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© 2019 Elsevier Inc. The longevity gene Klotho (KL), specifically the functional KL-VS variant, has previously been associated with cognition and rates of cognitive decline. This study aimed to determine whether KL-VS associations with cognition were observable in preclinical Alzheimer's disease (AD). The study also aimed to determine whether there was a combined influence of KL-VS, neocortical amyloid-ß (Aß) burden, and carriage of the apolipoprotein E (APOE) e4 allele on cognitive decline. This study involved 581 Aß-imaged, cognitively normal older adults, enrolled in the Australian Imaging, Biomarkers and Lifestyle Study of Aging. Linear mixed effects models revealed no significant associations between KL-VS and cognitive decline independently or in combination with Aß burden and APOE e4 genotype. Overall, previous associations reported between KL-VS and cognitive decline are not observed at the preclinical stages of AD. Furthermore, the results do not support the hypothesis that KL-VS has a modifying effect on Aß burden and APOE e4–driven cognitive decline in preclinical AD.

Background It is common for older adults to experience decline in some cognitive functions with increasing age. Importantly, a subset, usually referred to as super-agers (SA; Rogalski, et al., 2013, J Cog Neurosc, 25: 29-36) live to an old age whilst continuing to maintain cognitive function at levels similar to demographically-matched peers at least 20-30 years their junior. The current study reports trajectories of change in cortical thickness on a well-defined group of SAs vs. typical agers (TA) followed longitudinally over six years in the Australian Imaging, Biomarkers & Lifestyle Study (AIBL) (Ellis et al., 2009, Int Psychogeriat, 2: 672-87). Methods Super-Agers were defined as individuals aged 60+ who scored in the normative range for individuals aged 30 – 44 on the CVLT-II, a test of verbal episodic memory, at baseline and two consecutive time-points 18 months apart. SAs additionally must have performed in the unimpaired range in all other cognitive domains, as compared to same-aged peers. Typical agers must have scored within the normal range on all cognitive measures compared with same-aged peers. This report describes data from 21 SAs and 24 TAs. The TAs were chosen from a larger group matched on age, education and gender to the SA group. All participants completed brain magnetic resonance imaging every 18 months for six years. We conducted multiple linear mixed models analyses to assess the association between preservation of cortical thickness in SAs and TAs. Results From 34 regions of interest identified as potentially differentiating SAs from TAs from previous neuroimaging studies, our results were consistent in finding greater cortical thinning amongst TAs in 20 of these regions (p-values ranging between ≤ .000 and .047), with an additional five regions at trend level (p-values ranging between ≥ .05 and .073). Using false discovery rates, we found significantly preserved thickness in three regions not previously reported including left superior parie

Objective To examine how β-amyloid (Aβ), APOE and BDNF genotypes, and cortisol relate to depressive and anxiety symptoms in cognitively normal older women and men. Methods Cross-sectional data were analyzed from 423 older adults from the Australian Imaging Biomarkers and Lifestyle study. Analyses of covariance evaluated associations between Aβ, APOE and BDNF genotype, and cortisol in relation to severity of depressive and anxiety symptoms. Results Among Aβ+ older adults, APOE ε4 carriage was associated with greater severity of anxiety symptoms (d = 0.55); and in the full sample, APOE ε4 carriage was linked to greater severity of depressive (d = 0.26) and anxiety (d = 0.21) symptoms. Among Aβ+ women, ε4 carriers reported greater anxiety symptoms than non-ε4 carriers (d = 0.83), and female BDNF rs6265 Val66 Met allele carriers reported greater depressive symptoms (d = 0.29). Conclusion Sex moderated the relationship between Aβ, APOE genotype, and BDNF genotype in predicting severity of anxiety and depressive symptoms in cognitively normal older adults.