Kantarci, Kejal

Abstract Introduction Patients with Parkinson’s disease commonly underreport sleep symptoms, but the extent to which such mismatch may be present in people with isolated RBD (iRBD) is unknown. We evaluated how the patient–bedpartner (PT–BP) mismatch in night-time and daytime sleep complaints relates to cognition, apathy, dopaminergic degeneration, and cortical structure in iRBD. Methods We retrospectively analyzed 425 iRBD participants (2018–2025) from the North American Prodromal Synucleinopathy (NAPS) Consortium with clinicodemographic data, dopamine transporter (DAT) imaging, and magnetic resonance imaging. Using Scales for Outcomes in Parkinson’s Disease (SCOPA)-Sleep, PT–BP mismatch was classified into overestimator (PT>BP), concordant (PT=BP), and underestimator (PT< BP) groups, separately for complaints during night and day. Outcomes included cognition (CDR-Sum of Boxes [CDR-SB], CDR-global, and individual subdomain tests), pareidolia, apathy, subregional DAT uptake, and cortical thickness. Group differences were tested with analysis of covariance adjusting for age, sex, disease duration, education, clinician-rated OSA treatment inadequacy, and the corresponding patient-reported SCOPA-Sleep domain (night or day), and estimated total intracranial volume for cortical thickness; pairwise tests used Bonferroni correction. Results The PT–BP mismatch was common (night – overestimator 127/425, 29.9% and underestimator 116/425, 27.3%; day – overestimator 77/425, 18.1% and underestimator 134/425, 31.5%). For night-time mismatch, underestimators showed lower CDR-SB and lower CDR-global than overestimators. In addition, underestimators exhibited more illusory responses, fewer correct noise rejections, and fewer total correct responses than overestimator and concordant groups. For daytime mismatch, CDR-SB was lower in underestimators versus overestimators; CDR-global was lower in underestimators and concordant participants versus overestimators. No significant associations were found for apathy. Subregional DAT uptake did not differ by mismatch group. Cortical thickness analyses revealed thinner right transverse gyrus in underestimator and concordant groups compared to the overestimator group and thinner left superior temporal gyrus in underestimator group compared to overestimator group, for night-time mismatch only. Conclusion The PT–BP subjective sleep mismatch can be used as a clinical marker associated with overall cognitive decline and cortical thinning in auditory and language processing areas, which may underlie impairment in perceptual interpretation and hallucination proneness. Further research is warranted to seek longitudinal change and phenoconversion in mismatch groups. Support (if any) #U19-AG071754 (NAPS Consortium)

Abstract INTRODUCTION Alzheimer's disease neuropathologic change (ADNC) classification identifies not/low and intermediate/high levels of neuropathology. Our goal was to assess how frequently a positive amyloid positron emission tomography (PET) scan indicates not/low ADNC and whether this autopsy finding can occur >10 years after a positive amyloid PET. METHODS Participants with positive amyloid PET scans were categorized by levels of ADNC at autopsy, grouped by time from initial positive amyloid PET to time of death (<5 years, 5 to <10 years, or 10+ years). RESULTS Among those with a positive amyloid PET scan, the majority had intermediate/high ADNC at autopsy (234/259, 90%). In the group with 10+ years between a positive amyloid PET and death ( n = 39) not/low ADNC occurred in 3/39 (8%). DISCUSSION Not/low ADNC is uncommon among those with positive amyloid PET scans. After 10+ years, it is possible but rare for a positive amyloid PET scan to represent an indolent state of neuropathology.

Abstract INTRODUCTION Visual perceptual difficulties occur in dementia with Lewy bodies (DLB). Normative data and cut scores for DLB and mild cognitive impairment with Lewy bodies (MCI‐LB) are needed for the 20‐item Noise Pareidolia Task. METHODS Participants included 344 cognitively unimpaired (CU), 112 DLB, and 105 MCI‐LB. Cumulative percentile ranking was used for normative classification. Receiver operating characteristic analyses, convergent validity, and associations with visual hallucinations (VH) were assessed. RESULTS In CU participants, a perfect score was average, one error was low average, and two or more errors fell below average. A cut score of one or more errors optimally distinguished CU participants from DLB (Total score area under the curve [AUC]: 0.82, Noise score AUC: 0.77) and MCI‐LB (Total score AUC: 0.75, Noise score AUC: 0.74). A cut score of two or more errors lowered sensitivity but increased specificity to 94%. Performance was associated with VH in DLB, but not MCI‐LB. DISCUSSION Results establish normative data for the 20‐item Noise Pareidolia Task and support its use in DLB and MCI‐LB.

Introduction Neurological post-acute sequelae of COVID-19 (neuroPASC) are associated with persistent cognitive dysfunction and quality-of-life decline. We aimed to identify clinical, behavioral and sociodemographic factors associated with neuroPASC symptom burden two years after COVID-19 among individuals without prior neurological disease. Methods In this prospective, observational study, individuals with neuroPASC ( n = 102) and controls without symptomatic COVID-19 ( n = 74), all without prior neurological, psychiatric, or post-viral conditions, were enrolled between February 2022 and June 2024 across five academic sites. An unsupervised algorithm identified clusters with differing self-reported neurological symptom burden within the neuroPASC group. Functional differences between clusters were evaluated using quality-of-life, neurological and cognitive evaluations. Demographics, behavioral history, comorbidities, and blood biomarkers were compared across clusters and controls. Multivariable logistic regression assessed predictors of neuroPASC severity, including demographics, body-mass-index, Charlson Comorbidity Index, Framingham Risk Score, pre-existing endocrine/metabolic and/or gastrointestinal/hepatobiliary conditions, COVID-19 vaccination prior to infection, hospitalization during acute infection, and cumulative alcohol use. Results Two clusters emerged based on neurological symptom burden, labeled “high-burden” and “low-burden” neuroPASC, reflecting differences in the number and frequency of symptoms. Both clusters had deficits in quality-of-life and cognitive function compared to controls, with greater impairment in high-burden than low-burden neuroPASC. The clusters did not differ by sex, education, tobacco and cannabis use, blood pressure, body-mass-index, HbA1C, days since infection, hospitalization during COVID-19, pre-COVID vaccination rate, antibody-positivity, inflammation, and neurodegeneration biomarkers. The high-burden cluster was older and exhibited higher comorbidity burden and greater cumulative alcohol use compared with the low-burden cluster and controls. Pre-existing endocrine/metabolic and gastrointestinal/hepatobiliary conditions were more common in high-burden (63%) than in low-burden neuroPASC (35%). After adjusting for clinical and demographic factors, these pre-existing conditions remained the only independent predictor of severity, conferring a 3.5-fold increase in the odds of high-burden versus low-burden neuroPASC. Discussion Older age, higher comorbidity burden, greater cumulative alcohol use, and endocrine/metabolic and gastrointestinal conditions, rather than acute COVID-19 severity, were observed in the high-burden neuroPASC cluster. After multivariable adjustment, only pre-existing endocrine/metabolic and/or gastrointestinal/hepatobiliary conditions remained independently associated with high-burden neuroPASC, conferring a 3.5-fold increase in odds and highlighting the need for targeted post-infection monitoring in at-risk patients.