Abstract
Background and Objectives
In preparation for future clinical trials involving individuals with Alzheimer disease (AD), mild cognitive impairment (MCI), and dementia, it is important to ascertain the widespread impact of symptoms from the direct perspectives of patients and caregivers. In this study, we performed cross-sectional surveys using large-scale patient and caregiver data to identify the prevalence and average impact of symptoms and symptomatic themes experienced by adults with AD, MCI, and dementia. Subsequent analyses were used to determine which demographic and disease-specific factors are associated with more severe disease.
Methods
Fifteen adults with AD (6), MCI (8), and dementia (1) and 15 caregivers of adults with AD (7), MCI (6), and dementia (2) participated in qualitative interviews providing 1,166 and 1,097 unique quotes pertaining to symptom burden. Using open-ended questions from a comprehensive interview guide, participants were asked to identify the symptoms of AD that have the greatest effect on their lives or the lives of the individual for whom they provide care. A cross-sectional survey was then implemented inquiring about the potential symptoms of importance identified during preliminary qualitative interviews. Four-hundred thirty-three individuals (patients and caregivers) participated in the cross-sectional survey, providing more than 35,000 symptom rating responses. Subsequent analyses were conducted to determine how demographic and disease-specific characteristics correlate with symptomatic theme prevalence.
Results
The most frequent symptomatic themes reported by individuals with AD, MCI, and dementia in the cross-sectional survey were memory problems (99.0%), problems thinking (90.3%), and communication difficulties (80.4%). Patients identified decreased satisfaction in social situations (1.45), fatigue (1.45), and memory problems (1.41) as the most impactful symptomatic themes (range 0–4). Patient-reported symptomatic theme prevalence was strongly associated with the Modified Rankin Scale (mRS) for neurologic disability.
Discussion
Individuals with AD, MCI, and dementia experience a variety of symptoms that significantly affect their daily lives. These symptoms, many underrecognized, are of variable importance to individuals with these diseases and may inform potential targets for future therapeutic intervention as well as facilitate the development and validation of disease-specific outcome measures.
Introduction
Nearly 7 million Americans aged 65 and older have Alzheimer disease, a debilitating condition causing significant burden to patients and their families.1 Alzheimer disease (AD) is the leading cause of dementia accounting for 60%–80% of cases. Almost 2/3 of Americans with AD are women in part due to a higher survival rate than men and age being an important risk factor for developing AD. In addition, a higher prevalence of cardiovascular disease in women aged older than 60 is another contributing factor to a higher likelihood of dementia and AD in women.1 The cardinal signs and symptoms of AD include memory deficits, cognitive impairment, difficulty completing routine daily activities, impaired judgement, and alterations to mood, personality, and behaviors.2,3 Mild cognitive impairment (MCI), a milder disease characterized by abnormal cognitive decline, is a known risk factor for developing AD or a related dementia.4 An estimated 15% of those with MCI develop dementia after 2 years. Although AD and MCI are most commonly associated with impaired memory and cognition, patients also experience a range of physical, social, and emotional symptoms that impair their daily functioning.5,6 As novel therapies are tested in individuals with AD, MCI, or dementia, it is crucial to better understand the symptoms and areas of health that have the greatest impact on the lives of those living with these diseases. In this study, we conducted semistructured interviews to develop a survey to use in a cross-sectional study to obtain large-scale patient-reported and caregiver-reported data identifying the most prevalent and burdensome symptoms to those living with AD, MCI, or dementia.
Methods
Participants
Study participants were individuals aged 18 years and older with a self-reported diagnosis of AD, MCI, or dementia and individuals aged 18 years and older who care for someone with AD, MCI, or dementia. Qualitative interview participants were recruited in patient-caregiver pairs from the University of Rochester Memory Care Program, the University of Rochester Neurology Study Interest Registry, the University of Rochester Clinical Translational Science Institute Registry, and ResearchMatch.com. Cross-sectional study participants were recruited from the Banner Health Institute's Alzheimer's Prevention Registry.
Semistructured Qualitative Interviews
We conducted semistructured qualitative interviews with individuals with AD, MCI, or dementia and caregivers of individuals with AD, MCI, or dementia. All interviews were conducted over the phone and were audio-recorded using Zoom, a Health Insurance Portability and Accountability Act (HIPAA) compliant conferencing software. Using open-ended questions, we asked participants to identify the symptoms and areas of health that have the greatest impact on their life or the life of the individual for whom they care. All interview audio-recordings were transcribed, coded, and analyzed using a qualitative framework technique, triangulation, and an investigator consensus approach.7 We used recurring similar quotes among participants to identify potential symptoms of importance. Symptoms representing like concepts were grouped into symptomatic themes of AD-related, MCI-related, and dementia-related health. In addition, each symptomatic theme was categorized as a physical, mental, social, or disease-specific component of health in accordance with the World Health Organization's framework of health. A cross-sectional survey was then developed inquiring about the potential symptoms of importance identified during preliminary qualitative interviews.
National Online Cross-Sectional Study
Using the qualitative interview results, 2 surveys were developed and implemented in an online cross-sectional study of individuals with AD, MCI, or dementia and caregivers of individuals with AD, MCI, or dementia through the Banner Health Institute's Alzheimer's Prevention Registry. The surveys were administered electronically through REDCap, a HIPAA-compliant electronic data capture system. Two survey links, one for patients to complete and the other for caregivers, were distributed to eligible members of the Alzheimer's Prevention Registry. Participants were asked to read an information letter and complete a demographics questionnaire before completing the main survey.
Each of the surveys included demographic questions, clinical questions, and symptom-specific questions. The symptom-specific questions included potential symptoms of importance identified during our preliminary qualitative interviews, as well as symptoms of importance previously reported in other neurologic disease populations using the same methodology.8-22 Question selection for both surveys was conducted using an investigator consensus approach among our research team. Both surveys were designed to include all potential symptoms of importance while limiting question redundancy. For each individual symptom question on the survey, patients were asked “How much does the following impact your life now?” and caregivers were asked “How much does the following impact his/her life now?”. Participants provided responses using a 6-point Likert-type scale. The response options on both surveys consisted of the following: (1) I/They do not experience this. (2) I/They experience this but it does not affect my/their life. (3) It affects my/their life a little. (4) It affects my/their life moderately. (5) It affects my/their life very much. (6) It affects my/their life severely. On survey completion, participants were asked to list and rate the impact of any symptoms that were not included in the survey. This methodology has previously been implemented in studies of other neurologic disease populations.8-22
Standard Protocol Approvals, Registrations, and Participant Consents
This research conforms to the principles of the Declaration of Helsinki and was approved by the University of Rochester Research Subjects Review Board.
We obtained verbal informed consent from all semistructured interview participants. We obtained a waiver of documentation of consent for the cross-sectional study such that participants' acknowledgement of the study information letter and subsequent completion of the survey implied consent.
Statistical Analysis
Participants were included in the cross-sectional data analysis if they completed at least 1 demographic question and 1 survey question. We calculated the prevalence and average impact of each symptom and symptomatic theme for both the patient and caregiver sample cohorts. The average impact is a metric of the relative importance of a symptom to an individual and is measured on a 0 to 4 point scale. This metric was calculated from the scores of participants who stated that they or the individual they care for experiences the symptom or symptomatic theme (at any level of severity). Values were assigned to each survey response option as follows: 0 = the individual experiences the symptom but it does not affect the individual's life; 1 = the symptom affects the individual's life a little; 2 = the symptom affects the individual's life moderately; 3 = the symptom affects the individual's life very much; and 4 = the symptom affects the individual's life severely. In addition, the population impact score was calculated for each symptom and symptomatic theme assessed. This value was generated by multiplying the prevalence by the average impact of a symptom or symptomatic theme.8-22 Population impact scores also ranged from 0 to 4, 4 representing a symptom or symptomatic theme that affects all participants in the sample cohort severely.
For patients and caregivers, survey responses were categorized on the basis of age; sex; employment status (employment status changed because of their disease vs not); education status (college, master's/doctorate vs grade school, high school, technical degree); relationship status (married/in a registered partnership vs single, widowed, divorced, separated, or other); living situation (resides in the community [e.g., private home or apartment vs an independent living facility, assisted living facility, skilled nursing facility, or other]); diagnosis (AD vs MCI); genetic test positive for AD risk factor or variant (yes vs no); number of APOE4 copies (1 vs 2), a genetic variation where having 1 or 2 copies are known to increase the risk of AD; mobility status (walks independently with no assistive device vs uses assistive ambulatory device[s]); use of a home health aide (yes vs no); Modified Rankin Scale (mRS) for neurologic disability (no symptoms and no significant disability vs slight to severe disability)23; experiences seizures (yes vs no); years since first experienced problems thinking (above vs below the mean); and uses anti-anxiety medication (yes vs no). For the caregiver-reported data set, we also conducted 2 additional analyses based on the relationship of the participant to the affected individual (spouse/partner vs son/daughter, home health aide, other relative, or other).
We obtained descriptive statistics for the prevalence and average impact for each symptomatic theme assessed. We used Fisher exact tests to compare the prevalence of symptomatic themes across demographic subgroups. The Benjamini-Hochberg procedure was implemented for both the patient-reported and caregiver-reported data sets combined to correct for multiple comparisons. We used a false discovery rate of 0.05 and 180 test statistics and 0.05 and 187 test statistics for the patient-reported and caregiver-reported data sets, respectively. As outlined by this method, the p values were sorted from smallest to largest and the largest value of i such that p(i) ≤ 0.05 i/number of test statistics was determined. The null hypotheses associated with the p values p(1), …, p(i) were rejected, resulting in 8 i discoveries for the patient-reported data set and 50 i discoveries for the caregiver-reported data set.
Data Availability
Additional anonymized data not included in the article or supplemental files can be obtained through request to the corresponding author.
Results
Semistructured Qualitative Interviews
Thirty individuals participated in preliminary qualitative interviews (15 individuals with AD, MCI, or dementia and 15 caregivers). Twenty-six participants were enrolled as matched pairs (13 matched patient/caregiver pairs), and 4 participants were enrolled independently. We obtained 1,166 direct quotes from patients and 1,097 direct quotes from caregivers regarding the symptomatic burden of AD, MCI, or dementia. Each quote identified was coded as a unique symptom of AD health. When a participant with AD was asked, “What symptoms have the greatest impact on your quality of life or disease burden?”, adult participant with AD #4 replied, “Um, I guess I would say, um, short-term memory deficits”. A participant who was a caregiver to an individual with AD was asked, “What symptoms have the greatest impact on your spouse's quality of life or disease burden?” The caregiver of participant #7 replied, “He gets very frustrated when he can't remember things and do things”. This quote was coded as the symptoms, frustration, memory deficits, and inability to do things. The symptomatic themes most frequently identified by both patients and caregivers were cognitive impairment, mental health, and social role limitations. Patient and caregiver quotes were used to identify 194 and 173 symptoms of potential importance, respectively.
National Online Cross-sectional Study
The patient-reported survey consisted of 112 symptom questions representing 12 symptomatic themes. Participant responses were included in the data analysis if the participant completed at least 1 demographic question and 1 survey question. Of the 124 individuals with AD, MCI, or dementia who accessed the link, 104 met the inclusion criteria and were included in the data analysis. Individuals with AD, MCI, or dementia who completed the patient-reported survey ranged in age from 46 to 86 years, were mostly female (61.5%) and represented 34 US states. The patient-reported sample was predominantly individuals diagnosed with MCI (72.12%) followed by AD (15.38%). Only 4.8% of respondents reported having dementia. The caregiver-reported survey consisted of 99 symptom questions representing 11 symptomatic themes. Three-hundred fifty-seven caregivers accessed the link to participate in the caregiver-reported survey, and of these, 329 met inclusion criteria of completing at least 1 demographic and 1 survey question for data analysis. Study participants who completed the caregiver-reported survey ranged from 20 to 86 years of age were predominantly female (77.3%) and represented 46 US states. Over half of the caregiver-reported sample reported on individuals diagnosed with AD (58.36%). Nearly 15% of the caregivers reported on behalf of individuals with MCI and just over 15% of the sample consisted of individuals with dementia. Details regarding the demographic characteristics of the patient-reported sample cohort and the patient population reported on by caregivers are provided in Table 1. The demographic characteristics of the caregivers are provided in eTable 1.
Table 1.
Cross-Sectional Study Patient Demographic and Disease State Characteristics
| Patient-reported | Caregiver-reported | |
| Participants, no. | 104 | 329 |
| Age, y | ||
| Mean (SD) | 69.07 (7.46) | 80.09 (9.29) |
| Range | 46–86 | 53–103 |
| Sex, no. (%) | ||
| Female | 64 (61.54) | 190 (57.75) |
| Race, no. (%) | ||
| American Indian/Alaska Native | 1 (0.96) | 3 (0.91) |
| Asian | 1 (0.96) | 4 (1.22) |
| Black | 1 (0.96) | 6 (1.82) |
| White | 98 (94.23) | 307 (93.31) |
| Other | 2 (1.92) | 3 (0.91) |
| Hispanic/Latino, no. (%) | ||
| Yes | 1 (0.96) | 12 (3.65) |
| Employment status, no. (%) | ||
| Employed full-time | 6 (5.77) | 0 |
| Employed part-time | 2 (1.92) | 2 (0.61) |
| On disability | 8 (7.69) | 13 (3.95) |
| Not working/not on disability | 5 (4.81) | 30 (9.12) |
| Retired | 80 (76.92) | 275 (83.59) |
| Stay-a-home parent | 1 (0.96) | 3 (0.91) |
| Other/Omitted | 2 (1.92) | 6 (1.82) |
| Employment status changed due to disease, no. (%) | ||
| Yes | 21 (20.19) | 62 (18.84) |
| Highest level of education completed, no. (%) | ||
| Grade school | 1 (0.96) | 8 (2.43) |
| High school | 14 (13.46) | 117 (35.56) |
| Technical degree | 13 (12.50) | 27 (8.21) |
| College | 32 (30.77) | 84 (25.53) |
| Master's or doctorate | 43 (41.35) | 87 (26.44) |
| Omitted | 1 (0.96) | 4 (1.22) |
| Marital status, no. (%) | ||
| Married | 58 (55.77) | 190 (57.75) |
| Single | 9 (8.65) | 6 (1.82) |
| Widowed | 13 (12.50) | 104 (31.61) |
| Divorced | 20 (19.23) | 20 (6.08) |
| Separated | 1 (0.96) | 3 (0.91) |
| Registered partnership | 1 (0.96) | 2 (0.61) |
| Other/omitted | 1 (0.96) | 4 (1.22) |
| Living situation, no. (%) | ||
| Reside in the community | 94 (90.38) | 244 (74.16) |
| Independent living facility | 3 (2.88) | 13 (3.95) |
| Assisted living facility | 1 (0.96) | 33 (10.03) |
| Skilled nursing facility | 0 | 25 (7.60) |
| Other/omitted | 6 (5.77) | 14 (4.25) |
| Diagnosis, no. (%) | ||
| Alzheimer disease | 16 (15.38) | 192 (58.36) |
| Mild cognitive impairment | 75 (72.12) | 47 (14.29) |
| Vascular dementia | 2 (1.92) | 25 (7.60) |
| Dementia with Lewy bodies | 1 (0.96) | 9 (2.74) |
| Frontotemporal dementia | 2 (1.92) | 9 (2.74) |
| Parkinson disease dementia | 0 | 8 (2.43) |
| Positive genetic test associated with AD, no. (%) | ||
| Yes | 26 (25.00) | 30 (9.12) |
| Variant/genetic risk factor, no. (%) | ||
| APOE4 (1 copy) | 15 (14.42) | 9 (2.74) |
| APOE4 (2 copies) | 4 (3.85) | 4 (1.22) |
| PSEN1 | 0 | 1 (0.30) |
| I don't know/omitted | 81 (77.88) | 315 (95.74) |
| No genetic testing or was negative | 4 (3.85) | 0 |
| Medication use, no. (%) | ||
| Anti-anxiety medication | 10 (9.62) | 70 (21.28) |
| Anticonvulsants | 1 (0.96) | 2 (0.61) |
| NMDA antagonists | 8 (7.69) | 41 (12.46) |
| Antipsychotics | 0 | 31 (9.42) |
| Sleep aids | 6 (5.77) | 12 (3.65) |
| Does not take any of these listed | 1 (0.96) | 6 (1.82) |
| I don't know/omitted | 78 (75.00) | 157 (47.72) |
| Currently has a home health aide, no. (%) | ||
| Yes | 4 (3.85) | 77 (23.40) |
| Ability, no. (%) | ||
| No symptoms at all | 8 (7.69) | 0 |
| No significant disability | 49 (47.12) | 18 (5.47) |
| Slight disability | 28 (26.92) | 42 (12.77) |
| Moderate disability | 15 (14.42) | 132 (40.12) |
| Moderately severe disability | 3 (2.88) | 104 (31.61) |
| Severe disability | 0 | 32 (9.73) |
| Omitted | 1 (0.96) | 1 (0.30) |
| Number of years since first developed thinking problems | ||
| Mean (SD) | 5.92 (5.38) | 7.54 (5.73) |
| Range | 1–25 | 1–75 |
| Experiences seizures, no. (%) | ||
| Yes | 7 (6.73) | 13 (3.95) |
Prevalence of Symptoms and Symptomatic Themes
There were 2 symptomatic themes with a prevalence of 90% or greater among individuals with AD, MCI, or dementia who self-reported their symptoms. These were memory problems (99.0%) and problems thinking (90.3%). Details regarding the patient-reported prevalence of symptomatic themes are presented in Figure 1. The most prevalent self-reported individual symptoms in this sample cohort were memory loss (96.1%), forgetfulness (96.1%), impaired short-term memory (96.0%), and increased effort to remember things (96.0%). The patient-reported prevalence of all symptom questions assessed in the survey is provided in eTable 2.
Figure 1. Patient-Reported Symptomatic Theme Prevalence and Average Impact (n = 104).
Five symptomatic themes had a prevalence of 90.0% or greater among caregivers reporting on behalf of an individual with AD, MCI, or dementia. These were problems thinking (99.7%), memory problems (99.4%), impaired social interactions (95.4%), communication difficulties (93.6%), and fatigue (90.5%). Details regarding the caregiver-reported prevalence of symptomatic themes are presented in Figure 2. The most prevalent individual symptoms reported by caregivers were a decreased ability to think fast (99.1%), reduced decision-making abilities (98.7%), forgetfulness (98.7%), impaired short-term memory (98.7%), increased effort to remember things (98.7%), and difficulty locating items (98.7%). The caregiver-reported prevalence of all symptom questions assessed in the survey is provided in eTable 2.
Figure 2. Caregiver-Reported Symptomatic Theme Prevalence and Average Impact (n = 329).
Relative Importance of Symptoms and Symptomatic Themes
The symptomatic themes with the highest average impact score (0–4) as reported by individuals with AD, MCI, or dementia were decreased satisfaction in social situations (1.45), fatigue (1.45), and memory problems (1.41). Details regarding the patient-reported average impact score of symptomatic themes are presented in Figure 1. The individual symptoms with the highest average impact scores were impaired short-term memory (1.70), feeling worn out (1.68), and fear of progression of disease (1.57). The patient-reported average impact scores of all individual symptom questions are provided in eTable 2.
The symptomatic themes reported by caregivers as having the highest relative impact (0–4) on the individuals for whom they care were memory problems (3.07), problems thinking (2.75), and impaired social interactions (2.61). Details regarding the caregiver-reported average impact scores of symptomatic themes are presented in Figure 2. The individual symptoms that caregivers reported having the highest relative impact were difficulty managing bills (3.18), forgetfulness (3.02), and trouble using a computer (3.01). The caregiver-reported average impact scores of all symptom questions are provided in eTable 2. A comparison of patient-reported and caregiver-reported prevalence of symptoms shows caregivers reporting at a much higher rate than patients. Since patient and caregiver respondents are not matched, we cannot assert that these differences are due to variation in symptom perception.
Population Impact of Symptoms and Symptomatic Themes
Among individuals with AD, MCI or dementia, the symptomatic themes with the highest population impact score (0–4) were memory problems (1.40), problems thinking (1.11), and fatigue (1.07). The individual symptoms with the highest population impact scores were impaired short-term memory (1.63), increased effort to remember things (1.41), forgetfulness (1.41), and forgetting names of people (1.41). The symptomatic themes with the highest population impact score (0–4) as reported by caregivers were memory problems (3.05), problems thinking (2.74), and impaired social interactions (2.49). The individual symptoms with the highest population impact score were difficulty managing bills (3.05), forgetfulness (2.98), and impaired short-term memory (2.95). The patient-reported and caregiver-reported population impact scores of all symptom questions are provided in eTable 2.
Self-Reported Demographic Differences in Symptomatic Theme Prevalence
Demographic subgroup analyses revealed numerous differences in symptomatic theme prevalence among study participants who self-reported their symptomatic burden of disease.
There were many associations in symptomatic theme prevalence based on mRS for neurologic disability. Those who reported their level of ability as moderate, moderately severe, or severe experienced 6 of the 12 symptomatic themes at a higher rate than those who no disability or slight or disability. The symptomatic themes with the greatest differences in prevalence between these groups were inability to do activities (p < 0.0001), problems thinking (p = 0.002), decreased satisfaction in social situations (p < 0.0001), pain (p = 0.0006), emotional issues (p = 0.001), and communication difficulties (p < 0.0001).
Individuals above the mean age of 69.1 years reported experiencing pain at a higher rate than those below the mean age (p < 0.001). Those individuals who use assistive devices for mobility reported experiencing greater limitations with mobility and walking than those who walk independently (p = 0.002).
Patient-reported prevalence of symptomatic themes by demographic subgroups and corresponding p-values are provided in Table 2. Subgroup comparisons that did not yield any statistically significant differences were sex, education, marital status, diagnosis, living situation, number of APOE4 copies, home health aide, and medication: anti-anxiety. Subgroup comparisons with p-values <0.05 are not included in Table 2.
Table 2.
Patient-Reported Symptomatic Theme Prevalence
| Change in employment due to disease | Experiences seizures | Genetic test positive for variant associated with AD | Duration of thinking problems Mean = 5.9 y |
|||||||||
| Yes | No | p Value | Yes | No | p Value | Yes | No | p Value | Above the mean | Below the mean | p Value | |
| Limitations with mobility and walking | 42.9 | 44.4 | 1.000 | 85.7 | 39.0 | 0.040 | 46.2 | 40.7 | 0.643 | 45.8 | 41.8 | 0.815 |
| Impaired coordination | 81.0 | 52.8 | 0.024 | 100.0 | 56.8 | 0.040 | 48.0 | 61.7 | 0.336 | 73.9 | 56.3 | 0.152 |
| Inability to do activities | 76.2 | 45.8 | 0.024 | 100.0 | 49.5 | 0.014 | 64.0 | 48.3 | 0.236 | 65.2 | 50.0 | 0.240 |
| Problems thinking | 100.0 | 87.5 | 0.201 | 100.0 | 89.5 | 1.000 | 88.0 | 95.0 | 0.353 | 95.7 | 88.8 | 0.451 |
| Fatigue | 85.7 | 69.4 | 0.171 | 100.0 | 71.6 | 0.185 | 56.0 | 83.3 | 0.012 | 73.9 | 73.8 | 1.000 |
| Memory problems | 100.0 | 98.6 | 1.000 | 100.0 | 99.0 | 1.000 | 100.0 | 98.3 | 1.000 | 100.0 | 98.8 | 1.000 |
| Decreased satisfaction in social situations | 81.0 | 62.9 | 0.185 | 71.4 | 64.5 | 1.000 | 70.8 | 64.4 | 0.619 | 60.9 | 66.7 | 0.625 |
| Impaired sleep or daytime sleepiness | 71.4 | 73.2 | 1.000 | 100.0 | 71.3 | 0.185 | 70.8 | 76.7 | 0.587 | 69.6 | 74.7 | 0.603 |
| Pain | 57.1 | 47.2 | 0.466 | 100.0 | 46.3 | 0.013 | 48.0 | 46.7 | 1.000 | 78.3 | 42.5 | 0.004 |
| Emotional issues | 75.0 | 68.1 | 0.784 | 66.7 | 67.4 | 1.000 | 60.0 | 72.9 | 0.304 | 59.1 | 70.0 | 0.441 |
| Problems with vision/hearing/taste/smell | 71.4 | 69.0 | 1.000 | 100.0 | 66.3 | 0.173 | 79.2 | 66.7 | 0.302 | 56.5 | 72.2 | 0.202 |
| Communication difficulties | 95.2 | 78.9 | 0.107 | 100.0 | 78.7 | 0.340 | 83.3 | 81.7 | 1.000 | 82.6 | 79.8 | 1.000 |
| Full sample | Age mean = 69.1 y |
Mobility status | mRS for neurologic disability | |||||||
| n = 104 | Above the mean | Below the mean | p Value | Walks independently | Uses assistive devices | p Value | No disability to slight disability | Moderate to severe disability | p Value | |
| Limitations with mobility and walking | 42.7 | 53.9 | 29.8 | 0.025 | 39.0 | 100.0 | 0.002a | 30.4 | 56.5 | 0.009 |
| Impaired coordination | 60.2 | 58.8 | 60.4 | 1.000 | 59.0 | 85.7 | 0.241 | 48.2 | 73.9 | 0.009 |
| Inability to do activities | 53.4 | 58.8 | 45.8 | 0.230 | 51.6 | 85.7 | 0.120 | 25.0 | 87.0 | <0.0001a |
| Problems thinking | 90.3 | 88.2 | 91.7 | 0.742 | 89.5 | 100.0 | 1.000 | 82.1 | 100.0 | 0.002a |
| Fatigue | 73.8 | 68.6 | 77.1 | 0.375 | 71.6 | 100.0 | 0.185 | 62.5 | 87.0 | 0.007 |
| Memory problems | 99.0 | 98.0 | 100.0 | 1.000 | 99.0 | 100.0 | 1.000 | 100.0 | 97.8 | 0.451 |
| Decreased satisfaction in social situations | 65.3 | 67.4 | 64.6 | 0.832 | 63.4 | 100.0 | 0.092 | 47.3 | 86.7 | <0.0001a |
| Impaired sleep or daytime sleepiness | 73.5 | 72.0 | 72.9 | 1.000 | 71.3 | 100.0 | 0.185 | 63.6 | 84.8 | 0.024 |
| Pain | 50.5 | 68.6 | 33.3 | <0.001a | 48.4 | 85.7 | 0.113 | 33.9 | 69.6 | 0.0006a |
| Emotional issues | 67.6 | 66.7 | 68.1 | 1.000 | 67.0 | 85.7 | 0.427 | 53.6 | 84.4 | 0.001a |
| Problems with vision/hearing/taste/smell | 68.6 | 76.0 | 58.3 | 0.085 | 67.0 | 85.7 | 0.427 | 67.3 | 69.6 | 0.833 |
| Communication difficulties | 80.4 | 80.0 | 79.2 | 1.000 | 78.7 | 100.0 | 0.340 | 63.5 | 100.0 | <0.0001a |
Statistically significant p values after Benjamini-Hochberg correction.
Caregiver-Reported Demographic Differences in Symptomatic Theme Prevalence
The disease-specific patient characteristics with the greatest associations with symptomatic theme prevalence as reported by caregivers were ambulatory status, mRS for neurologic disability, and duration of thinking problems. Caregivers who reported that the individual they care for uses an ambulatory device reported that these individuals experience 6 symptomatic themes at a higher rate than individuals who walk independently. Individuals who use assistive devices experience a higher disease burden in limitations with mobility and walking (p < 0.0001), impaired coordination (p < 0.0001), inability to do activities (p < 0.0001), fatigue (p < 0.0001), impaired sleep or daytime sleepiness (p < 0.0001), and pain (p < 0.0001).
Individuals rated higher on the mRS scale for neurologic disability were reported by their caregivers to experience 6 symptomatic themes at a higher rate than those with a lower mRS score. These 6 symptomatic themes include limitations with mobility and walking (p = 0.001), impaired coordination (p < 0.0001), inability to do activities (p < 0.0001), fatigue (p < 0.0001), impaired social interactions (p < 0.0001), and impaired sleep or daytime sleepiness (p < 0.0001). Individuals who were reported to have a longer duration of thinking problems (above the mean) experienced 5 symptomatic themes at a higher rate than those with a shorter duration of thinking problems (below the mean): limitations with mobility and walking (p = 0.015), impaired coordination (p = 0.001), inability to do activities (p < 0.001), fatigue (p = 0.006), impaired sleep or daytime sleepiness (p < 0.001), and communication difficulties (p = 0.002).
Individuals who have a home health aide were reported to experience limitations with mobility and walking (p < 0.0001), impaired coordination (p = 0.0001), and inability to do activities (p = 0.002) at a higher rate than those who do not have a home health aide.
Patient diagnosis of AD revealed an association with a higher prevalence for 5 symptomatic themes: impaired coordination (p = 0.004), inability to do activities (p < 0.0001), fatigue (p = 0.003), impaired social interactions (p < 0.0001), and communication difficulties (p = 0.008).
Subgroup analysis by relationship status indicated 65.6% of those who were married or in a registered partnership experienced limitations with mobility and walking, compared with 87.2% (p < 0.0001) of those who were not married or in a partnership. Similarly, those individuals living in an independent living facility, assisted living facility, skilled nursing facility, or other experienced greater limitations with mobility and walking than whose who reside in the community (p = 0.008).
Caregivers who indicated that they were the spouse or partner of the affected individual reported that the person for whom they cared experienced 7 symptomatic themes at a statistically significant lower rate than caregivers who were sons daughters, home health aides, or selected their relationship as “other.” Caregivers who were partners or spouses reported a lower prevalence of limitations with mobility and walking (p < 0.0001), impaired coordination (p < 0.0001), inability to do activities (p < 0.001), fatigue (p = 0.001), impaired social interactions (p = 0.002), pain (p < 0.0001), and emotional issues (p = 0.002).
Caregivers who indicated that the individual for whom they care had a genetic test that was positive for a mutation associated with AD-reported higher levels of pain (p = 0.010) than those who did not have a positive genetic test. Individuals who take anti-anxiety medicine were reported to experience emotional issues at a higher rate than those who do not (p = 0.011). Caregivers providing care for individuals with an educational status below a college degree indicated a higher prevalence of inability to do activities (p = 0.011) and emotional issues (0.005). There were no statistically significant findings associated with patient sex, number of APOE4 copies, caregiver sex, patient employment change due to disease, and seizures. Full details regarding caregiver-reported symptomatic theme prevalence and corresponding p values are provided in Table 3.
Table 3.
Caregiver-Reported Symptomatic Theme Prevalence
| Full sample | Patient age mean = 65.1 y |
Mobility status | mRS for neurologic disability | |||||||
| n = 329 | Above the mean | Below the mean | p Value | Walks independently | Uses assistive devices | p Value | No disability to slight disability | Moderate to severe disability | p Value | |
| Limitations with mobility and walking | 74.5 | 72.5 | 76.4 | 0.447 | 56.1 | 99.3 | <0.0001a | 33.3 | 74.4 | 0.001a |
| Impaired coordination | 78.4 | 74.5 | 82.3 | 0.105 | 66.7 | 94.0 | <0.0001a | 33.3 | 78.7 | <0.0001a |
| Inability to do activities | 89.7 | 87.5 | 92.1 | 0.120 | 82.5 | 99.3 | <0.0001a | 29.4 | 92.1 | <0.0001a |
| Problems thinking | 99.7 | 99.4 | 100.0 | 0.494 | 99.5 | 100.0 | 1.000 | 94.4 | 100.0 | 0.061 |
| Fatigue | 90.5 | 86.8 | 93.9 | 0.037 | 85.1 | 98.5 | <0.0001a | 55.6 | 92.4 | <0.0001a |
| Memory problems | 99.4 | 98.8 | 100.0 | 0.245 | 98.9 | 100.0 | 0.514 | 94.4 | 99.6 | 0.119 |
| Impaired social interactions | 95.4 | 92.5 | 98.2 | 0.017 | 93.7 | 97.7 | 0.110 | 47.1 | 97.8 | <0.0001a |
| Impaired sleep or daytime sleepiness | 86.9 | 82.4 | 91.5 | 0.020 | 80.2 | 96.2 | <0.0001a | 41.2 | 88.4 | <0.0001a |
| Pain | 59.3 | 48.5 | 70.4 | <0.0001a | 46.6 | 77.1 | <0.0001a | 33.3 | 57.9 | 0.051 |
| Emotional issues | 87.2 | 81.3 | 92.7 | 0.003a | 84.1 | 91.7 | 0.061 | 70.6 | 87.4 | 0.064 |
| Communication difficulties | 93.6 | 91.9 | 95.1 | 0.265 | 91.5 | 96.2 | 0.110 | 82.4 | 93.5 | 0.111 |
| Relationship status of patient | Diagnosis | Years since first had problems thinking mean = 7.3 y |
Home health aide | |||||||||
| Married/registered partnership | Single/widowed/divorced/separated/other | p Value | AD | MCI | p Value | Below the mean | Above the mean | p Value | Yes | No | p Value | |
| Limitations with mobility and walking | 65.5 | 87.2 | <0.0001a | 73.4 | 57.5 | 0.049 | 70.4 | 83.5 | 0.015 | 92.2 | 69.4 | <0.0001a |
| Impaired coordination | 71.7 | 88.7 | <0.001a | 80.2 | 59.6 | 0.004a | 70.6 | 87.8 | 0.001a | 93.5 | 73.8 | 0.0001a |
| Inability to do activities | 85.9 | 94.7 | 0.010a | 93.3 | 63.0 | <0.0001a | 83.7 | 97.4 | <0.001a | 98.7 | 87.1 | 0.002a |
| Problems thinking | 99.5 | 100.0 | 1.000 | 99.5 | 100.0 | 1.000 | 100.0 | 99.1 | 0.418 | 100.0 | 99.6 | 1.000 |
| Fatigue | 87.3 | 94.7 | 0.034 | 92.7 | 76.6 | 0.003a | 86.2 | 96.5 | 0.006a | 94.7 | 89.5 | 0.257 |
| Memory problems | 99.5 | 99.3 | 1.000 | 99.5 | 100.0 | 1.000 | 100.0 | 99.1 | 0.416 | 100.0 | 99.2 | 1.000 |
| Impaired social interactions | 93.2 | 98.5 | 0.030 | 97.9 | 80.0 | <0.0001a | 93.6 | 98.3 | 0.078 | 100.0 | 93.9 | 0.026 |
| Impaired sleep or daytime sleepiness | 85.2 | 89.5 | 0.314 | 89.1 | 73.9 | 0.015 | 79.4 | 94.7 | <0.001a | 92.2 | 85.4 | 0.173 |
| Pain | 50.0 | 72.7 | <0.0001a | 61.1 | 44.7 | 0.048 | 56.0 | 64.6 | 0.169 | 64.5 | 57.7 | 0.350 |
| Emotional issues | 84.2 | 91.0 | 0.093 | 86.9 | 83.0 | 0.484 | 84.4 | 88.5 | 0.378 | 92.1 | 85.5 | 0.172 |
| Communication difficulties | 91.6 | 96.2 | 0.111 | 95.3 | 83.0 | 0.008a | 90.0 | 99.1 | 0.002a | 97.4 | 92.3 | 0.182 |
| Caregiver relationship to the patient | Caregiver relationship to the patient | Patient living situation | |||||||
| Spouse/partner | Son/daughter | p Value | Spouse/partner | Son/daughter/home health aide/other relative/other | p Value | Reside in community | Independent living facility, assisted living facility, skilled nursing facility, other | p Value | |
| Limitations with mobility and walking | 60.3 | 87.8 | <0.0001a | 60.3 | 86.5 | <0.0001a | 70.8 | 85.4 | 0.008a |
| Impaired coordination | 65.8 | 89.7 | <0.0001a | 65.8 | 89.3 | <0.0001a | 76.6 | 85.2 | 0.118 |
| Inability to do activities | 82.8 | 95.9 | <0.001a | 82.8 | 95.5 | <0.001a | 87.2 | 96.3 | 0.021 |
| Problems thinking | 99.3 | 100.0 | 1.000 | 99.3 | 100.0 | 0.461 | 99.6 | 100.0 | 1.000 |
| Fatigue | 84.8 | 95.2 | 0.003a | 84.8 | 95.5 | 0.001a | 88.8 | 95.1 | 0.127 |
| Memory problems | 99.3 | 100.0 | 1.000 | 99.3 | 99.4 | 1.000 | 99.2 | 100.0 | 1.000 |
| Impaired social interactions | 91.4 | 99.3 | 0.002a | 91.4 | 98.9 | 0.002a | 94.2 | 98.8 | 0.128 |
| Impaired sleep or daytime sleepiness | 82.0 | 90.4 | 0.043 | 82.0 | 91.0 | 0.021 | 84.2 | 93.9 | 0.025 |
| Pain | 45.0 | 71.0 | <0.0001a | 45.0 | 71.6 | <0.0001a | 56.4 | 68.8 | 0.066 |
| Emotional issues | 80.8 | 91.8 | 0.007a | 80.8 | 92.7 | 0.002a | 86.8 | 87.8 | 1.000 |
| Communication difficulties | 90.0 | 96.6 | 0.035 | 90.0 | 96.6 | 0.022 | 91.8 | 99.8 | 0.034 |
| Genetic test positive for variant associated with AD | Anti-anxiety medication | Education status | |||||||
| Yes | No | p Value | Taking anti-anxiety medication | Not taking anti-anxiety medication | p Value | College, Master's or doctorate | Below a college degree | p Value | |
| Limitations with mobility and walking | 53.3 | 74.3 | 0.029 | 73.9 | 74.4 | 1.000 | 71.2 | 78.3 | 0.160 |
| Impaired coordination | 63.3 | 77.9 | 0.109 | 79.7 | 71.8 | 0.295 | 76.0 | 81.5 | 0.277 |
| Inability to do activities | 75.9 | 90.9 | 0.022 | 94.3 | 87.9 | 0.204 | 85.3 | 94.1 | 0.011a |
| Problems thinking | 96.7 | 100.0 | 0.106 | 100.0 | 99.2 | 1.000 | 100.0 | 99.3 | 0.471 |
| Fatigue | 82.8 | 90.5 | 0.198 | 94.3 | 86.2 | 0.094 | 88.8 | 92.1 | 0.349 |
| Memory problems | 96.7 | 100.0 | 0.106 | 100.0 | 99.1 | 1.000 | 99.4 | 99.3 | 1.000 |
| Impaired social interactions | 93.3 | 95.2 | 0.651 | 98.5 | 94.8 | 0.263 | 93.5 | 98.0 | 0.059 |
| Impaired sleep or daytime sleepiness | 86.2 | 84.9 | 1.000 | 88.6 | 83.6 | 0.397 | 84.7 | 88.7 | 0.328 |
| Pain | 34.5 | 60.3 | 0.010a | 61.0 | 52.1 | 0.286 | 54.1 | 64.7 | 0.068 |
| Emotional issues | 85.7 | 85.8 | 1.000 | 97.1 | 80.2 | 0.001a | 81.8 | 92.7 | 0.005a |
| Communication difficulties | 89.7 | 94.5 | 0.398 | 95.7 | 92.2 | 0.540 | 91.8 | 96.0 | 0.165 |
Statistically significant p values after Benjamini-Hochberg.
Discussion
This research builds on existing literature that has explored and characterized the lived experiences of individuals with AD, MCI, and dementia through the perspectives of patients and caregivers.24-27 This study used a unique, patient-centric approach to define the complex disease burden faced by individuals with these conditions. This data set highlights the patient-reported and caregiver-reported symptoms and symptomatic themes that are most frequent and burdensome to this population, and identifies subpopulation characteristics that are associated with the prevalence of select symptomatic themes.
It is important that this research shows that individuals with cognitive symptoms have the potential to provide direct insight into their disease burden using a survey questionnaire. Although the patient-reported sample primarily consisted of individuals with MCI (72.12%), participants with AD (15.38%), and 7.68% of those with dementia participated in this research. This finding is similar to what we have observed in other disease populations experiencing cognitive symptoms (e.g., Huntington disease and myotonic dystrophy) who were also able to provide insight into their own health and disease state.8,12 Alternatively, the caregiver-reported sample was mostly comprised of individuals with AD (58.36%) followed by 15.51% with dementia and 14.29% with MCI, providing insight to those with more severe disease states. Owing to limitations in the number of individuals with dementia for both the patient-reported and caregiver-reported surveys, we were not able to conduct subgroup analyses of individuals with dementia vs AD and MCI.
Our caregiver-reported study indicated that individuals with AD were reported to have a statistically significant higher prevalence of 5 symptomatic themes than those with MCI. Furthermore, problems thinking and memory problems were not part of those symptomatic themes with a statistically significant difference. This result may seem contradictory to the clinical phenotype of MCI as a condition with milder memory and thinking problem symptoms than AD or dementia. This result is likely secondary to the extremely high rates of thinking and memory problems in both of these populations. It is important to note that AD and MCI are different clinical entities with different phenotypes. It is worthwhile to compare and highlight the differences and similarities of these conditions as patients with these conditions may respond differently to future therapeutic interventions.
Despite a historical emphasis on memory impairment and cognitive functioning, our study revealed that decreased satisfaction in social situations and fatigue were of highest importance to patients as indicated by patient-reported average impact scores. Caregivers also reported that impaired social interactions were highly impactful to the individuals for whom they care; however, caregivers rated memory problems and problems thinking as the most impactful symptomatic themes. This is likely a function of the fact that caregivers in the cross-sectional study were reporting on individuals with a greater degree of memory and cognitive impairment than the patient-reported sample.
There were several patient-reported and caregiver-reported markers of disease state that were statistically associated with symptomatic theme prevalence. Specifically, we found that mobility status, mRS, and the number of years because the affected individual first experienced problems thinking all had significant associations with symptomatic themes across multiple domains of health. Previous research has also demonstrated that ambulatory impairment is correlated with increased dementia severity.28
We found that an inability to do activities, decreased satisfaction in social interactions, and communication difficulties were highly associated with one's mRS for neurologic disability status. We also found that one's ability to ambulate was not only strongly associated with their need for a home health aide, but also their living situation and their marital status.
Notably, we found that the relationship of the caregiver to the patient had a significant impact on the prevalence of select symptomatic themes. Caregivers who were sons or daughters, home health aides, other relatives, or “other” reported multiple symptomatic themes at a higher rate than those who were spouses or partners. Previous research has explored the differences in perspectives of spouse vs child caregivers of individuals with dementia and reported that child caregivers did not see the affected individual as often as spouses, self-reported having a lower quality-of-life, and experienced greater social support than did spouse caregivers.29 These previous findings provide a potential framework for understanding differences in symptomatic themes based on the role of the reporter observed in our data set. Also in agreement with our findings, another quality-of-life study in Alzheimer disease found that spouse caregivers had a more positive perspective on the affected individual's quality-of-life than child caregivers.30 These data provide insight into the unique perspectives of caregivers for those with AD, MCI, and dementia and how the type of relationship of the caregiver affects the view of an affected individual's disease and quality-of-life.
Similarly, a comparison of caregiver-reported to patient-reported prevalence of symptoms as given in Table 2 reveals that caregivers consistently reported a higher symptom burden than patients. This finding could be a result of patients having less awareness of their symptoms. However, it is more likely that this is an indication of the diagnostic distribution within the patient and caregiver samples because the patient sample consisted primarily of individuals with MCI and the caregiver sample mainly of those with AD. The higher disease severity of the caregiver-reported population as indicated by diagnosis would account for higher symptom prevalence.
This research importantly highlights the areas of patient-reported and caregiver-reported disease burden that differ between MCI and AD. Key differences in caregiver-reported symptomatic theme prevalence between AD and MCI were a higher rate of impaired coordination, inability to do activities, fatigue, impaired social interactions, and impaired communication in AD. Owing to limitations in the number of participants with dementia in both the patient-reported and caregiver-reported samples, we were not able to conduct analyses by diagnosis among individuals with dementia, AD, and MCI.
Although nearly 2/3 of the population of Americans with AD are women, our study did not reveal any statistically significant differences in symptomatic theme prevalence by sex.
We acknowledge the limitations to this research. Owing to the online format, we suspect that those with limited access to the internet were underrepresented in our sample. We also suspect that individuals with more severe disease were underrepresented in our patient-reported sample due to physical and/or cognitive limitations interfering with one's ability to participate. It is important that there was limited participation by minority groups throughout this research. It has been previously reported that Black Americans are disproportionally affected by AD and other dementias than individuals of other races.31-33 Our study demographics further underscore the longstanding barriers to minority participation in AD, MCI, and dementia research. These results emphasize the need to address barriers to research participation and develop new ways of effectively reaching underrepresented communities.34
Our research adds to existing knowledge of the multifaceted disease burden faced by individuals living with AD, MCI, or dementia using the direct perspectives of those living with these diseases and their caregivers. Our findings have implications for the identification of areas of disease burden that are uniquely important to MCI, AL, and dementia. We have extensively detailed the prevalence of all symptoms faced by individuals with AD, MCI, and dementia that may serve as future targets for therapeutic intervention and serve as valuable metrics for existing Quality-of-Life measures and disease-specific outcome measure development. Future instruments should strive to comprehensively address and measure the symptomatic themes most important to patients to ensure comprehensive assessment of disease burden during clinical trials.
Acknowledgment
This research was conducted in collaboration with the Banner Health Institute Alzheimer's Prevention Registry.
Appendix. Authors
|
Name |
Location |
Contribution |
|
Jamison Seabury, BS |
University of Rochester School of Medicine and Dentistry; Center for Health and Technology (CHeT), University of Rochester |
Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data |
|
Jennifer Weinstein, MS |
Center for Health and Technology (CHeT), University of Rochester |
Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data |
|
Anika Varma |
University of Rochester School of Medicine and Dentistry; Center for Health and Technology (CHeT), University of Rochester |
Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data |
|
Spencer James Rosero |
Center for Health and Technology (CHeT), University of Rochester; University of Utah Spencer Fox Eccles School of Medicine |
Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data |
|
Charlotte Engebrecht, BS |
Center for Health and Technology (CHeT), University of Rochester |
Drafting/revision of the manuscript for content, including medical writing for content |
|
Abigail Arky, DO |
Center for Health and Technology (CHeT), University of Rochester; Des Moines University College of Osteopathic Medicine |
Major role in the acquisition of data |
|
Christine Zizzi, MPA |
Center for Health and Technology (CHeT), University of Rochester |
Major role in the acquisition of data |
|
Nuran Dilek, MS |
Department of Biostatistics and Neurology, University of Rochester |
Analysis or interpretation of data |
|
Abigail Mathewson, RN |
Alzheimer's Disease Care, Research and Education Program (AD-CARE), University of Rochester |
Major role in the acquisition of data |
|
Susan Salem-Spencer, RN, MSN, CCRC |
Alzheimer's Disease Care, Research and Education Program (AD-CARE), University of Rochester |
Major role in the acquisition of data |
|
Elizabeth J. Santos, MD, MPH |
Alzheimer's Disease Care, Research and Education Program (AD-CARE), University of Rochester |
Major role in the acquisition of data |
|
Chad Rydel Heatwole, BS, MD |
Center for Health and Technology (CHeT); Department of Neurology, University of Rochester |
Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data |
Study Funding
The authors report no targeted funding.
Disclosure
C. Heatwole receives royalties for the use of multiple disease-specific instruments. He has provided consultation to Biogen Idec, Ionis Pharmaceuticals, aTyr Pharma, AMO Pharma, Acceleron Pharma, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron Pharmaceuticals, Astellas Pharmaceuticals, AveXis, Recursion Pharmaceuticals, IRIS Medicine, Inc., Takeda Pharmaceutical Company, Scholar Rock, Avidity Biosciences, Novartis Pharmaceuticals Corporation, SwanBio Therapeutics, Neurocrine Biosciences, and the Marigold Foundation. He receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, Swan Bio Therapeutics, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the Friedreich's Ataxia Research Alliance, Cure Spinal Muscular Atrophy, and the Amyotrophic Lateral Sclerosis Association. He is the director of the University of Rochester Center for Health + Technology. C. Zizzi has provided consultation to Recursion Pharmaceuticals. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
References
- 1.Alzheimer’s Association. 2024 Alzheimer's disease facts and figures. Alzheimers Dement. 2024;20(5):3708-3821. doi: 10.1002/alz.13809 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011;10(9):819-828. doi: 10.1016/S1474-4422(11)70072-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.López OL, DeKosky ST. Clinical symptoms in alzheimer's disease. Handbook Clin Neurol. 2008;89:207-216. doi: 10.1016/S0072-9752(07)01219-5 [DOI] [PubMed] [Google Scholar]
- 4.Mendez MF, Martin RJ, Smyth KA, Whitehouse PJ. Psychiatric symptoms associated with Alzheimer's disease. J Neuropsychiatry Clin Neurosci. 1990;2(1):28-33. doi: 10.1176/jnp.2.1.28 [DOI] [PubMed] [Google Scholar]
- 5.Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet. 2006;367(9518):1262-1270. doi: 10.1016/S0140-6736(06)68542-5 [DOI] [PubMed] [Google Scholar]
- 6.Logsdon R, Gibbons L, McCurry S, Teri L. Quality of life in Alzheimer's disease: patient and caregiver reports. J Ment Health Aging. 1999;5(1):21-32. [Google Scholar]
- 7.Walters S. Assessing quality of life in clinical trials: 2nd edition analysis and interpretation. Peter Fayers and Ron Hays (eds). Oxford University Press, 2005, pp. 467, ISBN: 0-19-852769-1. Int J Epidemiol. 2005;34(6):1447-1448. doi: 10.1093/ije/dyi221 [DOI] [Google Scholar]
- 8.Heatwole C, Bode R, Johnson N, et al. Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1) [published correction appears in Neurology. 2012 Sep 25;79(13):1411]. Neurology. 2012;79(4):348-357. doi: 10.1212/WNL.0b013e318260cbe6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Heatwole C, Johnson N, Bode R, et al. Patient-reported impact of symptoms in myotonic dystrophy type 2 (PRISM-2). Neurology. 2015;85(24):2136-2146. doi: 10.1212/WNL.0000000000002225 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Johnson NE, Heatwole CR, Dilek N, et al. Quality-of-life in Charcot-Marie-Tooth disease: the patient's perspective. Neuromuscul Disord. 2014;24(11):1018-1023. doi: 10.1016/j.nmd.2014.06.433 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Mongiovi P, Dilek N, Garland C, et al. Patient reported impact of symptoms in spinal muscular atrophy (PRISM-SMA). Neurology. 2018;91(13):e1206-e1214. doi: 10.1212/WNL.0000000000006241 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Glidden AM, Luebbe EA, Elson MJ, et al. Patient-reported impact of symptoms in Huntington disease: PRISM-HD. Neurology. 2020;94(19):e2045-e2053. doi: 10.1212/WNL.0000000000008906 [DOI] [PubMed] [Google Scholar]
- 13.Hamel J, Johnson N, Tawil R, et al. Patient-reported symptoms in facioscapulohumeral muscular dystrophy (PRISM-FSHD). Neurology. 2019;93(12):e1180-e1192. doi: 10.1212/WNL.0000000000008123 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Johnson NE, Quinn C, Eastwood E, Tawil R, Heatwole CR. Patient-identified disease burden in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2012;46(6):951-953. doi: 10.1002/mus.23529 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Zizzi C, Seabury J, Rosero S, et al. Patient reported impact of symptoms in amyotrophic lateral sclerosis (PRISM-ALS): a national, cross-sectional study. eClinicalMedicine. 2023;55:101768. doi: 10.1016/j.eclinm.2022.101768 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Seabury J, Alexandrou D, Dilek N, et al. Patient-reported impact of symptoms in Friedreich ataxia. Neurology. 2023;100(8):e808–e821. doi: 10.1212/WNL.0000000000201598 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Varma A, Weinstein J, Seabury J, et al. Patient-reported impact of symptoms in Crohn's disease. Am J Gastroenterol. 2022;117(12):2033-2045. doi: 10.14309/ajg.0000000000001954 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Rosero S, Weinstein J, Seabury J, et al. Disease burden in children with spinal muscular atrophy: results from a large cross-sectional study. J Child Neurol. 2023;38(1-2):52-63. doi: 10.1177/08830738221135918 [DOI] [PubMed] [Google Scholar]
- 19.Varma A, Weinstein J, Seabury J, et al. Patient-reported impact of symptoms in lung cancer (PRISM-LC). Transl Lung Cancer Res. 2023;12(7):1391-1413. doi: 10.21037/tlcr-22-831 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Varma A, Weinstein J, Seabury J, et al. Patient-reported impact of symptoms in Adrenoleukodystrophy (PRISM-ALD). Orphanet Journal Rare Diseases 2024;19(1):127. doi: 10.1186/s13023-024-03129-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Weinstein J, Rosero S, Seabury J, et al. Patient Reported Impact of Symptoms in Fibromyalgia (PRISM-FM). Accepted to Journal of Rheumatology; 2024. [DOI] [PubMed] [Google Scholar]
- 22.Rosero S, Weinstein J, Seabury J, et al. Patient- and caregiver-reported impact of symptoms in Duchenne muscular dystrophy. Muscle Nerve. 2024;70(1):120-129. doi: 10.1002/mus.28102 [DOI] [PubMed] [Google Scholar]
- 23.Broderick JP, Adeoye O, Elm J. Evolution of the modified rankin scale and its use in future stroke trials. Stroke. 2017;48(7):2007-2012. doi: 10.1161/STROKEAHA.117.017866 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Górska S, Forsyth K, Maciver D. Living with dementia: a meta-synthesis of qualitative research on the lived experience. Gerontologist. 2018;58(3):e180-e196. doi: 10.1093/geront/gnw195 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Eriksen S, Engedal K, Grov EK. Lifeworld perspectives of people with dementia: a meta-aggregation of qualitative studies. BMC Geriatrics. 2022;22(1):970. doi: 10.1186/s12877-022-03660-w [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Shin IS, Carter M, Masterman D, Fairbanks L, Cummings JL. Neuropsychiatric symptoms and quality of life in Alzheimer disease. The Am Journal Geriatric Psychiatry. 2005;13(6):469-474. doi: 10.1176/appi.ajgp.13.6.469 [DOI] [PubMed] [Google Scholar]
- 27.Watson J, Saunders S, Muniz Terrera G, et al. What matters to people with memory problems, healthy volunteers and health and social care professionals in the context of developing treatment to prevent Alzheimer's dementia? A qualitative study. Health Expectations. 2019;22(3):504-517. doi: 10.1111/hex.12876 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Lee HH, Hong CT, Wu D, et al. Association between ambulatory status and functional disability in elderly people with dementia. Int J Environ Res Public Health. 2019;16(12):2168. doi: 10.3390/ijerph16122168. 2017;48(7):2007-2012. doi:10.1161/STROKEAHA.117.017866 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Rigby T, Ashwill RT, Johnson DK, Galvin JE. Differences in the experience of caregiving between spouse and adult child caregivers in dementia with Lewy bodies. Innov Aging. 2019;3(3):igz027. doi: 10.1093/geroni/igz027.BA. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Conde-Sala JL, Garre-Olmo J, Turró-Garriga O, Vilalta-Franch J, López-Pousa S. Quality of life of patients with Alzheimer's disease: differential perceptions between spouse and adult child caregivers. Demen Geriatr Cogn Disord. 2010b;29(2):97-108. doi: 10.1159/000272423 [DOI] [PubMed] [Google Scholar]
- 31.Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimers Dement. 2016;12(3):216-224. doi: 10.1016/j.jalz.2015.12.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Tang MX, Cross P, Andrews H, et al. Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology. 2001;56(1):49-56. doi: 10.1212/wnl.56.1.49 [DOI] [PubMed] [Google Scholar]
- 33.Rajan KB, Weuve J, Barnes LL, Wilson RS, Evans DA. Prevalence and incidence of clinically diagnosed Alzheimer's disease dementia from 1994 to 2012 in a population study. Alzheimers Dement. 2019;15(1):1-7. doi: 10.1016/j.jalz.2018.07.216 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Parker LJ, Gaugler JE, Gitlin LN. Use of critical race theory to inform the recruitment of Black/African American Alzheimer's Disease Caregivers into Community-Based Research. The Gerontologist 2022;62(5):742-750. doi: 10.1093/geront/gnac001 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Additional anonymized data not included in the article or supplemental files can be obtained through request to the corresponding author.