Search

Background: Aging is often characterized by progressive cognitive decline in memory and executive function. Yet, some adults aged 80 years or older, are "Super‐Agers" that exhibit cognitive performance akin to younger adults. It is unknown if there are adults in mid‐life with similar superior cognitive performance ("positive‐aging") versus cognitive decline over time, and if there are blood biomarkers that can distinguish between these groups. Method: Among 1303 participants in UK Biobank, latent growth curve models classified participants into different cognitive groups based on longitudinal Fluid Intelligence (FI) scores over 7‐9 years. Random Forest (RF) classification was then used to predict cognitive trajectory types using longitudinal predictors including demographic, vascular, bioenergetic, and immune factors. Feature ranking importance and performance metrics of the model were reported. Result: Despite model complexity, we achieved a precision of 77% when determining who would be in the "positive‐aging" group. Among the top fifteen features, an equal number were related to either vascular health or cellular bioenergetics but not demographics like age, sex, or socioeconomic status (see figure). Conclusion: Our results suggest that optimal cognitive aging may not be driven by age per se, but biological factors that may be amenable to lifestyle or pharmacological changes. [ABSTRACT FROM AUTHOR]

Background: To determine if 3‐year changes in serum insulin resistance (IR) were related to changes in brain volume and glucose uptake, cognition, and CSF biomarkers in cognitively unimpaired and impaired older adults. Method: Alzheimer's Disease Neuroimaging Initiative data was downloaded for 275 aged adults (55‐89 years). Participants had longitudinal T1‐ and T2‐weighted volume scans, fluorodeoxyglucose (FDG) scans, CSF β‐amyloid (Aβ) and tau species, and cognitive performance over baseline and months 6, 12, 18, 24, and 36. Growth curve modeling in R regressed IR against these outcomes, by itself and with clinical diagnosis as a moderator. Cognitively unimpaired (CU) adults were used as a reference group to determine potential effects in pathological aging. Result: In AD and/or Mild Cognitive Impairment progressors to AD (MCI‐P), higher IR over time was related to progressive atrophy in medial temporal frontoinsular areas. Similarly, decline was seen in global cognition and both memory and executive function. HOMA1‐IR associations were partially mediated by p‐tau‐181. Among clinical diagnosis groups, higher IR was significantly related to amyloid, p‐tau‐181, and total tau 181 among AD patients but not MCI or unimpaired groups. Conclusion: These findings suggest that in older adults who develop AD or had AD at baseline, higher IR over time is related to brain atrophy and consequent cognitive decline, perhaps as a function of amyloid or tau deposition. [ABSTRACT FROM AUTHOR]

Background: 58‐79% of late‐onset Alzheimer's disease (AD) is due to genetic heritability. The epsilon 4 (ε4) variant of Apolipoprotein E (APOE) is the strongest genetic risk factor for AD, yet only accounts for 20% of AD heritability. In addition, the APOE ε2 or ε3 variants appear to have either a protective or neutral effect on AD risk respectively. Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is next to APOE and may modulate different APOE variant effects, such as with the Single Nucleotide Polymorphism (SNP) at rs2075650. Thus, we explored main and interaction effects of TOMM40 and APOE on longitudinal measures of executive function and memory. Method: 10,347 adults (40‐70y) in the UK Biobank were genotyped for APOE and TOMM40 '650. Executive function and memory were tested at baseline and twice over a period of 6‐10 years. Main effects within APOE haplotypes and TOMM40 SNP genotypes (A,G) were analyzed, as well as interactions between these genetic markers. Result: Having the TOMM40 '650 G risk variant was related to better baseline cognitive scores regardless of APOE haplotype (ps <.05), but a greater decline over time in APOE4 carriers (ps <.05) The effects of the APOE haplotype were strongly modulated by sex. Men vs. women had less protective or more detrimental effects based on APOE2 or APOE4 haplotype respectively. Conclusion: The data suggests that TOMM40 modulates APOE, regardless of its haplotype. Future studies should stratify APOE by haplotype to re‐test our findings. In addition, more research needs to be done on the effect of having what we term a "mixed" APOE haplotype (carrying a copy of both the protective and risk gene variants). [ABSTRACT FROM AUTHOR]

Introduction: Aging is often associated with cognitive decline. Understanding neural factors that distinguish adults in midlife with superior cognitive abilities (Positive-Agers) may offer insight into how the aging brain achieves resilience. The goals of this study are to (1) introduce an optimal labeling mechanism to distinguish between Positive-Agers and Cognitive Decliners, and (2) identify Positive-Agers using neuronal functional connectivity networks data and demographics., Methods: In this study, principal component analysis initially created latent cognitive trajectories groups. A hybrid algorithm of machine learning and optimization was then designed to predict latent groups using neuronal functional connectivity networks derived from resting state functional magnetic resonance imaging. Specifically, the Optimal Labeling with Bayesian Optimization (OLBO) algorithm used an unsupervised approach, iterating a logistic regression function with Bayesian posterior updating. This study encompassed 6369 adults from the UK Biobank cohort., Results: OLBO outperformed baseline models, achieving an area under the curve of 88% when distinguishing between Positive-Agers and cognitive decliners., Discussion: OLBO may be a novel algorithm that distinguishes cognitive trajectories with a high degree of accuracy in cognitively unimpaired adults., Highlights: Design an algorithm to distinguish between a Positive-Ager and a Cognitive-Decliner.Introduce a mathematical definition for cognitive classes based on cognitive tests.Accurate Positive-Ager identification using rsfMRI and demographic data (AUC = 0.88).Posterior default mode network has the highest impact on Positive-Aging odds ratio., Competing Interests: This study uses UK Biobank data. UK Biobank has ethical approval from the North West Multi‐centre Research Ethics Committee (MREC) (https://www.ukbiobank.ac.uk/learn‐more‐about‐uk‐biobank/about‐us/ethics). Written informed consent was obtained from all participants., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Glucose hypometabolism and tau formation are key features of Alzheimer's disease (AD). Less is known about the relationship between fasting glucose and regional tau accumulation., Methods: Cerebrospinal fluid (CSF) glucose was linearly regressed on regional tau (flortaucipir) among 169 Alzheimer's Disease Neuroimaging Initiative (ADNI3) participants. Flortaucipir uptake was examined by Braak stages and regions of interest (ROIs). Interactions were explored between CSF glucose and AD risk factors including regional amyloid beta (Aβ), sex, Apolipoprotein E ε4 ( APOE ε4) status, AD parental family history (AD FH), and cognitive impairment (CI)., Results: Interactions found higher CSF glucose tracked less tau in ROIs or Braak stages I/II (women, APOE ε4+, regional Aβ), III/IV (AD FH+, regional Aβ), and V/VI (AD FH+). CI drove Braak III-VI associations., Discussion: Among women and APOE ε4 carriers, higher CSF glucose tracked less early-stage tau. Higher CSF glucose may reflect compensation against tau spreading in CI, Aβ+, or AD FH+., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)