Rate Of Cognitive Change Research Articles

Education and cognitive reserve in old age.

To assess the contribution of education to cognitive reserve. Analyses are based on older participants in a longitudinal clinical-pathologic cohort study who had annual cognitive testing (n = 2,899) and subgroups that developed incident dementia (n = 696), died, and underwent a neuropathologic examination from which 10 neurodegenerative and cerebrovascular markers were derived (n = 752), or both (n = 405). Cognitive test scores were converted to a standard scale and averaged to yield composite measures of cognition. Participants had a mean of 16.3 years of education (SD = 3.7, range 0-30). In all participants, education was associated with initial level of global cognition but not rate of cognitive change. In those who developed dementia, rate of global cognitive decline accelerated a mean of 1.8 years before the diagnosis, but education was not related to the onset or rate of accelerated decline. In the deceased, rate of global cognitive decline accelerated a mean of 3.4 years before death, but higher educational attainment was related to earlier (not later) onset of accelerated decline and unrelated to rate of acceleration. Higher education was associated with lower likelihood of gross and microscopic cerebral infarcts but not with other neuropathologic markers. Education was not related to global cognitive change not attributable to neuropathologic burden and did not decrease the association of higher neuropathologic burden with more rapid cognitive decline. The results suggest that the contribution of education to cognitive reserve is limited to its association with level of cognitive function before old age.

Childhood socioeconomic status predicts cognitive outcomes across adulthood following traumatic brain injury

ObjectiveTo examine the association between childhood socioeconomic status (SES) and the level and rate of change in intelligence scores throughout adulthood following traumatic brain injury (TBI). MethodsIn this longitudinal study we tested 186 patients with TBI and 54 healthy controls from the Vietnam Head Injury Study. Childhood SES was determined for each participant based on parental educational attainment and occupational prestige. General intelligence was initially assessed pre-injury upon induction into the military, and again 15, 35 and 40+ years post-injury. We examined whether childhood SES, total brain volume loss and lesion laterality can predict post-injury intelligence scores and the rate of change in those scores between study phases. ResultsFor both participants with and without TBI, childhood SES accounted for a significant portion of the variance in intelligence scores pre-injury and in all three post-injury evaluations, however, it was not associated with the rate of cognitive change. Lastly, childhood SES predicted cognitive outcome among patients with left hemisphere damage better than it did for right hemisphere damage patients. ConclusionsThese findings provide the first evidence indicating the persistent effects of childhood SES on intelligence scores later in adulthood following a TBI. Childhood SES should be considered when predicting and assessing cognitive recovery following TBI, even when the injury occurred in adulthood.

Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging

The link between exposure to general anaesthesia and surgery (exposure) and cognitive decline in older adults is debated. We hypothesised that it is associated with cognitive decline. We analysed the longitudinal cognitive function trajectory in a cohort of older adults. Models assessed the rate of change in cognition over time, and its association with exposure to anaesthesia and surgery. Analyses assessed whether exposure in the 20 yr before enrolment is associated with cognitive decline when compared with those unexposed, and whether post-enrolment exposure is associated with a change in cognition in those unexposed before enrolment. We included 1819 subjects with median (25th and 75th percentiles) follow-up of 5.1 (2.7-7.6) yr and 4 (3-6) cognitive assessments. Exposure in the previous 20 yr was associated with a greater negative slope compared with not exposed (slope: -0.077 vs -0.059; difference: -0.018; 95% confidence interval: -0.032, -0.003; P=0.015). Post-enrolment exposure in those previously unexposed was associated with a change in slope after exposure (slope: -0.100 vs -0.059 for post-exposure vs pre-exposure, respectively; difference: -0.041; 95% confidence interval: -0.074, -0.008; P=0.016). Cognitive impairment could be attributed to declines in memory and attention/executive cognitive domains. In older adults, exposure to general anaesthesia and surgery was associated with a subtle decline in cognitive z-scores. For an individual with no prior exposure and with exposure after enrolment, the decline in cognitive function over a 5 yr period after the exposure would be 0.2 standard deviations more than the expected decline as a result of ageing. This small cognitive decline could be meaningful for individuals with already low baseline cognition.

Prospective associations between pulse pressure and cognitive performance in Chinese middle-aged and older population across a 5-year study period

BackgroundSubstantial evidence indicates that the relationship between blood pressure (BP) measures and cognitive functioning is inconsistent, complex, and age-related. Pulse pressure (PP), which can not only reflect arterial stiffness and but also represent the chronic effects of hypertension other than BP itself, has been considered as a better predictor of cognitive impairment. However, evidence on the association of cognitive function with PP has not been investigated extensively. We examined this relationship in a longitudinal study based on the latent growth model (LGM).MethodsThis study was based on a nationally representative sample of Chinese middle-aged and older participants from the China Health and Retirement Longitudinal Study (CHARLS), a prospective observational study conducted from 2011 to 2016. Cognitive performance was assessed on the basis of three measures of cognition. The PP was calculated as the difference of the average values of three systolic and diastolic BP readings. A series of potential confounders were collected in this research. The LGM was used to examine the effects of PP on cognitive performance at three time points. To test the independent effects of PP on the initial level and the subsequent development of cognition, unconditional and conditional models were compared sequentially.ResultsAfter excluding respondents with missing key variables, we ultimately included 9750 participants in the analysis. Cognitive performance scores and PP showed significant differences across time. After adjustment for the confounders, the standardized coefficients of PP in the LGM indicated negative effects on cognitive performance in elderly Chinese participants at wave 2 and wave 3 (P < 0.01). The initial level of PP in the unconditional model was negatively associated with the initial level (β = − 0.25) and the slope (β = − 0.16) of cognition, whereas these effects were attenuated and the association between intercept of PP and slope of cognition became nonsignificant after controlling for the confounders.ConclusionsThe implications of these results demonstrate that a higher PP lowers the cognitive performance of middle-aged and elderly persons independent of a comprehensive set of covariates, but it is not a contributor to the rate of change in cognition.

Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration. Higher CR scores were associated with better cognitive performance but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI before symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline.

Childhood social class and cognitive aging in the Swedish Adoption/Twin Study of Aging

In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the Swedish socioeconomic index. Cognitive ability included a general factor and the four domains of verbal, fluid, memory, and perceptual speed. Latent growth curve models of the longitudinal data tested whether level and change in cognitive performance differed as a function of childhood social class. Between-within twin-pair analyses were performed on twins reared apart to assess familial confounding. Childhood social class was significantly associated with mean-level cognitive performance at age 65 y, but not with rate of cognitive change. The association decreased in magnitude but remained significant after adjustments for level of education and the degree to which the rearing family was supportive toward education. A between-pair effect of childhood social class was significant in all cognitive domains, whereas within-pair estimates were attenuated, indicating genetic confounding. Thus, childhood social class is important for cognitive performance in adulthood on a population level, but the association is largely attributable to genetic influences.

Change of Cognitive Function in U.S. Chinese Older Adults: A Population-Based Study.

This study aims to assess cognitive change in a 2-year period among U.S. Chinese older adults and examine sociodemographic characteristics associated with the change. Data were from the Population Study of Chinese Elderly (PINE) in which 2,713 participants (aged 60 and older) received in-home interviews at both the baseline and 2-year follow-up. A battery of cognitive tests that assessed episodic memory, working memory, perceptual speed, and overall cognitive status were administered in both times. A composite global cognition was constructed using all tests. Mixed-effect regression was conducted. Older age was associated with worse baseline cognition (ie, in all cognitive abilities) and faster decline in global cognition, episodic memory, and perceptual speed-rates of decline increased by .006, .004, and .009 standard score units, respectively, for each year older. More education was associated with better baseline cognition, but each year of additional schooling increased rates of decline in global cognition and episodic memory by .004 and .012 standard score units, respectively. Men performed better than women in most cognitive abilities at baseline but had faster rates of decline in working memory. Higher income was associated with better cognition at baseline and reduced rates of decline in working memory. Findings suggest differences in the rates of cognitive change by age, sex, education, and income. Those in advancing age are vulnerable to cognitive decline. The effects of education and sex on baseline performance versus change suggest a role for life experiences in cognition.

Comparing individual differences in inconsistency and plasticity as predictors of cognitive function in older adults

ABSTRACTIntroduction: Recent theorizing differentiates key constraints on cognition, including one’s current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. Method: Participants included 304 adults (aged 64 to 92 years: M = 74.02, SD = 5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time (RT) measures (choice RT and one-back choice RT), baseline measures of RT inconsistency (intraindividual standard deviation, ISD, across trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed and were then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6-year) rates of cognitive change. Results: Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. Conclusions: These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults.

MMSE and MoCA in Parkinson's disease and dementia with Lewy bodies: a multicenter 1-year follow-up study.

The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to test cognitive impairment in Lewy body disease (LBD), but there is no consensus on which is best suited to assess cognition in clinical practice and most sensitive to cognitive decline. Retrospective cohort study of 265 LBD patients [Parkinson's disease (PD) without dementia (PDnD, N = 197), PD with dementia (PDD, N = 40), and dementia with Lewy bodies (DLB, N = 28)] from an international consortium who completed both the MMSE and MoCA at baseline and 1-year follow-up (N = 153). Percentage of relative standard deviation (RSD%) at baseline was the measure of inter-individual variance, and estimation of change (Cohen's d) over time was calculated. RSD% for the MoCA (21 %) was greater than for the MMSE (13 %) (p = 0.03) in the whole group. This difference was significant only in PDnD (11 vs. 5 %, p < 0.01), but not in PDD (30 vs. 19 %, p = 0.37) or DLB (15 vs. 14 %, p = 0.78). In contrast, the 1-year estimation of change did not differ between the two tests in any of the groups (Cohen's effect <0.20 in each group). MMSE and MoCA are equal in measuring the rate of cognitive changes over time in LBD. However, in PDnD, the MoCA is a better measure of cognitive status as it lacks both ceiling and floor effects.

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

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. To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. 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 Prevención con Dieta Mediterránea 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. 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). 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. 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 < .05) decreased from baseline in controls. In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. isrctn.org Identifier: ISRCTN35739639.

The nature and rate of cognitive maturation from late childhood to adulthood.

To better understand the nature and rate of cognitive change across adolescence, the Cogstate Brief Battery (CBB) was utilized to assess psychomotor function, attention, working memory, and visual learning in individuals aged 10–18 years old. Since all CBB tasks have equivalent perceptual, motor, and linguistic demands as well as being appropriate for both children and adults, this approach allowed direct across-age comparison of multiple cognitive domains. Exponential decreases in reaction time and linear increases in accuracy were observed across adolescent development in a cross-sectional sample of 38,778 individuals and confirmed in a 5788 individual longitudinal sample with 1-year repeat assessments. These results have important implications for the repeated assessment of cognition during development where expected maturational changes in cognition must be accounted for during cognitive testing.

Degree of abnormality is associated with rate of change in measures of beta-amyloid, glucose metabolism and cognition in an autopsy-verified Alzheimer’s disease case

The degree of abnormality and rate of change in cognitive functions, positron emission tomography Pittsburg compound B (PET PIB), and fluorodeoxyglucose (FDG) measures were studied for 8 years in an autopsy-confirmed Alzheimer’s disease (AD) patient, who died 61 years old (Mini-Mental State Examination (MMSE) score 7). At first encounter with medical care, the patient was very mildly demented (MMSE score 27). She had four cognitive assessments and two examinations with PET PIB and FDG in 23 bilateral brain regions. The onset of cognitive decline was retrospectively estimated to have started in the early forties. The degree of impairment was inversely related to the rate of decline. A similar relationship was seen between the rate of change and the level of abnormality in both PIB and FDG. To conclude, rate of change in cognition, PIB, and FDG was associated with the degree of abnormality.

Education Desegregation and Cognitive Change in African American Older Adults.

The present study examined the relationship between desegregated schooling and cognitive change in a sample of 420 community-dwelling African American elders (mean age = 68.6; SD = 9.1). Participants were recruited for the Baltimore Study of Black Aging - Patterns of Cognitive Aging. Cognitive measures from six domains of function were administered at baseline and follow-up 33 months later. Repeated measures multivariate analysis of covariance was conducted; the between subjects factors were schooling type and age cohort, and the within subjects factor was time. Analyses controlled for age, years of education, and sex, and follow-up univariate analyses were used to determine which individual cognitive scores drove the multivariate effects. There were significant multivariate within-group, between-group, and interaction effects (p < .05). Univariate analyses indicated that the desegregated schooling group scored significantly better on Language and Perceptual Speed (p < .01), and the youngest age cohort (50- to 59-year-olds) performed better on measures of Perceptual Speed. There were no significant univariate interactions between schooling group or age cohort and cognitive change over time. Overall, these findings suggest a slight advantage of desegregated schooling for cognitive performance, but no advantage of desegregated schooling on the rate of cognitive change over time in this sample.

Components of late-life exercise and cognitive function: an 8-year longitudinal study.

The preventive effect of late-life physical exercise on cognitive deterioration has been reported in many cohort studies. However, the effect of exercise, independent of other cognitively demanding and social activities, is equivocal and little is known about the relative contributions of frequency, intensity, and duration of exercise. This study aimed to examine the relationships of exercise and its underlying components with cognitive function and rate of cognitive change over an 8-year period in a nationally representative sample of older Taiwanese. Data from the 1999, 2003, and 2007 phases of the nationwide longitudinal survey were used. Data from a fixed cohort of 1,268 participants aged 70 years or older in 1999 with 8 years of follow-up were analyzed. Cognitive function was assessed using the Short Portable Mental Status Questionnaire. Self-reported frequency, intensity, and duration of exercise were collected. A generalized estimating equation with multivariate adjustment for sociodemographic variables, cognitive and social leisure activities, lifestyle behaviors, and health status was calculated. Participants who were physically active during leisure time had better subsequent cognitive function (incident rate ratios [IRR] = 0.63; 95 % CI, 0.54-0.75) and a slower rate of cognitive decline (p = 0.01). Among the components of exercise, only duration emerged as a predictor of cognitive function (p = 0.01). Older adults engaging in exercise for at least 30 min or more per session are likely to reduce the risk of subsequent cognitive decline. This research supports the case for physical exercise programs for older adults in order to help prevent loss of cognitive function.

APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease.

Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4+], ɛ4 non-carrier[ɛ4−]) and brain-derived neurotrophic factor (BDNFVal/Val, BDNFMet) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ− or Aβ+. Relative to Aβ−ɛ4−, Aβ+ɛ4+ individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40–1.22), while Aβ+ɛ4− individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ−ɛ4− and Aβ−ɛ4+ groups. Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4−/BDNFVal/Val participants (d=0.90–1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ− and Aβ+ ɛ4− groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials.

How does it STAC up? Revisiting the scaffolding theory of aging and cognition.

“The Scaffolding Theory of Aging and Cognition (STAC)”, proposed in 2009, is a conceptual model of cognitive aging that integrated evidence from structural and functional neuroimaging to explain how the combined effects of adverse and compensatory neural processes produce varying levels of cognitive function. The model made clear and testable predictions about how different brain variables, both structural and functional, were related to cognitive function, focusing on the core construct of compensatory scaffolding. The present paper provides a revised model that integrates new evidence about the aging brain that has emerged since STAC was published 5 years ago. Unlike the original STAC model, STAC-r incorporates life-course factors that serve to enhance or deplete neural resources, thereby influencing the developmental course of brain structure and function, as well as cognition, over time. Life-course factors also influence compensatory processes that are engaged to meet cognitive challenge, and to ameliorate the adverse effects of structural and functional decline. The revised model is discussed in relation to recent lifespan and longitudinal data as well as emerging evidence about the effects of training interventions. STAC-r goes beyond the previous model by combining a life-span approach with a life-course approach to understand and predict cognitive status and rate of cognitive change over time.

Spotlight on the October 22 Issue

The authors assessed the relationship between prerandomization red blood cell docosahexaenoic acid + eicosapentaenoic acid levels and cognitive function in 2,157 cognitively normal women. After adjustment for demographic, clinical, and behavioral characteristics, there were no cognitive differences at the time of the first annual cognitive battery or in the rate of cognitive change. See p. 1484 A quantitative lipidomic analysis was conducted on 524 longitudinal CSF samples. Subjects included HIV-infected individuals with longitudinal clinical and cognitive test data and cognitively normal HIV-negative healthy controls. HIV infection and combination antiretroviral therapy (cART) were …

Omega-3 fatty acids and domain-specific cognitive aging

To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time. We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.

Substantial effects of apolipoprotein E ε4 on memory decline in very old age: longitudinal findings from a population-based sample

We examined associations between the apolipoprotein E (APOE) ε4 allele and levels of performance and rates of change in cognition in late life taking incident dementia into account. The sample consisted of 482 nondemented individuals, aged 80 years and older at baseline, drawn from the OCTO twin study. A battery of 10 cognitive tests was administered at 5 occasions with measurements intervals of 2 years. We fitted hierarchical linear models with time specified as time to death and controlled for baseline age, sex, education, stroke, cardiovascular disease, hypertension, diabetes, and incident dementia. The ε4 allele was significantly associated with lower levels of performance or steeper rate of decline in all 7 memory tests. Largest effect sizes were found in tests of delayed recall and recognition memory. The effects of the APOE ε4 allele were, however, reduced to a nonsignificant level in all tests except 1 after accounting for incident dementia. The findings support the notion that the APOE ε4 allele is associated with substantial memory decline in very old age, but as expected, the effect is largely related to incident dementia.

Modulation of beta-amyloid-related cognitive decline by brain-derived neurotrophic factor Val66Met polymorphism in preclinical Alzheimer's disease

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has previously been implicated in Alzheimer's disease (AD)-related cognitive impairment. We aimed to determine whether BDNF Val66Met moderates A β amyloid-related cognitive decline, reduction in hippocampal volume, and A β amyloid accumulation in healthy older adults. Healthy older adults (n=165) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study underwent positron emission tomography (PET) neuroimaging for Aβ amyloid using Pittsburgh Compound B (PiB), BDNF genotyping, and cognitive assessment at baseline, 18- and 36-months. Linear mixed models determined rates of change in cognition, hippocampal volume and A β amyloid accumulation over 36 months. In healthy older adults with high Aβ amyloid, Met carriers showed significant and moderate-to-large decline in episodic memory, executive function, and language, and greater reductions in hippocampal volume over 36 months compared to Val/Val homozygotes. BDNF Val66Met was unrelated to rates of change in cognition or hippocampal volume in participants with low Aβ amyloid. BDNF Val66Met was not associated with levels of Aβ amyloid in participants with high or low Aβ amyloid levels at baseline. Similarly, BDNF Val66Met was not associated with rates of Aβ amyloid accumulation in participants with high or low Aβ amyloid levels at baseline. BDNF Val66Met moderated the association between high A β amyloid and cognitive decline and hippocampal atrophy in healthy older adults. High A β amyloid levels coupled with Met carriage may be useful prognostic markers of accelerated cognitive decline and hippocampal degeneration in individuals in the preclinical stage of AD.