Martin, Peter R.

BACKGROUND: Parkinson’s disease (PD)-associated psychosis is a well-known non-motor complication, occurring years after diagnosis of PD. Incidence data vary across different studies highlighting a need for long-term observation and clinical definition. OBJECTIVE: To determine the incidence of psychosis in patients with PD and to investigate their survival in an incident cohort study from 1991–2010 in Olmsted County, MN. METHODS: We used the Rochester Epidemiology Project to define an incident-cohort study of parkinsonism (1991–2010) in Olmsted County, MN. A movement-disorder specialist reviewed the electronic medical records and applied diagnosis criteria to PD. Psychosis was diagnosed using of NINDS/NIMH unified criteria. RESULTS: We identified 669 cases of parkinsonism; 297 patients were clinically diagnosed with PD. 114/297 (38.4%) patients had evidence of psychosis (60% male); the median onset age of psychosis was 79.4 years. The incidence of Parkinson’s disease psychosis (PDP) was 4.28/100 person-years. PDP patients had a 71% increased risk of death compared to PD patients. In PD patients without psychosis, men had 73.4% increased risk of death compared to women, whereas no significant sex difference was observed among PDP men vs. women. Of 114 patients diagnosed with psychosis, 59 were treated with antipsychotics. There was no significant difference in survival between treated and untreated patients. CONCLUSION: PDP increased the odds of death compared to PD patients. Men with PD without psychosis had greater odds of death compared to women; however, in PD with psychosis the odds of death were comparable among sexes. Lastly, treatment with anti-psychotics did not significantly affect survival.

AbstractBackgroundIndividuals with Primary Progressive Apraxia of Speech (PPAOS) have AOS as the initial and predominant symptom. Many develop aphasia and/or dysarthria later in the disease course. Past research has shown that patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co‐occurring language deficits. Previous studies suggest measures of disease severity do not necessarily correlate with measures of participation restrictions. The aim of this study was to describe changes in communication limitations in these patients over a one‐year interval, measured by 1) the patient via the Communicative Participation Item Bank (CPIB) and 2) the speech‐language pathologist via ASHA's Functional Communication Measures (FCMs) and an adapted Motor Speech Disorder (MSD) severity rating and determine if there are significant changes in these and other objective speech and language measures (e.g. Western Aphasia Battery‐Revised Aphasia Quotient, Apraxia of Speech Rating Scale‐3).MethodSeventeen patients (10 male) with progressive AOS were seen for a second visit approximately one year following the first visit. The measures collected at each visit were statistically compared. Correlations were calculated between the participation ratings and other clinical assessment measures at each visit and qualitatively compared.ResultThere were statistically significant differences in AOS and aphasia severity between visits. There were significant changes in clinical assessments, MSD severity rating, and all ASHA FCMs between visits, but not the CPIB. Comparison of correlations suggest the relationships among clinical and participation measures may change over time.ConclusionThe findings of this study support the use of patient reported outcome measures, like the CPIB, as they may better reflect the patient experience and associated changes in day‐to‐day functioning when other measures may simply index the progression of the disease.

AbstractBackgroundThe Neurodegenerative Research Group (NRG) at Mayo clinic has followed patients with degenerative speech and/or language disorders for over a decade. In this presentation I will present data from this cohort to inform a broader discussion about the importance of apraxia of speech (AOS) and its subtypes, heterogeneity within the agrammatic PPA variant, and perils of mixed phenotypes.MethodWe reviewed the NRG database to identify patients who initially presented with isolated (PPAOS), AOS in conjunction with agrammatic aphasia (AOS‐PAA), isolated agrammatic aphasia (PAA), and patients who had PAA or AOS overlapping with another degenerative diagnosis. Data from the following clinical instruments were abstracted: WAB AQ (aphasia severity), UPDRS III (parkinsonism), WAB Praxis (ideomotor apraxia), and the MoCA (cognitive ability). We assessed the effect of baseline diagnosis and AOS subtype on these outcomes over time using Bayesian linear mixed effects models. We qualitatively reviewed longitudinal diagnostic trajectories. Preliminary analyses were done on available autopsy data.ResultPAA was associated with greater aphasia at baseline and more rapid decline; PPAOS was associated with normal language at baseline and slow decline; and PAA‐AOS with intermediate baseline aphasia and decline. However, for those with AOS longitudinal decline differed based on AOS subtype: prosodic PPAOS was associated with the slowest decline and phonetic PAA‐AOS with the fastest. Some patients met criteria for non‐PPA disorders during follow up. However, compared to patients who met criteria for these disorders at enrollment, the speech/language‐first patients remained qualitatively distinct, and neither resembled the cases that were mixed at onset. Preliminary autopsy data suggests that AOS is predictive of tau and that the specific tauopathy may be related to the initial syndrome and AOS subtype.ConclusionThe differences between PAA, PAA‐AOS and PPAOS suggest that these disorders should not be lumped. In fact, the longitudinal trajectories are sufficiently different that doing so would add noise to observational and interventional studies. Instead, more detailed phenotyping, including AOS subtype, can aid prognostication and may improve prediction of the underlying pathology. Finally, caution should be exercised when considering PPAOS and PPA patients for other FTLD diagnostic categories.

AbstractBackgroundLogopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA) have distinct patterns of hypometabolism and atrophy. However, these clinical syndromes overlap: visuospatial impairment has been documented in LPA and aphasia in PCA. Rey‐Osterrieth Complex Figure – Copy (Rey‐O Copy) performance is correlated with parietal‐occipital atrophy in LPA. We explore visuospatial impairment on the Rey‐O Copy in LPA and PCA with the Mayo Older Americans Normative Studies (MOANS; which uses Meyers & Meyers criteria) and the Boston Qualitative Scoring System (BQSS). We also examine the proportion of visuospatial impairment in LPA, an under‐appreciated phenomenon, compared to PCA wherein it is fundamental.MethodPatients with LPA (n=25) or PCA (n=23) were recruited by the Neurodegenerative Research Group. Patients underwent comprehensive neuropsychological testing (including Rey‐O Copy) at baseline visit. Cut‐offs of T‐score=40 (BQSS) or scaled score=7 (MOANS) were used based on normative data. Proportions of patients with low performance were examined across LPA and PCA groups. Individual logistic regressions and AUROC analyses were then conducted to quantify differences in visuospatial impairment in LPA and PCA with both scoring systems. Identical analyses were conducted using raw scores corrected for age and sex, to avoid confounds of adjustments in normative data.ResultLPA and PCA groups were comparable on age, sex, and disease duration (LPA Median = 2.7 years, IQR=1.9‐3.5; PCA Median = 3.6 years, IQR=1.5‐4.9); p=.823). Surprisingly, 52‐72% of LPA participants demonstrated impaired performance across scoring systems, relative to 96% of the PCA group identified by both scoring systems. Odds ratios (OR) for the Rey‐O Copy MOANS (OR = 1.59; p=.008) and BQSS Copy Presence and Accuracy index (CPA; OR = 1.13, p=.002) were significant, persisting for age‐ and sex‐ controlled raw scores, suggesting the odds of a PCA diagnosis increased with decrement on Rey‐O Copy. AUROC values ranged from 0.77 to 0.88 across these indices.ConclusionA substantial number of LPA participants showed visuospatial impairment, despite initial primary language complaints. Differentiation of diagnostic groups by the Rey‐O is likely underscored by relatively uniform, profound, visuospatial impairment in PCA with more variability in LPA. However, the degree of visuospatial impairment overlaps remarkably across diagnoses.

AbstractBackgroundMagnetic resonance brainstem measurements are useful structural biomarkers in the Richardson's syndrome variant of progressive supranuclear palsy (PSP). However, it is unclear how these biomarkers differ across the phenotypic spectrum of PSP and how they relate to underlying pathology.ObjectiveThe aim of this study was to compare brainstem imaging measures across clinical variants of PSP and determine sensitivity and specificity based on pathologically diagnosed cases.MethodsA total of 153 patients with PSP who represented eight clinical variants were recruited at Mayo Clinic (Rochester, MN, USA) and underwent structural magnetic resonance imaging (MRI). Midbrain and pons area and superior and middle cerebellar peduncle width measurements were performed, and midbrain/pons ratio and Magnetic Resonance Parkinsonism Index (MRPI) were calculated. Among the 43 patients who later died, PSP pathology was confirmed in 29, whereas 14 had other pathology.ResultsBrainstem measurements varied across PSP clinical variants and were most abnormal in PSP‐Richardson's syndrome and frontal variants, followed by PSP‐corticobasal, PSP‐speech/language, and PSP‐parkinsonism variants. All these variants showed abnormalities compared with controls. The PSP‐gait freezing variant and patients with prominent corticospinal tract signs showed normal brainstem measures. Among cases with confirmed PSP pathology, the midbrain area, midbrain/pons ratio, and MRPI were all more abnormal compared to those with other pathologies, with best differentiation obtained with the MRPI (sensitivity = 83%; specificity = 85%).ConclusionsMRI brainstem measures show utility as diagnostic biomarkers across PSP clinical variants and have the potential to be useful in predicting underlying pathology. © 2021 International Parkinson and Movement Disorder Society

Purpose Individuals with primary progressive apraxia of speech have apraxia of speech (AOS) as the initial and predominant symptom. Many develop aphasia and/or dysarthria later in the disease course. It was previously demonstrated that patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co-occurring language deficits ( Utianski et al., 2020 ). Measures of disease severity did not necessarily correlate with measures of participation restrictions. The aim of this follow-up study was to describe changes in communication limitations in these patients, again measured by (a) the patient via the Communicative Participation Item Bank (CPIB) and (b) the speech-language pathologist via the American Speech-Language-Hearing Association's (ASHA's) Functional Communication Measures (FCMs) and an adapted motor speech disorder (MSD) severity rating to determine if there are significant changes in these and other objective speech and language measures at follow-up after 1 year. Method Of the 24 patients reported in the study of Utianski et al. (2020) , 17 (10 men, seven women) returned for a second visit approximately 1 year following the first visit. Identical procedures were utilized; the communication measures collected at each visit were statistically compared. Correlations were calculated between the participation ratings and other clinical assessment measures at the second visit and for the change in scores on those measures between the first and second visits. Results There were statistically significant differences in AOS and aphasia severity between visits. There were significant changes in clinical assessments, MSD severity rating, and all ASHA FCMs between visits, but not the CPIB. Correlation analyses suggest the relationships among clinical and participation measures are complex; overall, patients with more severe changes in AOS experienced greater changes in participation restrictions. Conclusions The findings of this study support the use of patient-reported outcome measures as they may better reflect the patient experience, including the influence of factors such as ongoing speech therapy and the emergence of neuropsychiatric features, and associated changes in day-to-day functioning, when other measures may simply index the progression of the disease. Supplemental Material https://doi.org/10.23641/asha.16528512

Purpose Individuals with primary progressive apraxia of speech (PPAOS) have apraxia of speech (AOS) in which disruptions in articulation or prosody predominate the speech pattern, referred to, respectively, as phonetic or prosodic subtypes. Many develop aphasia and/or dysarthria. Past research has demonstrated that simple temporal acoustic measures are sensitive to the presence of AOS. The aim of this study was to describe the change in temporal acoustic measures over time and assess if specific patterns of AOS or co-occurring aphasia or dysarthria impact the rate of change over time. Method Durations for multiple productions of the words cat , catnip , catapult , and catastrophe , in an imitative speech task, were recorded for 73 patients, with two to six visits each. A linear mixed-effects model was used to assess the cross-sectional differences and longitudinal influence of AOS subtype and presence of aphasia/dysarthria on speech rate. Pearson correlations were calculated between rate measures and performance on other clinical measures. Results Cross-sectionally, patients with prosodic-predominant PPAOS produced words more slowly than those with phonetic-predominant PPAOS. Patients with either aphasia or dysarthria produced words more slowly than those without. Longitudinally, the speech rate of patients with phonetic-predominant PPAOS had a reduction of 0.5 syllables per second per year. Patients with prosodic-predominant AOS changed less quickly, as did those who developed aphasia. Dysarthria did not impact rate of change. There were strong associations between speech rate measures and other clinical indices of speech and language functioning. Conclusion Simple temporal acoustic measures may reflect the subtype of AOS (phonetic or prosodic predominant), serve as an index of progression of AOS, and inform prognostication relative to the presenting combination of speech and language features. Supplemental Material https://doi.org/10.23641/asha.13564724

ObjectiveThe aim was to analyze the timeline, prevalence, and survival of rapid eye movement (REM) sleep behavior disorder (RBD) in patients who developed alpha‐synucleinopathies (Parkinson disease, dementia with Lewy bodies, and Parkinson disease dementia) compared with age‐ and sex‐matched controls in a population‐based incident‐cohort study.MethodsWe used a population‐based, 1991 to 2010 incident‐cohort study of alpha‐synucleinopathies. A movement‐disorder specialist reviewed medical records to confirm diagnoses. RBD was diagnosed by reported dream‐enactment symptoms or polysomnography. Probable RBD and polysomnographically confirmed RBD were analyzed separately and combined.ResultsAmong the 444 incident cases of alpha‐synucleinopathy, 86 were clinically diagnosed with RBD (19.8%), including 30 (35%) by polysomnography and 56 (65%) as probable. The prevalence of idiopathic RBD at alpha‐synucleinopathy diagnosis was 3.4%, increasing to 23.8% after 15 years. Cumulative lifetime incidence was 53 times greater in alpha‐synucleinopathy patients than in controls (odds ratio [OR] = 53.1, 95% confidence interval [CI]: 13.0–217.2, p < 0.0001), higher in dementia with Lewy bodies than in Parkinson disease (OR = 2.57, 95% CI: 1.50–4.40, p = 0.0004), and higher in men than in women with Parkinson disease, dementia with Lewy bodies, or Parkinson disease dementia (OR = 3.70, 95% CI: 2.07–6.62, p < 0.0001), but did not increase mortality risk.InterpretationOur cohort had RBD incidence of 3.4%. Overall RBD increased to 23.8% after 15 years, with an overall incidence of 2.5 cases per 100 person‐years. With 53 times greater lifetime incidence in alpha‐synucleinopathy patients than in controls, RBD was more likely to develop in dementia with Lewy bodies than in Parkinson disease or Parkinson disease dementia, and in men than in women, but did not increase mortality risk within our cohort. ANN NEUROL 2021;89:293–303

AbstractThe mechanisms through which tau and amyloid-beta (Aβ) accumulate in the brain of Alzheimer’s disease patients may differ but both are related to neuronal networks. We examined such mechanisms on neuroimaging in 58 participants with atypical Alzheimer’s disease (posterior cortical atrophy or logopenic progressive aphasia). Participants underwent Aβ-PET, longitudinal tau-PET, structural MRI and resting-state functional MRI, which was analyzed with graph theory. Regions with high levels of Aβ were more likely to be functional hubs, with a high number of functional connections important for resilience to cascading network failures. Regions with high levels of tau were more likely to have low clustering coefficients and degrees, suggesting a lack of trophic support or vulnerability to local network failures. Regions strongly functionally connected to the disease epicenters were more likely to have higher levels of tau and, less strongly, of Aβ. The regional rate of tau accumulation was associated with tau levels in functionally connected regions, in support of tau accumulation in a functional network. This study elucidates the relations of tau and Aβ to functional connectivity metrics in atypical Alzheimer’s disease, strengthening the hypothesis that the spread of the 2 proteins is driven by different biological mechanisms related to functional networks.