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Background: Long‐term forgetting (LTF) over days or weeks may be a sensitive early marker of Alzheimer's disease (AD), useful for preclinical AD trials. We examined associations between LTF and markers of brain pathology in individuals from the world's largest kindred with autosomal dominant AD due to the Presenilin‐1 (PSEN1) E280A mutation. Methods: A total of 14 cognitively unimpaired PSEN1 mutation carriers (mean age: 35.9 years) and 16 matched non‐carriers (mean age: 32.8 years) from the Colombia‐Boston Biomarker Study of autosomal dominant AD were included. Participants underwent amyloid (11‐C Pittsburgh compound B) and tau (Flortaucipir) PET imaging, and memory tasks (NEUROPSI word list, stories and semi‐complex figure). We examined performance on learning and delayed recall after a 20‐min, 1‐day and 7‐day interval. LTF was calculated for the three tasks as the proportion of material retained at 20 min that was recalled 7 days later. Mann‐Whitney tests were conducted to compare memory performance and LTF between PSEN1 mutation carriers and non‐carriers. Spearman's correlations were used to examine the association between LTF and brain pathology markers of amyloid burden and regional tau (entorhinal and inferior temporal cortices). Fisher's exact tests were used to compare correlation coefficients between groups. Results: Learning did not differ between carriers and non‐carriers. Compared to non‐carriers, carriers had lower 20‐min recall in all three tasks (p<0.05), and lower 1‐day and 7‐day recall of word list and stories. There were no group differences in word list, stories or figure LTF. Further, no group differences were observed in the association of amyloid burden and LTF on any of the tasks. Lower word list LTF was associated with greater entorhinal burden among carriers, and the strength of this association was significantly different between carriers and non‐carriers (p = 0.046; carriers: r = 0.73, p = 0.003; non‐carriers: r = 0.43, p = 0.094). Conclusions: Our preliminary findings show that, while rates of LTF over 7 days did not differ between PSEN1 carriers and non‐carriers, carriers had lower verbal memory recall over 1 and 7 days. Further, LTF was associated with early tau accumulation, suggesting that longer recall intervals may be more sensitive to detect subtle memory changes in cognitively unimpaired individuals at risk for AD. [ABSTRACT FROM AUTHOR]

Background: The identification of cognitive tests sensitive to subtle changes in the preclinical stage of Alzheimer's disease (AD) is of upmost importance to early detection of the disease, and to optimizing AD clinical trial recruitment. We used a delayed matching‐to‐sample (DMS) paradigm to study working memory for semantic relatedness in young adult carriers and non‐carriers of an autosomal dominant AD (ADAD) mutation from the Colombian kindred. Methods: 35 cognitively‐unimpaired Presenilin1 (PSEN1) E280A mutation carriers and 26 non‐carrier family members took the "Memory for Semantically‐Related Objects" test (MESERO), a computerized DMS working memory test for semantically‐related (and unrelated objects) developed by our group. The MESERO shows an equal number of either 4 or 6 objects that are semantically‐related or unrelated and records accuracy out of 80 points total (40 semantically‐related trials; 40 unrelated trials), as well as reaction time in milliseconds. Participants also completed the Mini‐Mental State Exam (MMSE). MESERO behavioral responses between groups were evaluated with the Mann‐Whitney test; age, MMSE scores, and education were compared with independent samples t‐tests. Results: Non‐carriers were significantly older (M = 36.7 years, SD = 6.5) and had slightly, but significantly higher MMSE scores (M = 28.8, SD = 6.5) than the carriers (age: M = 30.5, SD = 5.3; t = 3.92, p<.001; MMSE: M = 28.1, SD = 1.2; p<.001). The groups did not differ on education (∼mean of 11 years for both; t = 0.29, p =.39). On the MESERO total score, mutation carriers had significantly lower performance (mean = 70.8, SD = 6.5) relative to non‐carriers (mean = 73.5, SD = 5.7; U = 312, p =.04). The PSEN1 E280A carriers, in particular, performed worse on the semantically‐related trials (mean = 33.9, SD = 4.2) relative to non‐carriers (mean = 35.8, SD = 2.9; U = 312.5, p =.04), but not on unrelated trials (U = 357, p =.19). The carriers performed worse than non‐carriers on trials with 4‐items (mean = 35.5, SD = 4.2 vs. mean = 37.3, SD = 3.2) (U = 300.5, p =.02), but not with 6‐items in the study phase (U = 366.5, p =.19). Conclusion: A brief computerized working memory task for semantically‐related objects was able to distinguish cognitively unimpaired mutation carriers from non‐carriers from a Colombian kindred with autosomal dominant Alzheimer's disease, approximately 14 years before the median age of mild cognitive impairment onset in this cohort. Working memory for semantic relatedness warrants further study as a potential marker of preclinical AD. [ABSTRACT FROM AUTHOR]

AbstractObjective: Reports of financial exploitation have steadily increased among older adults. Few studies have examined neuropsychological profiles for individuals vulnerable to financial exploitation, and existing studies have focused on susceptibility to scams, one specific type of financial exploitation. The current study therefore examines whether a general measure of financial exploitation vulnerability is associated with neuropsychological performance in a community sample. Methods: A sample (n = 116) of adults aged 50 or older without dementia completed a laboratory visit that measures physical and psychological functioning and a neuropsychological assessment, the Uniform Data Set-3 (UDS-3) and California Verbal Learning Test-II. Results: After covarying for demographics, current medical problems, financial literacy, and a global cognition screen, financial exploitation vulnerability was negatively associated with scores on the Multilingual Naming Test, Craft Story Recall and Delayed Recall, California Verbal Learning Test-II Delayed Recall and Recognition Discriminability, Phonemic Fluency, and Trails B. Financial exploitation vulnerability was not associated with performance on Digit Span, Semantic Fluency, Benson Complex Figure Recall, or Trails A. Conclusions: Among older adults without dementia, individuals at higher risk for financial exploitation demonstrated worse verbal memory, confrontation naming, phonemic fluency, and set-shifting. These tests are generally sensitive to Default Mode Network functioning and Alzheimer’s Disease neuropathology. Longitudinal studies in more impaired samples are warranted to further corroborate and elucidate these relationships. [ABSTRACT FROM AUTHOR]