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Background: 'Cognitive reserve' (CR) refers to a model of active protection against cognitive decline conferred by the adaptability of one's cognitive processes. Research on life‐course accumulation of reserve and impact of factors like gender is limited. We examined long‐term effects of CR on episodic memory in two population‐based cohorts. Methods: Participants consists of two cohorts from the PATH Through Life project with 12 years (4 waves) of follow‐up, with had an average of 14.6 and 13.9 years of education. The mid‐life cohort (MA) was aged 40‐44 at baseline (mean age 42.6, 52.7% self‐reported female;47.3% male, 0% other gender, N = 2513) and the older cohort (OA) was aged 60‐64 at baseline (mean age 62.5, 48.1% female, 49.9% male, 0% other gender, N = 2403). A baseline composite CR measure included education, occupational complexity, and cognitive and social engagement measured by the RIASEC scales. Episodic memory (Immediate and delayed recall) was assessed with a 16‐word list. Multilevel models adjusting for baseline age, self‐reported gender, race, APOE and non‐English speaking background; evaluated the effect of both baseline and longitudinal change in CR on the longitudinal change in episodic memory. Results: On average, women performed better than men on the episodic memory tasks. Compared with participants in the top tertile of CR, those middle and lowest tertiles had larger decline in episodic memory in both MA and OA. Interactions with APOE were not significant, but among those with medium (model derived beta weights 95% CI: 0.35 (0.01‐0.69)) and high (0.48(0.07‐0.90)) CR, women showed less decline than men. Each component of CR (education, occupational complexity, and RIASEC) was protective against decline in immediate and delayed recall. Increase in RIASEC score over time was protective (MA (0.05, (0.04‐0.07); OA 0.13, (0.11‐0.16)) with a larger effect seen in OA. Conclusion: The current study demonstrated protective effects against cognitive decline for all types of CR measured in both middle and older‐age groups. Increases in CR over time were also protective. The benefits of CR were highest for older women who comprise the age and gender group at most risk of Alzheimer's disease, indicating the need for CR interventions. [ABSTRACT FROM AUTHOR]

Background: In a previous study, we demonstrated that the enzyme plasminogen activator inhibitor‐1 (PAI‐1), which inhibits plasmin synthesis in the central nervous system (CNS), is increased in the serum of patients with Alzheimer's disease (AD). In addition to reducing the accumulation of Ab, plasmin in the CNS regulates the synthesis of the trophic factor brain‐derived neurotrophic factor (BDNF) which appears to be altered in the brain of patients with AD. We investigated whether BDNF serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI‐1/BDNF ratio in these patient groups and correlated with cognitive scores as measured by Mini‐Mental State Examination (MMSE). Method: 40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and BDNF serum concentration were quantified by sandwich ELISAs. Comparisons among the experimental groups (AD dementia, aMCI patients, and cognitively healthy controls) on BDNF serum levels were performed using univariate analyses of variance (ANOVA). Pearson correlation coefficients were calculated to explore relationships between biochemical and clinical data. The level of statistical significance was set at p<0.05. Result: The results showed that BDNF serum levels are decreased in AD as compared to aMCI patients (p <.05). In addition, there was a positive correlation between PAI‐1 and BDNF serum levels (r =.190, p <.05). Furthermore, PAI‐1/BDNF ratio was significantly increased in AD patients as compared to aMCI (p <.001) and controls (p <.001). Lastly, PAI‐1/BDNF ratio negatively correlated with MMSE score (r = ‐.508, p <.001). Conclusion: These data suggest that in AD a reduction of plasmin caused by PAI‐1 may negatively affect the production of BDNF and promote disease progression. Our results also demonstrate that the PAI‐1/BDNF ratio is increased in AD patients compared with aMCI and controls. They also suggest that this ratio could be used as a marker of AD in a state of overt cognitive impairment, as supported by the strong negative correlation between PAI‐1/BDNF ratio and MMSE. [ABSTRACT FROM AUTHOR]

Background: Blood‐based biomarkers give the possibility of having a less invasive, more acceptable to patients, and cost‐ and time‐efficient screening tool. Therefore, blood‐based biomarkers represent an ideal addition to cerebrospinal fluid (CSF) and neuroimaging biomarkers. Standard examination of neurocognitive disorders, such as lumbar punction or brain PET scan, cannot be performed within general practice. Given the high prevalence of these diseases, alternatives such as blood‐based biomarkers would represent a significant advance. The aim of this study was to investigate whether levels of p‐tau 181 and neurofilament light chain (NfL) in serum and plasma can differentiate cognitively unimpaired (CU) elderly individuals from individuals in the stage of aMCI and dementia. Method: A total of 75 biomarker‐defined individuals from the Czech Brain Aging Study were recruited for the study, including the CU, individuals in the aMCI stage, and individuals in the stage of dementia syndrome with various etiology (AD, FTLD or LBD). Commercial ELISA kits were used for the assessment of standard biomarkers from CSF (Aß42, Aß40, pTau, tTau). Plasma and serum samples were analyzed using a Quanterix SR‐X analyzer with Simoa technology. Receiver operating characteristic analyses of the concentrations of p‐tau 181 and NfL in plasma and serum were performed using the R statistical software and GraphPad Prism. Result: Plasma NfL, AUC 0.9861 (95% CI, 0.9439 to 1.000), and serum NfL with AUC 0.9583 (95% CI, 0.8774 to 1.000) differentiated aMCI and dementia from CU with high predictive accuracy. The results were significant for plasma p‐tau 181 too with AUC 0.7869 (95% CI, 0.6474 to 0.9265), along with serum p‐tau 181 with AUC 0.7623 (95% CI, 0.6292 to 0.8954). Conclusion: Plasma and serum p‐tau 181 and NfL may be potentially useful and cost‐effective biomarkers for differentiating cognitively unimpaired elderly individuals from those at aMCI and dementia stages in general health care settings. [ABSTRACT FROM AUTHOR]