Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

AbstractIntroductionThis meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.MethodMEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d.ResultsA total of 38 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.DiscussionCN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition

Learning deficit in cognitively normal apoe ε4 carriers with low β-amyloid

Introduction: In cognitively normal (CN) adults, increased rates of amyloid beta (Aβ) accumulation can be detected in low Aβ (Aβ–) apolipoprotein E (APOE) ε4 carriers. We aimed to determine the effect of ε4 on the ability to benefit from experience (ie, learn) in Aβ–CNs. Methods: Aβ– CNs(n= 333) underwent episodic memory assessments every 18 months for 108 months. A subset (n = 48) completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT) over 6 days. Results: Aβ– ε4 carriers showed significantly lower rates of improvement on episodic memory over 108 months compared to non-carriers (d = 0.3). Rates of learning on the ORCA-LLT were significantly slower in Aβ– ε4 carriers compared to non-carriers (d = 1.2). Discussion: In Aβ– CNs,ε4 is associated with a reduced ability to benefit from experience. This manifested as reduced practice effects (small to moderate in magnitude) over 108 months on the episodic memory composite, and a learning deficit (large in magnitude) over 6 days on the ORCA-LLT. Alzheimer’s disease (AD)–related cognitive abnormalities can manifest before preclinical AD thresholds

Association of deficits in short-term learning and Aβ and hippocampal volume in cognitively normal adults

© 2020 American Academy of Neurology. OBJECTIVE: To determine the extent to which deficits in learning over 6 days are associated with β-amyloid-positive (Aβ+) and hippocampal volume in cognitively normal (CN) adults. METHODS: Eighty CN older adults who had undergone PET neuroimaging to determine Aβ status (n = 42 Aβ- and 38 Aβ+), MRI to determine hippocampal and ventricular volume, and repeated assessment of memory were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Participants completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT), which required they learn associations between 50 Chinese characters and their English language equivalents over 6 days. ORCA-LLT assessments were supervised on the first day and were completed remotely online for all remaining days. RESULTS: Learning curves in the Aβ+ CN participants were significantly worse than those in matched Aβ- CN participants, with the magnitude of this difference very large (d [95% confidence interval (CI)] 2.22 [1.64-2.75], p \u3c 0.001), and greater than differences between these groups for memory decline since their enrollment in AIBL (d [95% CI] 0.52 [0.07-0.96], p = 0.021), or memory impairment at their most recent visit. In Aβ+ CN adults, slower rates of learning were associated with smaller hippocampal and larger ventricular volumes. CONCLUSIONS: These results suggest that in CN participants, Aβ+ is associated more strongly with a deficit in learning than any aspect of memory dysfunction. Slower rates of learning in Aβ+ CN participants were associated with hippocampal volume loss. Considered together, these data suggest that the primary cognitive consequence of Aβ+ is a failure to benefit from experience when exposed to novel stimuli, even over very short periods