Neuropsychological Profile and Cognitive Trajectories of Patients With Biomarker Evidence of Alzheimer Disease or Dementia With Lewy bodies.

BACKGROUND AND

objectivesAlzheimer disease (AD) and dementia with Lewy bodies (DLB) often coexist, yet the cognitive effect of mixed AD and α-synuclein pathology in vivo remains unclear. We aimed to (1) characterize baseline neuropsychological profiles, (2) assess plasma biomarker associations, and (3) examine longitudinal cognitive trajectories in patients with AD, DLB, and mixed pathology in a memory clinic cohort.

methodsThis was a retrospective longitudinal study including participants from an academic memory clinic cohort with available CSF and blood samples at baseline who completed a comprehensive cognitive assessment. Baseline neuropsychological performance was compared between groups using analysis of covariance controlling for age, sex, and education. Associations between plasma biomarkers and cognition were examined using multiple linear regression models. Linear mixed-effects models examined longitudinal change across groups, with time from baseline, diagnosis, the diagnosis-by-time interaction, baseline age, sex, and years of education as fixed effects, and intercept as a random effect.

resultsA total of 350 participants (mean age 70.1 ± 6.6 years; 48.6% female) were included: AD alone (n = 249), AD with α-synuclein pathology (n = 31), DLB alone (n = 33), and DLB with AD pathology (n = 37). At baseline, patients with AD showed greater impairment than those with DLB in memory and language (all DISCUSSION: Distinct neuropsychological profiles and trajectories emerge in AD and DLB depending on underlying pathology. Identifying mixed pathology in vivo is clinically relevant for accurate diagnosis and prognosis and has implications for outcome measures and patient stratification in clinical trials.