👤 Aaron Bonner-Jackson

Alzheimer's disease pathology (ADP) and Lewy body pathology (LBP) are traditionally associated with distinct cognitive profiles. However, growing evidence highlights the role of behavioral and psychological symptoms of dementia (BPSD) in shaping clinical presentations. The combined influence of cognitive and behavioral symptoms across neuropathologically confirmed ADP, LBP, and mixed AD-LBP has not been systematically examined. This study aimed to identify clinically meaningful subtypes by jointly analyzing cognitive performance and BPSD profiles in individuals with autopsy-confirmed dementia pathology. This retrospective longitudinal cohort study used data from the National Alzheimer Coordinating Center (NACC), collected across multiple U.S. Alzheimer's Disease Research Centers. Participants had a Clinical Dementia Rating (CDR) Global score ≤1 at baseline and autopsy-confirmed ADP, LBP, or mixed AD-LBP. Cognitive outcomes included standardized tests of memory, executive function, and language. BPSD were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q), which captures ten symptom domains: agitation, apathy, depression, delusions, disinhibition, auditory and visual hallucinations, irritability, personality change, and REM sleep behavior disorder. Cluster analysis was applied to identify subtypes based on combined cognitive and BPSD data. The study included 1,028 participants (mean age at baseline 76.4 years; 47.6% female): 521 with ADP, 96 with LBP, and 411 with mixed AD-LBP. A three-cluster clinical subtype (CS) solution best fit the data. The most symptomatic group (CS-3) had the youngest age at first visit (mean 72.1 years), the highest BPSD burden, and the fastest cognitive and functional decline across ADP and AD-LBP groups. CS-1 and CS-2 exhibited milder early cognitive impairment and lower BPSD burden. Within ADP and AD-LBP, CS-2 showed slower progression than CS-1, fewer APOE ε4 carriers (41% vs. 58%), and better memory scores, despite reporting a higher frequency of agitation. These findings reveal distinct clinical subtypes that cut across traditional pathological boundaries, emphasizing the need to incorporate both cognitive and behavioral features into early dementia characterization. This multidimensional approach can improve guide personalized prognosis and care planning and enhance clinical trial design by considering disease heterogeneity. The study supports integrated clinical profiling as important factor in robust evaluation of dementia outcomes. Show less

BackgroundLogopenic primary progressive aphasia (LPA) is often associated with Alzheimer's disease (AD) pathology. However, few studies have compared cortical atrophy patterns in LPA and AD and their association with cognitive performance.ObjectiveTo identify atrophy patterns specific to LPA and determine whether those patterns relate to deficits in specific cognitive domains.MethodsElectronic health records from 2014-2024 were retrospectively reviewed to identify patients with LPA who had undergone MRI and neuropsychological (NP) examinations. Patients with LPA (n = 26) were matched in terms of age, sex, education, and symptom duration to patients with amnestic mild cognitive impairment (aMCI; n = 13). Logistic regression was used to assess group differences in MRI measures of cortical volume and thickness. Cluster analysis was used to identify patterns of atrophy that were associated with specific cognitive domains.ResultsThe LPA group performed significantly worse than the aMCI group on NP measures assessing verbal learning, attention/working memory, language, and executive functioning (p < 0.05). Compared to the aMCI group, the LPA group demonstrated both smaller and thinner cortex in the left lateral aspect of the superior temporal gyrus, superior temporal sulcus, and fusiform gyrus (p < 0.05), with the left superior temporal sulcus providing the most accurate measure of discrimination. Severity of language related cognitive deficits was not associated with a specific cluster in the LPA group.ConclusionsPatients with LPA demonstrate specific patterns of cortical atrophy that are distinguishable from atrophy due to aMCI and may be useful for diagnostic purposes. Show less