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The amyloid beta (Aβ) 42/40 ratio has been widely studied as a biomarker in Alzheimer's disease (AD); however, other Aβ peptides could also represent relevant biomarkers. We measured levels of Aβ38/40/42 in plasma samples from cognitively-unimpaired older adults and determined the relationships between Aβ levels and amyloid positron-emission-tomography (PET) and performance on a learning and memory task. We found that all Aβ peptides individually and the Aβ42/40 ratio, but not the Aβ42/38 ratio, were significantly correlated with brain amyloid (Aβ-PET). Multiple linear modeling, adjusting for age, sex, education, APOE4 and Aβ-PET showed significant associations between the Aβ42/38 ratio and memory. Further, associations between the Aβ42/38 ratio and learning scores were stronger in males and in Aβ-PET-negative individuals. In contrast, no significant associations were detected between the Aβ42/40 ratio and any learning measure. These studies implicate the Aβ42/38 ratio as a biomarker to assess early memory deficits and underscore the utility of the Aβ38 fragment as an important biomarker in the AD field., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A blood-based biomarker of Alzheimer's disease (AD) progression could be instrumental in targeting asymptomatic individuals for treatment early in the disease process. Given the direct connection between sphingomyelins (SM), ceramides, and apoptosis, these lipids may be indicators of neurodegeneration and AD progression. Baseline serum SM and ceramides from 100 women enrolled in a longitudinal population-based study were examined as predictors of cognitive impairment. Participants were followed up to six visits over 9 years. Baseline lipids, in tertiles, were examined in relation to cross-sectional and incident impairment (<1.5 S.D. below standard norms) on HVLT-immediate and -delayed memory recall and Trails A and B. SM and ceramides varied in relation to the timing of HVLT-delayed impairment: low levels were associated with cross-sectional impairment; high levels predicted incident impairment in asymptomatic individuals. Lipids were not associated with loss-to-follow-up. Results suggest serum SM and ceramides vary according to the timing of the onset of memory impairment and may be good pre-clinical predictors, or biomarkers, of memory impairment: a deficit observed early in AD pathogenesis.

Objectives: To investigate the associations between circulating cytokines and specific neuropsychological domains of cognitive functioning (memory, processing speed and motor function) and general cognitive function (MMSE) in healthy elderly individuals., Methods: In a cross-sectional study of 369 community dwelling elderly subjects, we examined the relationship between serum IL-1beta, sIL-4R, IL-6, IL-8, IL-10, IL-12 and TNF-alpha concentrations and cognitive performance using an extensive standardized and validated cognitive test battery assessing memory, word fluency, perceptual/cognitive speed, attention and executive functioning, and motor speed., Results: Multivariate analysis adjusted for various confounders and Bonferroni correction for multiple comparisons demonstrated that increased serum concentrations of IL-8 were associated with poor performance in the memory and speed domains and in motor function. No significant associations were found between the remaining cytokines and domains of cognitive functioning. Global cognitive functioning, as measured with MMSE, was not associated with any cytokine., Conclusions: This study suggests an association between circulating IL-8 concentrations and cognitive dysfunction in the elderly. An interaction between this cytokine and glial cells may help explain the pathophysiological mechanisms leading to cognitive impairment in our study group.

The origin and clinical significance of subjective memory complaints among middle aged and older individuals is not well understood. Associations with objective memory impairments, personality traits or mood disturbances have been reported. Elevated cortisol levels occur in aging and depression and causal links to cognitive or emotional problems have been suggested. The goal of this study was to investigate the associations between basal and feedback indices of cortisol regulation and subjective memory impairment in a sample of healthy middle aged and older subjects (mean age 61.8 years) with (n=27) and without (n=19) subjective memory complaints. Participants with memory complaints had both higher basal cortisol levels and higher cortisol levels after dexamethasone. There was a significant group by gender interaction for basal cortisol levels, where women without memory complaints showed significantly lower cortisol levels, whereas no such difference was found for the men. All effects were not due to slight differences in depression scores. Differences in personality traits or in stress susceptibility might underlie the present findings. Future studies of memory complaints should take a comprehensive approach including relevant endocrine parameters.