50 research outputs found

    Editorial: Insights in Neurocognitive Aging and Behavior: 2021

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    In recent years, exceptional scientific achievements have led to major advancements in the fast-growing field of neurocognitive aging and behavior. In this inaugural collection, Insights in Neurocognitive Aging and Behavior: 2021, we sought to highlight the latest advancements and challenges for the current state of knowledge and future directions in aging neuroscience in the neurocognitive arena. Here we outline the contributions and implications for future research of the 15 papers in this topic collection across four important research areas: (1) novel approaches to identifying and tracking brain aging and impending cognitive decline; (2) neurocognitive markers of risks for Alzheimerā€™s disease (AD) and its progression; (3) lifestyle contributions to cognitive aging and AD; and (4) the status and future of neurocognitive and brain aging theory

    Identifying Changepoints in Biomarkers During the Preclinical Phase of Alzheimerā€™s Disease

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    Objective: Several models have been proposed for the evolution of Alzheimerā€™s disease (AD) biomarkers. The aim of this study was to identify changepoints in a range of biomarkers during the preclinical phase of AD.Methods: We examined nine measures based on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and cognitive testing, obtained from 306 cognitively normal individuals, a subset of whom subsequently progressed to the symptomatic phase of AD. A changepoint model was used to determine which of the measures had a significant change in slope in relation to clinical symptom onset.Results: All nine measures had significant changepoints, all of which preceded symptom onset, however, the timing of these changepoints varied considerably. A single measure, CSF t-tau, had an early changepoint (34 years prior to symptom onset). A group of measures, including the remaining CSF measures (CSF Abeta and phosphorylated tau) and all cognitive tests had changepoints 10ā€“15 years prior to symptom onset. A second group is formed by medial temporal lobe shape composite measures, with a 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset).Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance

    Alzheimerā€™s disease genetic risk and cognitive reserve in relationship to long-term cognitive trajectories among cognitively normal individuals

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    Background: Both Alzheimerā€™s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition. Methods: Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-Īµ2 and APOE-Īµ4 vs. APOE-Īµ3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function. Results: In mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-Īµ4 genotype and AD-PRS that included the APOE region (AD-PRSAPOE) were associated with declines in all cognitive domains, whereas AD-PRS that excluded the APOE region (AD-PRSw/oAPOE) was associated with declines in executive function and global cognition, but not memory. There were significant 3-way CR index score Ɨ APOE-Īµ4 Ɨ time interactions for the global (p = 0.04, effect size = 0.16) and memory scores (p = 0.01, effect size = 0.22), indicating the negative effect of APOE-Īµ4 genotype on global and episodic memory score change was attenuated among individuals with higher CR index scores. In contrast, levels of CR did not attenuate APOE-Īµ4-related declines in executive function or declines associated with higher AD-PRS. APOE-Īµ2 genotype was unrelated to cognition. Conclusions: These results suggest that APOE-Īµ4 and non-APOE-Īµ4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-Īµ4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-Īµ4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics

    Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance

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    Several concepts, which in the aggregate get might be used to account for ā€œresilienceā€ against ageā€ and diseaseā€related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language
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