Shea Andrews | bioRxiv Science

bioRxiv2016

Association of AKAP6 and MIR2113 with cognitive performance in a population based sample of older adults

Genetic factors make a substantial contribution to inter-individual variability in cognitive function. A recent meta-analysis of genome-wide association studies identified two loci, AKAP6 and MIR2113 that are associated with general cognitive function. Here, we extend this previous research by investigating the association of MIR2113 and AKAP6 with baseline and longitudinal nonlinear change across a broad spectrum of cognitive domains in community-based cohort of 1,570 older adults without dementia. Two SNPs, MIR211-rs10457441 and AKAP6-rs17522122 were genotyped in 1,570 non-demented older Australians of European ancestry, who were examined up to 4 times over 12 years. Linear mixed effects models were used to examine the association between AKAP6 and MIR2113 with cognitive performance in episodic memory, working memory, vocabulary, perceptual speed and reaction time at baseline and with linear and quadratic rates of change. AKAP6-rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain. MIR2113-rs10457441*T was associated with accelerated decline in episodic memory. No other associations with baseline cognitive performance or with linear or quadratic rate or cognitive changes was observed for this SNP. These results confirm the previous finding that, AKAP6 is associated with performance across multiple cognitive domains at baseline but not with cognitive decline, while MIR2113 primarily affects the rate at which memory declines over time.

Genetics↗

bioRxiv2016

ANU-ADRI and not Genetic Risk score predicts MCI in a cohort of older adults followed for 12 years

AbstractO_ST_ABSINTRODUCTIONC_ST_ABSWe evaluated a risk score comprising lifestyle, medical and demographic factors (ANU-ADRI), and a genetic risk score (GRS) as predictors of Mild Cognitive Impairment (MCI).\n\nMETHODSANU-ADRI risk scores were computed for the baseline assessment of 2,078 participants from the PATH project. Participants were assessed for clinically diagnosed MCI/Dementia and psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models estimated the odds of transitioning from cognitively normal (CN) to MCI/Dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS.\n\nRESULTSHigher ANU-ADRI score predicted transitioning from CN to either MCI/Dementia and MCI-TB (Hazard ratio [HR] = 1.06, 95% CI:1.04-1.09; HR = 1.06, 95% CI: 1.03-1.09), and a reduced likelihood of cognitive recovery from MCITB to CN (HR = 0.69, 95% CI: 0.49-0.98). GRS was not associated with transition to MCI/Dementia, or MCI-TB.\n\nDISCUSSIONThe ANU-ADRI may be used for population-level risk assessment and screening.\n\nResearch in ContextO_ST_ABSSystematic ReviewC_ST_ABSThe authors reviewed the literature using online databases e.g. (PubMed). We consulted mild cognitive impairment (MCI) and Alzheimers disease (AD) research detailing the use of risk factors for predicting progression from MCI and AD; and the appropriate statistical models for modelling transitions between cognitive states. These publications are appropriately cited.\n\nInterpretationIn the general population, the ANU-ADRI comprising lifestyle, medical and demographic factors is predictive of progression from normal cognition to MCI/Dementia whereas a Genetic Risk Score comprising the main Alzheimers risk genes is not predictive.\n\nFuture DirectionsFurther evaluation of the ANU-ADRI as a predictor of specific MCI and dementia subtypes is required. The ANU-ADRI may be used to identify individuals indicated for risk reduction intervention and to assist clinical management and cognitive health promotion. Genetic risk scores contribute to understanding dementia etiology but apart from APOE are unlikely to be useful in screening or prevention trials.

Genetics↗