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Background: Life expectancy is on the rise, accompanied by an increased prevalence of cognitive impairment and Alzheimer's disease. Despite this global trend, our understanding of the neural mechanisms underlying cognitive changes in the oldest‐old (>80 years old) population remains limited. Unraveling these mechanisms may provide valuable insights and therapeutic interventions for individuals grappling with cognitive impairments in older age. Increased hippocampal volume has been associated with better cognitive function and its sparing in late life has been linked to better cognitive and functional outcomes. In this study, we examined hippocampal volume and cognitive performance in a group of the oldest‐old individuals from Colombia. Methods: 13 participants (9 women, 4 men), with an average age of 94.8 (6.24) years were included in this study. Cognitive performance was measured using the Mini‐Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Total. Functional impairment was assessed using the Functional Assessment Scale Test (FAST). Structural MRI scans were conducted at the Hospital Pablo Tobon Uribe in Colombia and processed with FreeSurfer (v7.2). Right and left hippocampal volumes were averaged. Linear regression models were used to investigate the relationship between hippocampal volume and cognitive performance. Results: 7 participants were cognitively‐unimpaired (FAST = 1), 3 endorsed subjective complaints (FAST = 2), and 3 met criteria for dementia (FAST ≥3). Participants had a mean hippocampal volume of 2,990 (459 mm³), mean MMSE score of 21.2 (6.15), and mean Memory Score of 10.5 (4.52). Regression models revealed higher hippocampal volume was significantly associated with better memory scores after adjusting for FAST impairment, age, sex, and intracranial volume (p = 0.012). The relationship between higher hippocampal volume and MMSE scores, controlling for the same variables, approached significance (p = 0.06). Conclusions: Our preliminary findings suggest a positive association between hippocampal volume, a marker of neurodegeneration, and cognitive performance in a cohort of the oldest‐old individuals from Colombia. This study is ongoing and future research, incorporating a larger sample size and additional biomarkers, is needed to validate these results, as well as to further our understanding of the relationship between neural structure in late life and cognition. [ABSTRACT FROM AUTHOR]

Background: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant ( APOE3 Ch ). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent., Methods: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants., Results: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18 F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18 F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant., Conclusions: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.)., (Copyright © 2024 Massachusetts Medical Society.)