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Episodic memory performance in a multi-ethnic longitudinal study of 13,037 elderly.

ABSTRACT: Age-related changes in memory are not uniform, even in the absence of dementia. Characterization of non-disease associated cognitive changes is crucial to gain a more complete understanding of brain aging. Episodic memory was investigated in 13,037 ethnically diverse elderly (ages 72 to 85 years) with two to 15 years of follow-up, and with known dementia status, age, sex, education, and APOE genotypes. Adjusted trajectories of episodic memory performance over time were estimated using Latent Class Mixed Models. Analysis was conducted using two samples at baseline evaluation: i) non-cognitively impaired individuals, and ii) all individuals regardless of dementia status. We calculated the age-specific annual incidence rates of dementia in the non-demented elderly (n = 10,220). Two major episodic memory trajectories were estimated: 1) Stable-consisting of individuals exhibiting a constant or improved memory function, and 2) Decliner-consisting of individuals whose memory function declined. The majority of the study participants maintain their memory performance over time. Compared to those with Stable trajectory, individuals characterized as Decliners were more likely to have non-white ethnic background, fewer years of education, a higher frequency of ε4 allele at APOE gene and five times more likely to develop dementia. The steepest decline in episodic memory was observed in Caribbean-Hispanics compared to non-Hispanic whites (p = 4.3 x 10(-15)). The highest incident rates of dementia were observed in the oldest age group, among those of Caribbean-Hispanics ancestry and among Decliners who exhibited rates five times higher than those with Stable trajectories (11 per 100 person-years versus 3 per 100 person-years. Age, education, ethnic background and APOE genotype influence the maintenance of episodic memory. Declining memory is one of the strongest predictors of incident dementia.

SUBMITTER: Lee S

PROVIDER: S-EPMC6248922 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IMPORTANCE:There are genetic influences on memory ability as we age, but no specific genes have been identified. OBJECTIVE:To use a cognitive endophenotype, exceptional episodic memory (EEM) performance, derived from nondemented offspring from the Long Life Family Study (LLFS) to identify genetic variants that may be responsible for the high cognitive performance of LLFS participants and further replicate these variants using an additional 4006 nondemented individuals from 4 independent elderly cohorts. DESIGN, SETTING, AND PARTICIPANTS:A total of 467 LLFS participants from 18 families with 2 or more offspring that exhibited exceptional memory performance were used for genome-wide linkage analysis. Adjusted multivariate linear analyses in the 40-megabase region encompassing the linkage peak were conducted using 4 independent replication data sets that included 4006 nondemented elderly individuals. Results of the individual replication cohorts were combined by meta-analysis. MAIN OUTCOME MEASURE:Episodic memory scores computed as the mean of the 2 standardized measures of Logical Memory IA and IIA. RESULTS:Heritability estimates indicated a significant genetic component for EEM (h2 = 0.21; SE = 0.09). Genome-wide linkage analysis revealed that EEM was linked to the 6q24 region (maximum logarithm of odds score, 3.64). Association analysis in LLFS families identified single-nucleotide polymorphisms (SNPs) nominally associated with EEM in the 40-megabase window encompassing the linkage peak. Replication in one cohort identified a set of 26 SNPs associated with episodic memory (P ? .05). Meta-analysis of the 26 SNPs using the 4 independent replication cohorts found SNPs rs9321334 and rs6902875 to be nominally significantly associated with episodic memory (P = .009 and P = .013, respectively). With meta-analysis restricted to individuals lacking an APOE ?4 allele, SNP rs6902875 became statistically significant (meta-analysis, P = 6.7 × 10-5). Haplotype analysis incorporating the 2 SNPs flanking rs6902875 (rs9321334 and rs4897574) revealed that the A-A-C haplotype was significantly associated with episodic memory performance (P = 2.4 × 10-5). This genomic region harbors monooxygenase dopamine ?-hydroxylase-like 1 gene (MOXD1), implicated in the biosynthesis of norepinephrine, which is prominently involved in cognitive functions. CONCLUSIONS AND RELEVANCE:The results provide strong evidence for potential candidate genes related to EEM on 6q24. Identifying the genes will help in understanding the biological basis of memory performance and allow interventions for enhancement of cognitive function.

Project description:Healthy ageing is accompanied by cognitive decline that affects episodic memory processes in particular. Studies showed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may counteract this cognitive deterioration by increasing excitability and inducing neuroplasticity in the targeted cortical region. While stimulation gains are more consistent in initial low performers, relying solely on behavioural measures to predict treatment benefits does not suffice for a reliable implementation of this method as a therapeutic option. Hence, an exploration of the underlying neurophysiological mechanisms regarding the differential stimulation effect is warranted. Glutamatergic metabolites (Glx) and ?-aminobutyric acid (GABA) are involved in learning and memory processes and can be influenced with tDCS; wherefore, they present themselves as potential biomarkers for tDCS-induced behavioural gains, which are affiliated with neuroplasticity processes. In the present randomized, double-blind, sham-controlled, crossover study, 33 healthy young and 22 elderly participants received anodal tDCS to their left DLPFC during the encoding phase of a verbal episodic memory task. Using MEGA-PRESS edited magnetic resonance spectroscopy (MRS), Glx and GABA levels were measured in the left DLPFC before and after the stimulation period. Further, we tested whether baseline performance and neurotransmitter levels predicted subsequent gains. No beneficial group effects of tDCS emerged in either verbal retrieval performances or neurotransmitter concentrations. Moreover, baseline performance levels did not predict stimulation-induced cognitive gains, nor did Glx or GABA levels. Nevertheless, exploratory analyses suggested a predictive value of the Glx?:?GABA ratio, with lower ratios at baseline indicating greater tDCS-related gains in delayed recall performance. This highlights the importance of further studies investigating neurophysiological mechanisms underlying previously observed stimulation-induced cognitive benefits and their respective interindividual heterogeneity.

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Episodic memory performance in a multi-ethnic longitudinal study of 13,037 elderly.

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