Aim It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD‐related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid‐beta (Aβ) burden, AD‐signature regional neurodegeneration, and white matter hyperintensities (WMH) in non‐demented middle‐ and old‐aged adults. Methods A total of 397 non‐demented participants underwent comprehensive clinical and neuropsychological assessments, 11C‐labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five‐Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. Results Neither neuroticism nor conscientiousness was associated with cerebral Aβ deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD‐signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD‐signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aβ deposition or WMH were not. Conclusion The present findings suggest that amyloid‐independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD.

INTRODUCTIONUsing nationwide cohort data, we aimed to elucidate whether baseline obesity altered the relationship between loss in body mass index (BMI) or waist circumference (WC) and risk of dementia.METHODSAmong 9689 participants whose BMIs and WCs were repeatedly measured over 1 year, 1:1 propensity score matching was conducted between participants with and without obesity (n = 2976 per group, mean age 70.9). For each group, we explored the association between loss in BMI, or WC, and incidence of dementia during an approximately 4‐year follow‐up period.RESULTSBMI loss was associated with an increased risk of all‐cause dementia and Alzheimer's disease in participants without obesity; however, this association was absent in participants with obesity. WC loss was associated with decreased Alzheimer's disease risk only in participants with obesity.DISCUSSIONOnly unfavorable loss (loss from non‐obese state) in BMI, not WC, can be a metabolic biomarker of prodromal dementia.

Background Although previous studies have reported associations of diabetes mellitus (DM) with cognitive impairment or dementia, the exact pathophysiological links underlying the associations remain incompletely understood. In this context, we aimed to investigate the associations of DM or glycated hemoglobin (HbA1c) with in vivo Alzheimer’s disease (AD) pathologies such as cerebral beta‐amyloid protein (Aβ) deposition and tau deposition. Method Total 136 participants (71 cognitively normal, 31 mild cognitive impairment, and 34 AD dementia) from the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study, were included for this analysis. All participants underwent comprehensive clinical and neuropsychological assessment, 11C labelled Pittsburgh Compound B (PiB) positron emission tomography (PET), 11F AV‐1451 PET, magnetic resonance imaging, apolipoprotein E genotyping, and HbA1c measurement. Result Neither the presence of DM nor HbA1c level was associated with global Aβ deposition after controlling for age, sex, education, vascular risk score (except DM), apolipoprotein e4 positivity, and clinical diagnosis. In contrast, higher HbA1c was significantly associated with lower AD‐signature region tau deposition and the presence of DM showed a trend level association with decreased tau deposition. Additionally, we found significant Aβ deposition x HbA1c (or the presence of DM) interaction effect on tau deposition. While higher Aβ deposition was significantly related to increased tau deposition in lower HbA1c (or DM negative) subgroup, there was no such relationship between Aβ and tau deposition in higher HbA1c (or DM positive) one. Sensitivity analyses including only cognitively normal individuals also showed similar results. Conclusion Our results indicate that DM or higher blood glucose may not contribute to cognitive impairment or dementia via AD‐specific pathologies, especially amyloid deposition. Therefore, other non‐AD pathophysiological contributions including vascular pathologies should be considered. Although being very cautious, high blood glucose may relate to delayed brain tau deposition.