Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

Default mode network (DMN) is vulnerable to the effects of APOE genotype. Given the reduced brain volumes and APOE ε 4-related brain changes in elderly carriers, it is less known that whether these changes would influence the functional connectivity and to what extent. This study aimed to examine the functional connectivity within DMN, and its diagnostic value with age-related morphometric alterations considered.

Whole brain and seed-based resting-state functional connectivity (RSFC) analysis were conducted in cognitively normal APOE ε 4 carriers and matched non-carriers (N=38). The absolute values of mean correlation coefficients (z-values) were used as a measure of functional connectivity strength (FCS) between DMN subregions, which were also used to estimate their diagnostic value by receiver-operating characteristic (ROC) curves.

APOE ε 4 carriers demonstrated decreased interhemispheric FCS, particularly between right hippocampal formation (R.HF) and left inferior parietal lobular (L.IPL) (t=3.487, p<0.001). ROC analysis showed that the FCS of R.HF and L.IPL could differentiate APOE ε 4 carriers from healthy counterparts (AUC value=0.734, p=0.025). Moreover, after adjusting the impact of morphometry, the differentiated value of FCS of R.HF and L.IPL was markedly improved (AUC value=0.828, p=0.002).

Our findings suggest that APOE ε 4 allele affects the functional connectivity within posterior DMN, particularly the atrophy-corrected interhemispheric FCS before the clinical expression of neurodegenerative disease.

Intra-individual variability (IIV) and the change of attentional functions have been reported to be susceptible to both healthy ageing and pathological ageing. The current study aimed to evaluate the IIV of attention and the age-related effect on alerting, orienting, and executive control in cognitively healthy older adults.

We evaluated 145 Chinese older adults (age range of 65–80 years, mean age of 72.41 years) with a comprehensive neuropsychological battery and the Attention network test (ANT). A two-step strategy of analytical methods was used: Firstly, the IIV of older adults was evaluated by the intraindividual coefficient of variation of reaction time (ICV-RT). The correlation between ICV-RT and age was used to evaluate the necessity of subgrouping. Further, the comparisons of ANT performance among three age groups were performed with processing speed adjusted.

Person's correlation revealed significant positive correlations between age and IIV (r = 0.185, p = 0.032), age and executive control (r = 0.253, p = 0.003). Furthermore, one-way ANOVA comparisons among three age groups revealed a significant age-related disturbance on executive control (F = 4.55, p = 0.01), in which oldest group (group with age >75 years) showed less efficient executive control than young-old (group with age 65–70 years) (Conventional score, p = 0.012; Ratio score, p = 0.020).

Advancing age has an effect on both IIV and executive attention in cognitively healthy older adults, suggesting that the disturbance of executive attention is a sensitive indicator to reflect healthy ageing. Its significance to predict further deterioration should be carefully evaluated with prospective studies.