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• W2537446510 abstract "Unlike sporadic Alzheimer’s disease (AD), the age when overt cognitive decline occurs is highly predictable in autosomal dominant AD (ADAD). However, longitudinal cognitive performance in the preclinical and early symptomatic stages of ADAD has not been well characterized. Using data from the Dominantly Inherited Alzheimer Network (DIAN), we explored how trajectories of cognitive performance in ADAD were related to symptom onset and clinical status, and determined whether rates of cognitive decline differed between specific mutations. We also examined trajectories among mutation carriers who enrolled as asymptomatic but progressed to clinically symptomatic. Data from 200 DIAN participants who completed 2-5 cognitive assessments over a mean of 2.8 years of follow-up were used in analyses. Twenty cognitive tests formed a global cognitive composite derived from 5 domain-specific composites representing episodic memory, attentional control, working memory/visuospatial ability, processing speed, and semantic memory. Cognition was modeled with mixed effects regression using estimated year of symptom onset (EYO) as the time scale. Rates of cognitive decline were compared between non-mutation carriers (NCs, n=70) and mutation carriers (MCs, n=130). To determine if decline was evident prior to clinical diagnosis, MCs were subdivided using baseline CDR status into asymptomatic MCs (ASYMCs, n=66) and symptomatic MCs (SYMCs, n=64). MCs demonstrated rapid rates of decline across every domain of cognitive functioning. Compared to NCs, MCs declined an average of 0.05 to 0.09 SDs for every 1-year increase in EYO. ASYMCs showed trends for declines on episodic memory compared to NCs. Post hoc analyses on individual episodic memory measures revealed significant declines in ASYMCs on word list memory, but not associative memory or narrative recall. Cognitive trajectories were similar between APP, PSEN1, and PSEN2 MCs. Thirteen participants enrolled as ASYMCs progressed to CDR >0 at a mean EYO of -2.2 +/-4 years. Progressors declined more rapidly than non-progressor ASYMCs and NCs on episodic memory, attentional control, and processing speed. MCs exhibit widespread cognitive decline that accelerates rapidly in proximity to EYO. Early declines are evident in some, but not all, aspects of episodic memory, suggesting that ADAD may have a slightly different pattern of decline than sporadic AD. Episodic memory composite performance in non-carriers, asymptomatic (CDR 0) mutation carriers, and symptomatic (CDR >0) mutation carriers plotted across estimated years from symptom onset. Note: For confidentiality purposes, specific years are not provided on the x-axis." @default.
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• W2537446510 date "2016-07-01" @default.
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• W2537446510 title "F5-02-01: COGNITIVE TRAJECTORIES IN DIAN: RELATIONSHIPS WITH SYMPTOM ONSET, MUTATION TYPES, AND CLINICAL STATUS" @default.
• W2537446510 doi "https://doi.org/10.1016/j.jalz.2016.06.687" @default.
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