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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.
Background: Increasing evidence suggests that functional impairment can be detected in older persons with mild cognitive impairment (MCI). This study explores the functional profiles and the clinical correlates of a population-based sample of Chinese older persons with MCI in Hong Kong.
Methods: A random sample of 765 Chinese elderly subjects without dementia was recruited, of which 389 were elderly normal controls (Clinical Dementia Rating = 0), and 376 had questionable dementia (CDR = 0.5). The latter were categorized into an MCI group (n = 291) and a very mild dementia (VMD) group (n = 85). Their functional performances were measured and compared with the normal controls (NC). Multiple regression analyses investigated the associations between functional scores (Disability Assessment in Dementia) and clinical correlates (cognitive test scores, neuropsychiatric symptoms and motor signs) in the NC subjects and cognitively impaired subjects.
Results: Subjects with MCI had intermediate functional performance between the NC and those with VMD. Regression analyses revealed that lower scores of cognitive tests (delayed recall and categorical verbal fluency tests), apathy, aberrant motor symptoms and parkinsonism features were associated with lower functional scores in clinically non-demented subjects. Functional scores had no correlation with age, education and medical illness burden.
Conclusion: Neuropsychiatric symptoms and parkinsonism features were associated with functional impairment in the clinically non-demented elderly in the community. Assessment of these should be incorporated in the evaluation of older persons for early cognitive impairment.
Introduction: In this report, the results of a household survey were used to examine the prevalence of very mild and mild dementia in Chinese older persons in Hong Kong.
Methods: The study adopted a two-phase design. At Phase 1, 6100 subjects were screened using the Cantonese version of the Mini-mental State Examination (MMSE) and a short memory inventory. At Phase 2, 2073 subjects were screened positive and 737 were evaluated by psychiatrists. Clinical Dementia Rating (CDR) and cognitive assessment were used for diagnosis of dementia. Very mild dementia (VMD) was defined as a global CDR of 0.5, with memory and non-memory subscale scores of 0.5 or more. Mild dementia was classified for subjects with a CDR of 1.
Results: The overall prevalence of VMD and mild dementia for persons aged 70 years or above was 8.5% (95%CI: 7.4–9.6) and 8.9% (95%CI: 7.8–10.0) respectively. Among subjects with clinical dementia, 84.6% had mild (CDR1) dementia. Logistic regression analyses revealed that older age, lower educational level and significant cerebrovascular risk factors were risk factors for dementia, while regular physical exercise was a protective factor for dementia.
Conclusions: A sizable proportion of community-living subjects suffered from milder forms of dementia. They represent a high risk for early intervention to reduce potential physical and psychiatric morbidity.
Background. The relative contribution of psychosocial and clinical risk factors to suicide among Chinese populations is an important issue. In Hong Kong, this issue requires vigorous examination in light of a 50% increase in suicide rate between 1997 and 2003.
Method. Using a case-control psychological autopsy method, 150 suicide deceased were compared with 150 living controls matched by age and gender. Semi-structured interviews were conducted with the next-of-kin of the subjects. Data were collected on a wide range of potential risk and protective factors, including demographic, life event, clinical and psychological variables. The relative contribution of these factors towards suicide was examined in a multiple logistic regression model.
Results. Six factors were found to significantly and independently contribute to suicide: unemployment, indebtedness, being single, social support, psychiatric illness, and history of past attempts.
Conclusions. Both psychosocial and clinical factors are important in suicides in Hong Kong. They seem to have mediated suicide risk independently. In addition, socio-economic adversities seem to have played a relatively important role in the increasing suicide rate in Hong Kong.
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