Abstract
Aim
To conduct a prospective analysis of the neuropsychiatric symptoms(NPS) across the three categories of primary progressive aphasia(PPA) and apraxia of speech(PPAOS), to compare the prevalence and nature of the symptoms, and look at which symptoms could be helpful to better differentiate these PPA and PPAOS categories.
Methods
106 consecutive patients with a diagnosis of semantic variant{svPPA}(13), logopenic variant{lvPPA}(37), agrammatic variant{agPPA}(15) or PPAOS(41), were included in this prospective study. The NPS were measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q).
Results
There were 65 patients with PPA and 41 with PPAOS diagnosis. The most distinguishing features between the two groups were anxiety, apathy, aberrant motor behavior and appetite, while among the subtypes of PPA were disinhibition and appetite changes. PPA and PPAOS patients initially exhibited depression but with increase in disease duration, the PPAOS patients showed apathy (55.5%) while the PPA patients showed disinhibition (28.6%) and aberrant motor behavior (14.3%).
Conclusion
Mood symptoms like anxiety and appetite changes are more likely to be present in initial stages of PPA whereas behavioral symptoms like aberrant motor behavior and apathy are likely to occur in PPAOS. The NPS seems to evolve with the progression of the disease in both PPA and PPAOS.
Keywords: neuropsychiatric symptoms, primary progressive aphasia, primary progressive apraxia of speech
Introduction
Primary progressive aphasia (PPA) is a group of neurodegenerative disorders which present with language impairment as the most characteristic feature.[1] The diagnosis of PPA requires that an insidiously progressive language impairment be the primary cognitive deficit for approximately 2 years after the symptom onset with no or minimal change in other cognitive functions including memory, visuospatial skills and executive abilities.[2] However, as the disease progresses other cognitive domains may become impaired leading to PPA-plus, although the language impairment remains the most prominent anomaly.[3] A new classification was proposed in 2011 segregating the PPA patients into three categories based on their type of speech impairment.[4] The first category is known as semantic variant (svPPA) and is characterized by anomia and impaired single word comprehension. Second is logopenic variant (lvPPA) characterized by impaired single word retrieval and impaired repetition of phrases. The third is agrammatic variant (agPPA), which includes patients with grammatical errors in written and verbal language. More recently another category of patients with neurodegenerative speech disorders have been identified known as primary progressive apraxia of speech (PPAOS). These patients present with a motor speech neurodegerative disorder with speech impairment being the only sign or symptom.[5,6]
Since PPA and PPAOS are primarily neurodegerative speech disorders, there has been a lot of research looking into the neuropathology and clinical features. However, little has been reported about the neuropsychiatric aspects. These aspects may be helpful as clinical markers for different stages and may help in categorizing patients between PPA and PPAOS. There have been some studies looking at the neuropsychiatric symptoms (NPS) of PPA [7–10] but only one analyzed the symptoms according to PPA subtypes [10], and that study used an older PPA classification. Most of the previous studies also had relatively smaller cohorts. There have not been any studies looking into the neuropsychiatric aspects of PPAOS patients.
In this study we conducted a prospective analysis of the NPS across the three categories of PPA and PPAOS, to compare the prevalence and nature of the symptoms and look at the factors that may help us to better differentiate these categories.
Methods
Standard protocols approvals and patient consents
The study was approved by the Mayo Clinic institutional review board and all subjects signed consent forms for enrollment into the study.
Patient selection
All patients who presented to the Mayo Clinic in Rochester, Minnesota between July 2010 and March 2014 with a suspected speech and language disorder, secondary to a neurodegenerative process were recruited prospectively. Subjects with concurrent illnesses that could account for language deficits or meeting criteria for other neurodegenerative syndrome were excluded. Only patients over the age of 18, with an informant to provide independent evaluation of functioning and who spoke English as their primary language were included. All patients underwent detailed speech and language examination, neurological evaluation, neuropsychological testing and neuroimaging analysis over a span of 48–72 hrs.
Clinical diagnostic classification
To be included in the study, patients must have had svPPA, lvPPA, agPPA or PPAOS. Patients with PPA as a primary diagnosis and who were not able to be classified among any of the three categories (svPPA, lvPPA, and agPPA) were not included for this study. Quantitative scores and video recordings of all the crucial aspects of the speech and language assessments were reviewed for all the study participants by 2 speech-language pathologists separately (J.R.D. and E.A.S.) for consensus agreement about the diagnosis.
Study participants who by consensus agreement, demonstrated solely Apraxia of Speech (AOS) without features of aphasia, were classified as primary progressive apraxia of speech (PPAOS), based on the published criteria.[6] Any participant who by mutual agreement among speech pathologists, demonstrated features of progressive aphasia was analyzed for the diagnostic features of each PPA subtype as described below. All participants had disrupted normal activities of daily living (talking on phone, writing a letter) due to speech or language dysfunction. None complained of early deficits in other cognitive domains.
In accordance with the consensus guidelines for the classification of PPA, tasks for evaluation of speech and language functions were qualitatively utilized for the assessment of the presence or absence of each diagnostic feature of individual variant.
Neuropsychiatric Examination
All patients underwent detailed neurological examination by a behavioral and movement disorders specialist (K.A.J.), as well as standardized testing of cognitive, behavioral, functional and motor performance.
The Neuropsychiatric symptoms of all the cases across different categories were measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) [11]. The NPI-Q measures and grades 12 behavioral domains; according to the severity of the symptoms and the distress that is experienced by the caregiver due to those symptoms in the last 30 days. The distress index was not analyzed for this study. The severity of the symptoms was graded as 1–3 with 1 being mild and 3 being severe. The 12 behavioral domains that are measured can be subcategorized as behavioral/compartmental (aberrant motor, disinhibition, apathy/indifference), appetite/eating disorder, mood symptoms (anxiety, euphoria/elation, irritability/lability, depression) and disruptive/psychotic symptoms (delusions, hallucinations, agitation/aggression, nighttime behavior). Adding the total score of the 12 behavioral domains yielded the total NPI score. In our study population, the NPI-Q testing was done by a behavior neurologist (K.A.J.). NPI-Q has been shown to be a reliable and valid scale for testing of NPS. [11,12]
Statistical analysis
Statistical analysis was performed using JMP 9.0.1(SAS Institute Inc., Cary, NC). The analysis was done at the conventional two-tailed alpha level of 0.05. Group differences for categorical variables were assessed with the χ2 test and Fisher’s exact test for small numbers. Differences in the continuous variables were assessed using the Kruskal–Wallis one-way analysis of variance. Mann-Whitney U post hoc testing was performed if Kruskal-Wallis testing was significant. Multivariate regression analysis was used to compare the two groups of PPA and PPAOS, and the Odds Ratio (OR) and 95% Confidence Interval (CI) were computed. Demographics and neuropsychological profiles were summarized as percent and mean ± SD.
Results
We included 106 patients {56(52.8%) males and 50 (47.2%) females} with the mean age of onset of 63.9±8.1 yrs. who fulfilled the above criteria for the diagnosis of either PPA or PPAOS during the study period. The mean age at testing was 66.8±8 yrs. and their Mini-Mental State Exam (MMSE) was 27.3±2.5. After the final segregation, there were 65 patients with PPA and 41 with PPAOS diagnosis. When the PPA patients were further categorized in accordance with the latest guidelines [4], it yielded 15(23.1%) agPPA, 37(56.9%) lvPPA and 13(20.0%) with svPPA diagnosis. The only significant difference between PPA and PPAOS was on MMSE, with patients with PPAOS presenting with a significantly higher mean MMSE. However, MMSE and illness duration were different among the various subtypes of PPA. The breakdown of the demographic variables, education, MMSE, age at onset and testing, according to their final diagnosis is presented in Table 1. The demographics according the subtype of PPA are presented in Table 2.
Table-1.
Demographics according to diagnosis
| PPA | PPAOS | p value | |
|---|---|---|---|
| No of patients | 65(61.3%) | 41(38.7%) | |
| Males | 33(50.7%) | 23(56.1%) | 0.5922 |
| Right handedness* | 57(87.7%) | 35(85.4%) | 0.6091 |
| Age at onset | 62.3±7.4 | 65±8.9 | 0.1092 |
| Illness duration | 3.2±2 | 3.7±1.8 | 0.1856 |
| Age at test | 65.5±7.4 | 68.7±8.7 | 0.0555 |
| MMSE | 26.7±2.5 | 28.3±2.1 | 0.0005 |
| Education | 16±2.7 | 15.3±2.7 | 0.1545 |
Continuous variables presented as mean± standard deviation
One patient was Amphidextrous among the PPAOS cohort.
Table-2.
Demographics according to subtypes of PPA
| agPPA | IvPPA | svPPA | p value | |
|---|---|---|---|---|
| No of patients | 15(14.2%) | 37(34.9%) | 13(12.2%) | |
| Males | 6(40%) | 21(56.8%) | 6(46.2%) | 0.6762 |
| Right handedness | 13(86.6%) | 34(91.9%) | 10(76.9%) | 0.6801 |
| Age at onset | 63.6±8.6 | 62.1±7.3 | 61.7±6.5 | 0.357 |
| Illness duration | 2.3±1.4 | 3.2±1.5 | 4.2±3.4 | 0.014a |
| Age at test | 65.9±8.2 | 65.3±7.6 | 65.8±6.3 | 0.2578 |
| MMSE | 27.3±2.8 | 26±2.3 | 27.8±2.1 | 0.025b |
| Education | 15.5±3.4 | 15.9±2.5 | 17±2.2 | 0.228 |
Significance achieved between svPPA and agPPA
Significance achieved between svPPA and lvPPA
Continuous variables presented as mean± standard deviation
There were no significant differences in the NPS symptoms between the PPA and PPAOS patient groups, when they are compared according to the severity of the NPI score. The frequency of distribution of NPS across PPA and PAOS, according to the NPI breakdown is shown in Table 3 and Figure 1. However, significant differences become more apparent when the two groups were compared according to the presence or absence of the NPI-Q symptoms. The most distinguishing features between the two groups were anxiety (p=0.0282), apathy (p=0.0217), aberrant motor behavior (p=0.0344) and appetite (p=0.0068). The patients with PPA were 3.5 times more likely to have anxiety and 12.2 times more likely to have appetite abnormalities. However, apathy was 3.2 times and aberrant motor behavior was 9.1 times more likely to be present in patients with PPAOS. Delusions and euphoria were present only in the PPA patients and hallucinations and nighttime behavior abnormalities were present in only 3(2.8%) and 6(5.7%) across both groups. Further details of the multivariate analysis comparing PPA and PPAOS are shown in Table 4.
Table 3.
NPS in PPA and PPAOS
| PPA | PPAOS | p-value | ||
|---|---|---|---|---|
| No of patients | 65(61.3%) | 41(38.7%) | ||
| NPI total | 2.8±2.9 | 2.4±2.3 | 0.5626 | |
| NPI BREAKDOWN | ||||
| Delusion | 0.3737 | |||
| 0 | 63(97%) | 41(100%) | ||
| 1 | 1(1.5%) | 0 | ||
| 2 | 1(1.5%) | 0 | ||
| Hallucination | 0.5815 | |||
| 0 | 63(97%) | 40(97.6%) | ||
| 1 | 1(1.5%) | 1(2.4%) | ||
| 2 | 1(1.5%) | 0 | ||
| Agitation | 0.816 | |||
| 0 | 53(81.6%) | 33(80.5%) | ||
| 1 | 8(12.3%) | 7(17.1%) | ||
| 2 | 3(4.6%) | 1(2.4%) | ||
| 3 | 1(1.5%) | 0 | ||
| Depression | 0.2018 | |||
| 0 | 37(57%) | 28(68.3%) | ||
| 1 | 26(40%) | 10(24.4%) | ||
| 2 | 2(3%) | 3(7.3%) | ||
| Anxiety | 0.288 | |||
| 0 | 41(63.1%) | 32(78%) | ||
| 1 | 17(26.2%) | 8(19.5%) | ||
| 2 | 6(9.2%) | 1(2.4%) | ||
| 3 | 1(1.5%) | 0 | ||
| Euphoria | 0.1593 | |||
| 0 | 63(97%) | 41(100%) | ||
| 1 | 2(3.1%) | 0 | ||
| Apathy | 0.1179 | |||
| 0 | 45(69.2%) | 21(51.2%) | ||
| 1 | 13(20) | 15(36.6%) | ||
| 2 | 7(10.8%) | 4(9.8%) | ||
| 3 | 0 | 1(2.4%) | ||
| Disinhibition | 0.3967 | |||
| 0 | 56(86.1%) | 39(95.1%) | ||
| 1 | 7(10.8%) | 2(4.9%) | ||
| 2 | 2(3.1%) | 0 | ||
| Irritability | 0.5229 | |||
| 0 | 37(57%) | 22(53.7%) | ||
| 1 | 22(33.8%) | 16(39%) | ||
| 2 | 6(9.2%) | 2(4.9%) | ||
| 3 | 0 | 1(2.4%) | ||
| Aberrant motor | 0.1544 | |||
| 0 | 62(95.4%) | 36(87.8%) | ||
| 1 | 2(3.1%) | 4(9.8%) | ||
| 2 | 1(1.5%) | 0 | ||
| 3 | 0 | 1(2.4%) | ||
| Night time behavior | 0.6108 | |||
| 0 | 61(93.9%) | 39(95.1%) | ||
| 1 | 3(4.6%) | 2(4.9%) | ||
| 2 | 1(1.5%) | 0 | ||
| Appetite | 0.0998 | |||
| 0 | 53(81.5%) | 39(95.2%) | ||
| 1 | 9(1.4%) | 1(2.4%) | ||
| 2 | 3(4.6%) | 1(2.4%) | ||
Fig. 1.
Distribution of NPS across PPA and PAOS according to the NPI breakdown.
Table 4.
Multivariate logistic regression analysis for NPI symptoms present or absent between PPA vs PPAOS
| Neuropsychiatric symptoms | OR (95% CI) | p-value |
|---|---|---|
| Delusion | N/A1 | |
| Hallucination | 1.01(0.06–24.3) | 0.9963 |
| Agitation | 1.01(0.28–4.07) | 0.9484 |
| Depression | 1.33(0.49–3.63) | 0.57 |
| Anxiety | 3.55(1.14–12.65) | 0.0282 |
| Euphoria | N/A1 | |
| Apathy | 0.31(0.11–0.84) | 0.0217 |
| Disinhibition | 1.92(0.28–18.61) | 0.5176 |
| Irritability | 0.99(0.37–2.69) | 0.9869 |
| Aberrant motor | 0.11(0.01–0.86) | 0.0344 |
| Night time behavior | 0.37(0.02–5.52) | 0.4717 |
| Appetite | 12.21(1.86–169.45) | 0.0068 |
Not applicable as symptoms were present only in one category
OR: Odds Ratio, CI: Confidence Intervals
When the three subtypes of PPA (agPPA, lvPPA and svPPA) are compared to each other, the most significant differentiating symptoms among them were disinhibition and appetite. Delusion and hallucination were present only in lvPPA whereas aberrant motor abnormalities were not present in this group. The details of NPS according to their severity among the three groups of PPA patients are presented in Table 5.
Table 5.
NPS among different subtypes of PPA
| agPPA | IvPPA | svPPA | p value | ||
|---|---|---|---|---|---|
| No of patients | 15 | 37 | 13 | ||
| NPI Total | 2.5±2.6 | 2.6±2.9 | 3.4±3.5 | 0.6936 | |
| NPI BREAKDOWN | |||||
| Delusion | N/A | ||||
| 0 | 15(100%) | 35(94.6%) | 13(100%) | ||
| 1 | 0 | 1(2.7%) | 0 | ||
| 2 | 0 | 1(2.7%) | 0 | ||
| Hallucination | N/A | ||||
| 0 | 15(100%) | 35(94.6%) | 13(100%) | ||
| 1 | 0 | 1(2.7%) | 0 | ||
| 2 | 0 | 1(2.7%) | 0 | ||
| Agitation | 0.2607 | ||||
| 0 | 13(86.6%) | 30(81.1%) | 10(76.9%) | ||
| 1 | 1(6.7%) | 6(16.2%) | 1(7.7%) | ||
| 2 | 1(6.7%) | 0 | 2(15.4%) | ||
| 3 | 0 | 1(2.7%) | 0 | ||
| Depression | 0.72 | ||||
| 0 | 10(66.7%) | 20(54.1%) | 7(53.8%) | ||
| 1 | 5(33.3%) | 16(43.2%) | 5(38.5%) | ||
| 2 | 0 | 1(2.7%) | 1(7.7%) | ||
| Anxiety | 0.7167 | ||||
| 0 | 11(73.3%) | 23(62.2%) | 7(53.8%) | ||
| 1 | 3(20%) | 10(27%) | 4(30.8%) | ||
| 2 | 1(6.7%) | 4(10.8%) | 1(7.7%) | ||
| 3 | 0 | 0 | 1(7.7%) | ||
| Euphoria | 0.413 | ||||
| 0 | 15(100%) | 36(97.3%) | 12(92.3%) | ||
| 1 | 0 | 1(2.7%) | 1(7.7%) | ||
| Apathy | 0.7525 | ||||
| 0 | 10(66.7%) | 25(67.6%) | 10(76.9%) | ||
| 1 | 4(2.6%) | 8(21.6%) | 1(7.7%) | ||
| 2 | 1(6.7%) | 4(10.8%) | 2(15.4%) | ||
| Disinhibition | 0.0245a | ||||
| 0 | 14(93.3%) | 34(91.9%) | 8(61.5%) | ||
| 1 | 1(6.7%) | 3(8.1%) | 3(23.1%) | ||
| 2 | 0 | 0 | 2(15.4%) | ||
| Irritability | 0.4815 | ||||
| 0 | 8(53.3%) | 19(51.4%) | 10(76.9%) | ||
| 1 | 5(33.3%) | 15(40.5%) | 2(15.4%) | ||
| 2 | 2(13.4%) | 3(8.1%) | 1(7.7%) | ||
| Aberrant motor | 0.0542 | ||||
| 0 | 14(93.3%) | 37(100%) | 11(84.6%) | ||
| 1 | 1(6.7%) | 0 | 1(7.7%) | ||
| 2 | 0 | 0 | 1(7.7%) | ||
| Night time behavior | 0.14 | ||||
| 0 | 13(86.7%) | 36(97.3%) | 12(92.3%) | ||
| 1 | 2(13.3%) | 1(2.7%) | 1(7.7%) | ||
| Appetite | 0.0164b, 0.0092c | ||||
| 0 | 10(66.7%) | 35(94.6%) | 8(61.5%) | ||
| 1 | 4(2.6%) | 2(5.4%) | 3(23.1%) | ||
| 2 | 1(6.7%) | 0 | 2(15.4%) | ||
Significance achieved between lvPPA and svPPA
Significance achieved between agPPA and lvPPA
Significance achieved between lvPPA and svPPA
N/A- not applicable
Discussion
Our study with a large series of patients with PPA and PPAOS, the largest collection of PPAOS cases to date, highlights the behavior differences between PPA and PPAOS and among the three categories of PPAs. Mood symptoms like anxiety and appetite changes are more likely to be present in PPA whereas PPAOS patients are more likely to have behavioral symptoms like aberrant motor behavior and apathy. Among the three categories of PPA, svPPA patients are more likely to show disinhibition while appetite changes are more likely to be present in svPPA and agPPA patients.
Apraxia of speech is a disorder of speech motor planning or programming that affects the production of speech.[13] More recently AOS have been demonstrated in context of neurodegerative disorders.[6,13,14] Hence a syndrome of motor speech impairment as the presenting sign, in absence of aphasia is referred to as PPAOS.[6] The limited recognition of PPAOS disorders until recently could be due to the following factors: 1) it is always difficult to differentiate AOS from aphasias 2) Since it is a recent identity, even patients who were recognized before, were either labelled as either a PPA or dysarthria. In our study, caregivers of PPAOS most commonly endorsed apathy (48.8%), irritability (46.3%), depression (31.7%), anxiety (22%) and agitation (19.5%). The less common symptoms were aberrant motor (12.2%), nighttime behavior abnormalities (4.9%), appetite changes (4.9%) and disinhibition (4.9%). Delusion and euphoria were not present in any of our patients. PPAOS patients are therefore more likely to demonstrate behavior abnormalities like apathy and aberrant motor abnormalities as compared to PPA patients. These findings are not unexpected as PPAOS has often been linked to progressive supranuclear palsy (PSP) pathology [15] and profound apathy is often a common and supportive feature of PSP.[16,17] PPAOS patients also demonstrate midbrain atrophy, which is a feature of pathologically confirmed PSP.[18,19] This correlation has been further quantified in a recent study showing the evolution of PPAOS, which demonstrated that these patients may progress to PSP like syndrome referred as PSP-AOS.[20]
There have been some studies looking at the NPS of PPA patients.[7–10] However, none of them had compared the various subtypes of PPA according to the latest classification. In our cohort of PPA patients, the most common presentation was lvPPA (56.9 %%). The earliest age of onset of PPA was in svPPA (61.7±6.5 yrs.) whereas agPPA patients presented earliest to the hospital (2.3 ±1.4 yrs.). Differentiating symptoms among the three subtypes of PPA were disinhibition (0.0245) and appetite changes (0.006). Disinhibition was more likely to be present in semantic PPA compared to the other two subtypes. Interestingly, although disinhibition is most common in svPPA compared to the other PPA variants and PPAOS, it has been shown to be less common in semantic dementia compared to behavioral variant of frontotemporal dementia. [21] The appetite changes were highly significant among the three groups with svPPA patients and agPPA patients more likely to present with these changes. Depression was present in 43% of PPA patients with the lvPPA diagnosis encompassing the majority of the patients (60.7%). Depression has also been observed in PPA patients. [1,22,23] Interestingly, depression was present in four of the six PPA patients that were first reported by Mesulam in 1982.
In our study, delusion and hallucinations were present in only lvPPA among the PPA patients. This is a novel finding and could be due to the fact that lvPPA has been linked to the Alzheimer’s disease pathology which can co-occur with Lewy body disease. [24] Lewy body disease is strongly associated with hallucinations. In fact in a recent clinicopathological series, mixed Alzheimer’s and Lewy body disease was reported in 8% of cases of lvPPA [25]
Some researchers have suggested that PPAOS should not be considered different from patients with non-fluent/agrammatic PPA although we have clearly demarcated that PPAOS is anatomically different from agrammatic PPA with involvement of the bilateral superior and mid premotor cortex,[6] in contrast to agrammatic PPA which affects the left posterior frontoinsular cortex.[2] The findings of this study further strengthen the argument of segregating them as the patients with PPA were more likely to have mood symptoms like anxiety and appetite changes while PPAOS patients are more likely to have behavioral symptoms like aberrant motor behavior and apathy.
The type of behavioral symptoms changed overtime with longer disease durations. Patients with both PPA and PPAOS showed symptoms initially inclined towards mood disorders like depression. This may be related to an emotional response towards the disease affecting their daily communication capabilities. However, with the increase in disease duration, the PPAOS patients more likely showed apathy (55.5%) while the PPA patients more likely showed disinhibition (28.6%) and aberrant motor behavior (14.3%).The PPA symptoms present in the initial 5 years, and those that develop after that, are consistent with previous reports.[7] These findings suggest that as PPA progresses; the neurodegenerative process expands and eventually involves the brain regions affecting behavior, such as the frontal lobe. [2,18,26] Another interesting finding, not previously reported was the fact that some of the behavioral symptoms present early in the disease (< 5 years) appeared to resolve over time. For example, aberrant motor behaviors while present in 15.6% of the PPAOS subjects < 5 years after onset were no longer present after 5 years illness duration. The details of the NPS present before and after 5 years, for both PPAOS and PPA are shown in Table 6.
Table 6.
NPS according to disease duration
| PPA | PPAOS | |||||
|---|---|---|---|---|---|---|
| SDa(n=51) | LDb(n=14) | p-value | SD(n=23) | LD(n=9) | p-value | |
| Delusion | 1(1.9%) | 1(7.1%) | 0.3670 | 0 | 0 | N/A |
| Hallucination | 2(3.9%) | 0 | 0.3203 | 1(3.1%) | 0 | 0.4783 |
| Agitation | 9(17.6%) | 3(21.4%) | 0.7501 | 7(21.9%) | 1(11.1%) | 0.4491 |
| Depression | 24(47.1%) | 4(28.6%) | 0.0431 | 10(31.2%) | 3(33.3%) | 0.9058 |
| Anxiety | 18(35.3%) | 6(42.9%) | 0.6060 | 7(21.9%) | 2(22.2%) | 0.9823 |
| Euphoria | 2(3.9%) | 0 | 0.3203 | 0 | 0 | N/A |
| Apathy | 18(35.3%) | 2(14.3%) | 0.1114 | 15(46.9%) | 5(55.5%) | 0.0472 |
| Disinhibition | 5(9.8%) | 4(28.6%) | 0.0358 | 1(3.1%) | 1(11.1%) | 0.3700 |
| Irritability | 22(43.1%) | 6(42.9%) | 0.9850 | 15(46.9%) | 4(44.4%) | 0.8971 |
| Aberrant motor | 1(1.9%) | 2(14.3%) | 0.0439 | 5(15.6%) | 0 | 0.0212 |
| Night time behavior | 3(5.9%) | 1(7.1%) | 0.8643 | 1(3.1%) | 1(11.1%) | 0.3700 |
| Appetite | 8(15.7%) | 4(28.6%) | 0.2903 | 1(3.1%) | 1(11.1%) | 0.3700 |
SDa-Short duration (<5 years)
LDb-Long duration (≥5 years)
N/A- not applicable
The NPS associated with both PPA and PPAOS may have treatment implications for the physicians, patients and their caregivers. With better knowledge of the NPS associated with these neurodegerative disorders, appropriate psychosocial education and support can be outlined for both the patients and the caregivers and may help to equip them in handling the behaviors. Patients with PPA might also have emotion recognition disturbances which are mediated by attentional deficits.[27] Hence with a better knowledge of the relationship between illness duration and the appearance of a specific NPS, physicians are better able to discuss long term outcomes and treatment options.
This study has some limitations. Although there have been studies showing the reliability and validity of NPI-Q, [11,12] the NPI-Q is a brief measure of symptom assessment asking just 1 question per symptom domain. The simple and brief nature of NPI-Q may not necessarily capture the nuances of some particularly complex symptoms, particularly during the earlier stages of the illness. For example, it is difficult to know whether patients presenting with mild depression/anxiety is due to an emotional response secondary to language impairment, or to a noncognitive manifestation of the neurodegenerative process. Another limitation is that the estimation of disease duration is subjective and we could not follow the progression of behavior symptoms. Hence further studies are needed to access the potential mechanisms linking NPS with these disorders and long term follow up of subtypes of PPA and PPAOS patients may help in understanding the natural history and evolution of their NPS.
In conclusion, the result of this study highlights the differences in the NPS between the two categories of neurodegenerative speech disorders, PPAOS and PPA and among different subtypes of PPA patients. Mood symptoms like anxiety and appetite changes are more likely to be present in initial stages of PPA whereas behavioral symptoms like aberrant motor behavior and apathy are likely to occur in PPAOS. Additionally, it appears that NPS evolve with the progression of the disease and may not always be present. A better understanding of the NPS among these groups of patients helps to better outline a treatment strategy for both the patient and the caregiver.
Acknowledgments
STUDY FUNDING
Supported by NIH R01-DC010367
J. Duffy is a coinvestigator for R01-DC012519 and R01-DC010367. E. Strand is a coinvestigator for R01-DC012519 and R01-DC010367. M. Machulda is funded by R01-AG037491 (Co-I), R01-DC012519 (Co-I), and the Alzheimer's Association (Co-I). J. Whitwell is funded by R01-DC012519 (PI), R01-DC010367 (Co-I), R01-AG037491 (Co-I), and the Alzheimer's Association (PI). K. Josephs is funded by NIH R01-DC010367 (PI), R01-AG037491 (PI), R01-DC012519 (Co-I), and the Alzheimer's Association (Co-I).
Footnotes
AUTHOR CONTRIBUTIONS
Dr Josephs had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Josephs, Duffy, Strand
Acquisition, analysis, or interpretation of data: Singh, Josephs, Duffy, Strand, Machulda, Whitwell
Drafting of the manuscript: Singh, Josephs
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Singh, Josephs
Obtained funding: Josephs
Study supervision: Josephs, Duffy, Strand
CONFLICT OF INTEREST DISCLOSURES
T. Singh reports no disclosures.
References
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