Cognitive decline

About: Cognitive decline is a research topic. Over the lifetime, 29308 publications have been published within this topic receiving 1174689 citations.

MIND diet associated with reduced incidence of Alzheimer's disease

Abstract: Introduction In a previous study, higher concordance to the MIND diet, a hybrid Mediterranean-Dietary Approaches to Stop Hypertension diet, was associated with slower cognitive decline. In this study we related these three dietary patterns to incident Alzheimer's disease (AD). Methods We investigated the diet-AD relations in a prospective study of 923 participants, ages 58 to 98 years, followed on average 4.5 years. Diet was assessed by a semiquantitative food frequency questionnaire. Results In adjusted proportional hazards models, the second (hazards ratio or HR = 0.65, 95% confidence interval or CI 0.44, 0.98) and highest tertiles (HR = 0.47, 95% CI 0.26, 0.76) of MIND diet scores had lower rates of AD versus tertile 1, whereas only the third tertiles of the DASH (HR = 0.61, 95% CI 0.38, 0.97) and Mediterranean (HR = 0.46, 95% CI 0.26, 0.79) diets were associated with lower AD rates. Discussion High adherence to all three diets may reduce AD risk. Moderate adherence to the MIND diet may also decrease AD risk.

Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline.

Abstract: Objective: Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline. Methods: A total of 1,352 participants without dementia from the prospective Framingham Offspring Cohort Study were examined. Multivariable linear and logistic regressions were implemented to study the association of midlife vascular risk factor exposure with longitudinal change in white matter hyperintensity volume (WMHV), total brain volume (TBV), temporal horn volume, logical memory delayed recall, visual reproductions delayed-recall (VR-d), and Trail-Making Test B-A (TrB-A) performance a decade later. Results: Hypertension in midlife was associated with accelerated WMHV progression ( p p = 0.012). Midlife diabetes and smoking were associated with a more rapid increase in temporal horn volume, a surrogate marker of accelerated hippocampal atrophy ( p = 0.017 and p = 0.008, respectively). Midlife smoking also predicted a more marked decrease in total brain volume ( p = 0.025) and increased risk of extensive change in WMHV (odds ratio = 1.58 [95%confidence interval 1.07–2.33], p = 0.021). Obesity in midlife was associated with an increased risk of being in the top quartile of change in executive function (1.39 [1.02–1.88], p = 0.035) and increasing waist-to-hip ratio was associated with marked decline in TBV (10.81 [1.44–81.01], p = 0.021). Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function. Conclusions: Midlife hypertension, diabetes, smoking, and obesity were associated with an increased rate of progression of vascular brain injury, global and hippocampal atrophy, and decline in executive function a decade later.

Quantification of biological aging in young adults.

Abstract: Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial

Abstract: Importance Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. Objective To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. Design, Setting, and Participants Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevencion con Dieta Mediterranea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. Interventions Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). Main Outcomes and Measures Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. Results Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049) and Color Trail Test part 2 ( P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (−0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (−0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and −0.17 (−0.32 to −0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (−0.25 to 0.31), and −0.33 (−0.57 to −0.09). Changes from baseline of the global cognition composite were 0.05 (−0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, −0.05 (−0.27 to 0.18) for the Mediterranean diet plus nuts, and −0.38 (−0.57 to −0.18) for the control diet. All cognitive composites significantly ( P Conclusions and Relevance In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. Trial Registration isrctn.org Identifier:ISRCTN35739639

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Abstract: Vascular contributions to dementia and Alzheimer's disease are increasingly recognized1-6. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction7, including the early clinical stages of Alzheimer's disease5,8-10. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease11-14, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes15-19, which maintain BBB integrity20-22. It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the e3/e4 or e4/e4 alleles) are distinguished from those without APOE4 (e3/e3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-β or tau pathology measured in cerebrospinal fluid or by positron emission tomography23. High baseline levels of the BBB pericyte injury biomarker soluble PDGFRβ7,8 in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-β and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway19 in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer's disease pathology, and might be a therapeutic target in APOE4 carriers.