807. 10.1016/j.parkreldis.2015.04.028. [DOI] [PubMed] [Google Scholar]
55. Kang KW, Choi SM, Kim BC. Gender differences in motor and non‐motor symptoms in early Parkinson disease. Medicine (Baltimore) 2022;101(3):e28643. 10.1097/MD.0000000000028643. [DOI] [PMC free article] [PubMed] [Google Scholar]
56. Picillo M, Erro R, Amboni M, et al. Gender differences in non‐motor symptoms in early Parkinson's disease: a 2‐years follow‐up study on previously untreated patients. Parkinsonism Relat Disord 2014;20(8):850–854. 10.1016/j.parkreldis.2014.04.023. [DOI] [PubMed] [Google Scholar]
57. Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, Hyman N. The Parkinson's disease questionnaire (PDQ‐39): development and validation of a Parkinson's disease summary index score. Age Ageing 1997;26(5):353–357. 10.1093/ageing/26.5.353. [DOI] [PubMed] [Google Scholar]
58. Krupp LB, LaRocca NG, Muir‐Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989;46(10):1121–1123. 10.1001/archneur.1989.00520460115022. [DOI] [PubMed] [Google Scholar]
59. Kaufer DI, Cummings JL, Ketchel P, et al. Validation of the NPI‐Q, a brief clinical form of the neuropsychiatric inventory. J Neuropsychiatry Clin Neurosci 2000;12(2):233–239. 10.1176/jnp.12.2.233. [DOI] [PubMed] [Google Scholar]
60. Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386(9996):896–912. 10.1016/S0140-6736(14)61393-3. [DOI] [PubMed] [Google Scholar]
61. Müller B, Larsen JP, Wentzel‐Larsen T, Skeie GO, Tysnes OB, Group for TPS . Autonomic and sensory symptoms and signs in incident, untreated Parkinson's disease: frequent but mild. Mov Disord 2011;26(1):65–72. 10.1002/mds.23387. [DOI] [PubMed] [Google Scholar]
62. Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AFG, Rodriguez‐Violante M, Schrag A. The neuropsychiatry of Parkinson's disease: advances and challenges. Lancet Neurol 2022;21(1):89–102. 10.1016/S1474-4422(21)00330-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
63. Mammen JR, Speck RM, Stebbins GT, et al. Relative meaningfulness and impacts of symptoms in people with early‐stage Parkinson's disease. J Parkinsons Dis 2023;13(4):619–632. 10.3233/JPD-225068. [DOI] [PMC free article] [PubMed] [Google Scholar]
64. Miller‐Patterson C, Hsu JY, Willis AW, Hamedani AG. Functional impairment in individuals with prodromal or unrecognized Parkinson disease. JAMA Neurol 2023;80(2):200. 10.1001/jamaneurol.2022.4621. [DOI] [PMC free article] [PubMed] [Google Scholar]
65. Li J, Grimes K, Saade J, et al. Development of a simplified smell test to identify patients with typical Parkinson's as informed by multiple cohorts, machine learning and external validation. medRxiv 2024. 10.1101/2024.08.09.24311696. [DOI] [Google Scholar]
66. de Andrade DC, Mylius V, Perez‐Lloret S, et al. Pain in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them. Pain 2023;164(11):2425–2434. 10.1097/j.pain.0000000000002968. [DOI] [PubMed] [Google Scholar]
67. Tseng MT, Lin CH. Pain in early‐stage Parkinson's disease: implications from clinical features to pathophysiology mechanisms. J Formos Med Assoc 2017;116(8):571–581. 10.1016/j.jfma.2017.04.024. [DOI] [PubMed] [Google Scholar]
68. Rothrock NE, Kaiser KA, Cella D. Developing a valid patient‐reported outcome measure. Clin Pharmacol Ther 2011;90(5):737–742. 10.1038/clpt.2011.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
69. Mestre TA, Stebbins GT, Stephenson D, et al. Patient‐centered development of clinical outcome assessments in early Parkinson disease: key priorities and advances. npj Park Dis 2024;10(1):101. 10.1038/s41531-024-00716-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
70. Martinez‐Martin P, Leentjens AFG, de Pedro‐Cuesta J, Chaudhuri KR, Schrag AE, Weintraub D. Accuracy of screening instruments for detection of neuropsychiatric syndromes in Parkinson's disease. Mov Disord 2016;31(3):270–279. 10.1002/mds.26522. [DOI] [PubMed] [Google Scholar]
71. Zolfaghari S, Thomann AE, Lewandowski N, et al. Self‐report versus clinician examination in early Parkinson's disease. Mov Disord 2022;37(3):585–597. 10.1002/mds.28884. [DOI] [PMC free article] [PubMed] [Google Scholar]
72. Staunton H, Kelly K, Newton L, et al. A patient‐centered conceptual model of symptoms and their impact in early Parkinson's disease: a qualitative study. J Parkinsons Dis 2022;12(1):137–151. 10.3233/JPD-202457. [DOI] [PMC free article] [PubMed] [Google Scholar]
73. Regnault A, Boroojerdi B, Meunier J, Bani M, Morel T, Cano S. Does the MDS‐UPDRS provide the precision to assess progression in early Parkinson's disease? Learnings from the Parkinson's progression marker initiative cohort. J Neurol 2019;266(8):1927–1936. 10.1007/s00415-019-09348-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
74. Holden SK, Finseth T, Sillau SH, Berman BD. Progression of MDS‐UPDRS scores over five years in De novo Parkinson disease from the Parkinson's progression markers initiative cohort. Mov Disord Clin Pract 2018;5(1):47–53. 10.1002/mdc3.12553. [DOI] [PMC free article] [PubMed] [Google Scholar]
75. van Wamelen DJ, Martinez‐Martin P, Weintraub D, et al. The non‐motor symptoms scale in Parkinson's disease: validation and use. Acta Neurol Scand 2021;143(1):3–12. 10.1111/ane.13336. [DOI] [PubMed] [Google Scholar]
76. Haaxma CA, Bloem BR, Borm GF, et al. Gender differences in Parkinson's disease. J Neurol Neurosurg Psychiatry 2007;78(8):819–824. 10.1136/jnnp.2006.103788. [DOI] [PMC free article] [PubMed] [Google Scholar]
77. Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009;361(17):1651–1661. 10.1056/NEJMoa0901281. [DOI] [PMC free article] [PubMed] [Google Scholar]
78. Healy DG, Falchi M, O'Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2‐associated Parkinson's disease: a case‐control study. Lancet Neurol 2008;7(7):583–590. 10.1016/S1474-4422(08)70117-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
79. ODP . Pathways to Prevention P2P | Prevention Research; Accessed December 6, 2024. https://prevention.nih.gov/research-priorities/research-needs-and-gaps/pathways-prevention.
80. Up H. EJS‐ACT PD . Cure Parkinson's; 2021. Accessed December 6, 2024. https://cureparkinsons.org.uk/2021/06/actpd/.

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix S1. Research strategy (MEDLINE).

Table S1. Included studies and population demographics.

Table S2. List of extracted reported symptoms for each standardized reported symptom (SRS) and tools used to measure the symptoms.

MDC3-12-721-s001.docx^{(74.1KB, docx)}

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

[mdc370007-bib-0001] 1. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease: MDS‐PD Clinical Diagnostic Criteria. Mov Disord 2015;30(12):1591–1601. 10.1002/mds.26424. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0002] 2. Goldman JG, Postuma R. Premotor and nonmotor features of Parkinson's disease. Curr Opin Neurol 2014;27(4):434–441. 10.1097/WCO.0000000000000112. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0003] 3. Ross GW, Abbott RD, Petrovitch H, Tanner CM, White LR. Pre‐motor features of Parkinson's disease: the Honolulu‐Asia aging study experience. Parkinsonism Relat Disord 2012;18:S199–S202. 10.1016/S1353-8020(11)70062-1. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0004] 4. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson's disease: MDS criteria for prodromal PD. Mov Disord 2015;30(12):1600–1611. 10.1002/mds.26431. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0005] 5. Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson's disease. Lancet Neurol 2021;20(5):385–397. 10.1016/S1474-4422(21)00030-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0006] 6. Teive HAG, Bertucci Filho DC, Munhoz RP. Unusual motor and non‐motor symptoms and signs in the early stage of Parkinson's disease. Arq Neuropsiquiatr 2016;74(10):781–784. 10.1590/0004-282X20160126. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0007] 7. de Lau LML, Koudstaal PJ, Hofman A, Breteler MMB. Subjective complaints precede Parkinson disease: the Rotterdam study. Arch Neurol 2006;63(3):362–365. 10.1001/archneur.63.3.noc50312. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0008] 8. Gaenslen A, Swid I, Liepelt‐Scarfone I, Godau J, Berg D. The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease: perception of prodromal symptoms in PD. Mov Disord 2011;26(4):653–658. 10.1002/mds.23499. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0009] 9. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB, the MDS Task Force on the Definition of Parkinson's Disease . Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord 2019;34(10):1464–1470. 10.1002/mds.27802. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0010] 10. Mahlknecht P, Marini K, Werkmann M, Poewe W, Seppi K. Prodromal Parkinson's disease: hype or hope for disease‐modification trials? Transl Neurodegener 2022;11(1):11. 10.1186/s40035-022-00286-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0011] 11. Mercieca‐Bebber R, King MT, Calvert MJ, Stockler MR, Friedlander M. The importance of patient‐reported outcomes in clinical trials and strategies for future optimization. Patient Relat Outcome Meas 2018;9:353–367. 10.2147/PROM.S156279. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0012] 12. Peters MDJ, Godfrey C, McInerney P, Munn Z, Tricco AC, Khalil H. Chapter 11: Scoping reviews. JBI Manual for Evidence Synthesis. Adelaide, South Australia: Joanna Briggs Institute; 2020. https://synthesismanual.jbi.global/. [Google Scholar]

[mdc370007-bib-0013] 13. Tricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA‐ScR): checklist and explanation. Ann Intern Med 2018;169(7):467–473. 10.7326/M18-0850. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0014] 14. Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society‐sponsored revision of the unified Parkinson's disease rating scale (MDS‐UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008;23(15):2129–2170. 10.1002/mds.22340. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0015] 15. Friederich A, Flinspach A, Suenkel U, et al. Prodromal features of Parkinson's disease: self‐reported symptoms versus clinically assessed signs. Mov Disord 2019;34(1):144–146. 10.1002/mds.27539. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0016] 16. Fereshtehnejad SM, Yao C, Pelletier A, Montplaisir JY, Gagnon JF, Postuma RB. Evolution of prodromal Parkinson's disease and dementia with Lewy bodies: a prospective study. Brain 2019;142(7):2051–2067. 10.1093/brain/awz111. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0017] 17. Liu SY, Zheng Z, Gu ZQ, et al. Prevalence of pre‐diagnostic symptoms did not differ between LRRK2‐related, GBA‐related and idiopathic patients with Parkinson's disease. Parkinsonism Relat Disord 2018;57:72–76. 10.1016/j.parkreldis.2018.08.007. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0018] 18. Pont‐Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson's disease (the ONSET PDStudy): the onset PD study. Mov Disord 2015;30(2):229–237. 10.1002/mds.26077. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0019] 19. Walter U, Kleinschmidt S, Rimmele F, Wunderlich C, Gemende I, Benecke R, Busse K. Potential impact of self‐perceived prodromal symptoms on the early diagnosis of Parkinson's disease. J Neurol 2013;260(12):3077–3085. 10.1007/s00415-013-7125-6. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0020] 20. Flores‐Torres MH, Hughes KC, Molsberry S, et al. Cognitive function in men with non‐motor features of Parkinson's disease. BMJ Neurol Open 2021;3(1):e000112. 10.1136/bmjno-2020-000112. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0021] 21. Giorelli M, Bagnoli J, Consiglio L, Lopane M, Bosco Zimatore G, Zizza D, Difazio P. Do non‐motor symptoms in Parkinson's disease differ from essential tremor before initial diagnosis? A clinical and scintigraphic study. Parkinsonism Relat Disord 2014;20(1):17–21. 10.1016/j.parkreldis.2013.09.004. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0022] 22. Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson's disease in primary care: a case‐control study. Lancet Neurol 2015;14(1):57–64. 10.1016/S1474-4422(14)70287-X. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0023] 23. Schrag A, Zhelev SS, Hotham S, Merritt RD, Khan K, Graham L. Heterogeneity in progression of prodromal features in Parkinson's disease. Parkinsonism Relat Disord 2019;64:275–279. 10.1016/j.parkreldis.2019.05.013. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0024] 24. Rodríguez‐Violante M, de Saráchaga AJ, Cervantes‐Arriaga A, et al. Self‐perceived pre‐motor symptoms load in patients with Parkinson's disease: a retrospective study. J Parkinsons Dis 2016;6(1):183–190. 10.3233/JPD-150705. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0025] 25. Plouvier AOA, Olde Hartman TC, Boots LPW, Bloem BR, van Weel C, Lagro‐Janssen ALM. Time intervals in diagnosing Parkinson's disease: the patients' views. Patient Educ Couns 2015;98(6):777–782. 10.1016/j.pec.2015.02.010. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0026] 26. Ongre SO, Larsen JP, Tysnes OB, Herlofson K. Fatigue in early Parkinson's disease: the Norwegian ParkWest study. Eur J Neurol 2017;24(1):105–111. 10.1111/ene.13161. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0027] 27. Bae HJ, Cheon SM, Kim JW. Orthostatic hypotension in drug‐Naïve patients with Parkinson's disease. J Mov Disord 2011;4(1):33–37. 10.14802/jmd.11005. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0028] 28. Liu H, Ou R, Wei Q, Hou Y, Cao B, Zhao B, Shang H. Rapid eye movement behavior disorder in drug‐naïve patients with Parkinson's disease. J Clin Neurosci 2019;59:254–258. 10.1016/j.jocn.2018.07.007. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0029] 29. Serra MC, Landry A, Juncos JL, et al. Increased odds of bladder and bowel symptoms in early Parkinson's disease. Neurourol Urodyn 2018;37(4):1344–1348. 10.1002/nau.23443. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0030] 30. Erro R, Picillo M, Vitale C, et al. Non‐motor symptoms in early Parkinson's disease: a 2‐year follow‐up study on previously untreated patients. J Neurol Neurosurg Psychiatry 2013;84(1):14–17. 10.1136/jnnp-2012-303419. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0031] 31. Weintraub D, Simuni T, Caspell‐Garcia C, et al. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease: cognition and Nps in early Pd. Mov Disord 2015;30(7):919–927. 10.1002/mds.26170. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0032] 32. Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the apathy evaluation scale. Psychiatry Res 1991;38(2):143–162. 10.1016/0165-1781(91)90040-v. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0033] 33. Chaudhuri K, Pal S, DiMarco A, et al. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry 2002;73(6):629–635. 10.1136/jnnp.73.6.629. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0034] 34. Santangelo G, Barone P, Cuoco S, et al. Apathy in untreated, de novo patients with Parkinson's disease: validation study of apathy evaluation scale. J Neurol 2014;261(12):2319–2328. 10.1007/s00415-014-7498-1. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0035] 35. Orso B, Famà F, Giorgetti L, et al. Polysomnographic correlates of sleep disturbances in de novo, drug naïve Parkinson's disease. Neurol Sci 2022;43(4):2531–2536. 10.1007/s10072-021-05622-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0036] 36. Tosin MHS, Simuni T, Stebbins GT, Cedarbaum JM. Tracking emergence of new motor and non‐motor symptoms using the MDS‐UPDRS: a novel outcome measure for early Parkinson's disease? J Parkinsons Dis 2022;12(4):1345–1351. 10.3233/JPD-223170. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0037] 37. Zimmermann M, Gaenslen A, Prahl K, et al. Patient's perception: shorter and more severe prodromal phase in GBA ‐associated PD. Eur J Neurol 2019;26(4):694–698. 10.1111/ene.13776. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0038] 38. Pont‐Sunyer C, Tolosa E, Caspell‐Garcia C, et al. The prodromal phase of leucine‐rich repeat kinase 2‐associated Parkinson disease: clinical and imaging studies: prodromal characterization of LRRK2 PD. Mov Disord 2017;32(5):726–738. 10.1002/mds.26964. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0039] 39. Maraki MI, Stefanis L, Yannakoulia M, et al. Motor function and the probability of prodromal Parkinson's disease in older adults. Mov Disord 2019;34(9):1345–1353. 10.1002/mds.27792. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0040] 40. Sung HY, Park JW, Kim JS. The frequency and severity of gastrointestinal symptoms in patients with early Parkinson's disease. J Mov Disord 2014;7(1):7–12. 10.14802/jmd.14002. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0041] 41. Uchiyama T, Sakakibara R, Yamamoto T, et al. Urinary dysfunction in early and untreated Parkinson's disease. J Neurol Neurosurg Psychiatry 2011;82(12):1382–1386. 10.1136/jnnp.2011.241075. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0042] 42. Swaminath PV, Ragothaman M, Koshy S, et al. Urogenital symptoms in Parkinson's disease and multiple system atrophy‐parkinsonism: At onset and later. J Assoc Physicians India 2010;58:86–90. [PubMed] [Google Scholar]

[mdc370007-bib-0043] 43. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14(6):540–545. 10.1093/sleep/14.6.540. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0044] 44. Sixel‐Döring F, Schweitzer M, Mollenhauer B, Trenkwalder C. Intraindividual variability of REM sleep behavior disorder in Parkinson's disease: a comparative assessment using a new REM sleep behavior disorder severity scale (RBDSS) for clinical routine. J Clin Sleep Med 2011;7(1):75–80. [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0045] 45. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982;17(1):37–49. 10.1016/0022-3956(82)90033-4. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0046] 46. Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ. Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA‐AUT. Mov Disord 2004;19(11):1306–1312. 10.1002/mds.20153. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0047] 47. Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 1984;32(3):489–502. 10.1016/0031-9384(84)90269-5. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0048] 48. Chaudhuri KR, Martinez‐Martin P, Schapira AHV, et al. International multicenter pilot study of the first comprehensive self‐completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study. Mov Disord 2006;21(7):916–923. 10.1002/mds.20844. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0049] 49. Beck AT, Steer RA, Carbin MG. Psychometric properties of the Beck depression inventory: twenty‐five years of evaluation. Clin Psychol Rev 1988;8(1):77–100. 10.1016/0272-7358(88)90050-5. [DOI] [Google Scholar]

[mdc370007-bib-0050] 50. Wenning GK, Tison F, Seppi K, et al. Development and validation of the unified multiple system atrophy rating scale (UMSARS). Mov Disord 2004;19(12):1391–1402. 10.1002/mds.20255. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0051] 51. Doty RL, Marcus A, Lee WW. Development of the 12‐item cross‐cultural smell identification test (CC‐SIT). Laryngoscope 1996;106(3 Pt 1):353–356. 10.1097/00005537-199603000-00021. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0052] 52. Chaudhuri KR, Martinez‐Martin P, Brown RG, et al. The metric properties of a novel non‐motor symptoms scale for Parkinson's disease: results from an international pilot study. Mov Disord 2007;22(13):1901–1911. 10.1002/mds.21596. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0053] 53. Olszewska DA, Fearon C, Lynch T. Loss of visual feedback revealing motor impairment – an early symptom of Parkinson's disease in two Irish farmers. J Clin Mov Disord 2016;3(1):12. 10.1186/s40734-016-0040-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0054] 54. Kresojević N, Janković M, Petrović I, et al. Presenting symptoms of GBA‐related Parkinson's disease. Parkinsonism Relat Disord 2015;21(7):804–807. 10.1016/j.parkreldis.2015.04.028. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0055] 55. Kang KW, Choi SM, Kim BC. Gender differences in motor and non‐motor symptoms in early Parkinson disease. Medicine (Baltimore) 2022;101(3):e28643. 10.1097/MD.0000000000028643. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0056] 56. Picillo M, Erro R, Amboni M, et al. Gender differences in non‐motor symptoms in early Parkinson's disease: a 2‐years follow‐up study on previously untreated patients. Parkinsonism Relat Disord 2014;20(8):850–854. 10.1016/j.parkreldis.2014.04.023. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0057] 57. Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, Hyman N. The Parkinson's disease questionnaire (PDQ‐39): development and validation of a Parkinson's disease summary index score. Age Ageing 1997;26(5):353–357. 10.1093/ageing/26.5.353. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0058] 58. Krupp LB, LaRocca NG, Muir‐Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989;46(10):1121–1123. 10.1001/archneur.1989.00520460115022. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0059] 59. Kaufer DI, Cummings JL, Ketchel P, et al. Validation of the NPI‐Q, a brief clinical form of the neuropsychiatric inventory. J Neuropsychiatry Clin Neurosci 2000;12(2):233–239. 10.1176/jnp.12.2.233. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0060] 60. Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386(9996):896–912. 10.1016/S0140-6736(14)61393-3. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0061] 61. Müller B, Larsen JP, Wentzel‐Larsen T, Skeie GO, Tysnes OB, Group for TPS . Autonomic and sensory symptoms and signs in incident, untreated Parkinson's disease: frequent but mild. Mov Disord 2011;26(1):65–72. 10.1002/mds.23387. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0062] 62. Weintraub D, Aarsland D, Chaudhuri KR, Dobkin RD, Leentjens AFG, Rodriguez‐Violante M, Schrag A. The neuropsychiatry of Parkinson's disease: advances and challenges. Lancet Neurol 2022;21(1):89–102. 10.1016/S1474-4422(21)00330-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0063] 63. Mammen JR, Speck RM, Stebbins GT, et al. Relative meaningfulness and impacts of symptoms in people with early‐stage Parkinson's disease. J Parkinsons Dis 2023;13(4):619–632. 10.3233/JPD-225068. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0064] 64. Miller‐Patterson C, Hsu JY, Willis AW, Hamedani AG. Functional impairment in individuals with prodromal or unrecognized Parkinson disease. JAMA Neurol 2023;80(2):200. 10.1001/jamaneurol.2022.4621. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0065] 65. Li J, Grimes K, Saade J, et al. Development of a simplified smell test to identify patients with typical Parkinson's as informed by multiple cohorts, machine learning and external validation. medRxiv 2024. 10.1101/2024.08.09.24311696. [DOI] [Google Scholar]

[mdc370007-bib-0066] 66. de Andrade DC, Mylius V, Perez‐Lloret S, et al. Pain in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them. Pain 2023;164(11):2425–2434. 10.1097/j.pain.0000000000002968. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0067] 67. Tseng MT, Lin CH. Pain in early‐stage Parkinson's disease: implications from clinical features to pathophysiology mechanisms. J Formos Med Assoc 2017;116(8):571–581. 10.1016/j.jfma.2017.04.024. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0068] 68. Rothrock NE, Kaiser KA, Cella D. Developing a valid patient‐reported outcome measure. Clin Pharmacol Ther 2011;90(5):737–742. 10.1038/clpt.2011.195. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0069] 69. Mestre TA, Stebbins GT, Stephenson D, et al. Patient‐centered development of clinical outcome assessments in early Parkinson disease: key priorities and advances. npj Park Dis 2024;10(1):101. 10.1038/s41531-024-00716-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0070] 70. Martinez‐Martin P, Leentjens AFG, de Pedro‐Cuesta J, Chaudhuri KR, Schrag AE, Weintraub D. Accuracy of screening instruments for detection of neuropsychiatric syndromes in Parkinson's disease. Mov Disord 2016;31(3):270–279. 10.1002/mds.26522. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0071] 71. Zolfaghari S, Thomann AE, Lewandowski N, et al. Self‐report versus clinician examination in early Parkinson's disease. Mov Disord 2022;37(3):585–597. 10.1002/mds.28884. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0072] 72. Staunton H, Kelly K, Newton L, et al. A patient‐centered conceptual model of symptoms and their impact in early Parkinson's disease: a qualitative study. J Parkinsons Dis 2022;12(1):137–151. 10.3233/JPD-202457. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0073] 73. Regnault A, Boroojerdi B, Meunier J, Bani M, Morel T, Cano S. Does the MDS‐UPDRS provide the precision to assess progression in early Parkinson's disease? Learnings from the Parkinson's progression marker initiative cohort. J Neurol 2019;266(8):1927–1936. 10.1007/s00415-019-09348-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0074] 74. Holden SK, Finseth T, Sillau SH, Berman BD. Progression of MDS‐UPDRS scores over five years in De novo Parkinson disease from the Parkinson's progression markers initiative cohort. Mov Disord Clin Pract 2018;5(1):47–53. 10.1002/mdc3.12553. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0075] 75. van Wamelen DJ, Martinez‐Martin P, Weintraub D, et al. The non‐motor symptoms scale in Parkinson's disease: validation and use. Acta Neurol Scand 2021;143(1):3–12. 10.1111/ane.13336. [DOI] [PubMed] [Google Scholar]

[mdc370007-bib-0076] 76. Haaxma CA, Bloem BR, Borm GF, et al. Gender differences in Parkinson's disease. J Neurol Neurosurg Psychiatry 2007;78(8):819–824. 10.1136/jnnp.2006.103788. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0077] 77. Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009;361(17):1651–1661. 10.1056/NEJMoa0901281. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0078] 78. Healy DG, Falchi M, O'Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2‐associated Parkinson's disease: a case‐control study. Lancet Neurol 2008;7(7):583–590. 10.1016/S1474-4422(08)70117-0. [DOI] [PMC free article] [PubMed] [Google Scholar]

[mdc370007-bib-0079] 79. ODP . Pathways to Prevention P2P | Prevention Research; Accessed December 6, 2024. https://prevention.nih.gov/research-priorities/research-needs-and-gaps/pathways-prevention.

[mdc370007-bib-0080] 80. Up H. EJS‐ACT PD . Cure Parkinson's; 2021. Accessed December 6, 2024. https://cureparkinsons.org.uk/2021/06/actpd/.

PERMALINK

Reported Symptoms in Prodromal and Early Motor Parkinson's Disease: A Scoping Review on the Patient Perspective

Joseph Saade, MD

Alice van Wyk, BS

Glenn T Stebbins, PhD

Tiago A Mestre, MD, PhD

Abstract

Background

Objective

Methods

Results

Conclusion

Methods

Inclusion/Exclusion Criteria

Search Strategy

Screening Process

FIG. 1.

Data Extraction

Data Analyses

Results

Description of Included Studies

Individual Experiences at Prodromal and Early Motor Stages of PD

FIG. 2.

Patient‐Reported Measures

FIG. 3.

Population‐Specific Characteristics

Toward a Conceptual Framework for the Earliest Lived Experiences in PD

Symptom Domains

Dysautonomia

TABLE 1.

Motor

Sensory

Behavioral

Cognitive

FIG. 4.

Sleep

Miscellaneous

Function Domains

ADL

Communication

Social Impairment

Sexual Impairment

Domain‐Specific Patient‐Reported Changes

A Conceptual Model of the Earliest Lived Experiences in PD

Measurement Tools for the Earliest Lived Experiences in PD

Limitations

Conclusion

Author Role

Disclosures

Supporting information

Acknowledgments

Data Availability Statement

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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Links to NCBI Databases