Development and validation of cognitive ageing risk score (CARS) for early detection of subtle cognitive deficits in older people.

BACKGROUND: Early cognitive deficits commonly seen in older people have not been well defined and managed in primary care. The objectives are (1) to develop and validate a new risk score to estimate the risk of dementia in Chinese older population; and (2) to evaluate the use of risk score in conjunction with cognitive screening in detecting early cognitive deficits in community older people. METHODS: A development cohort of 306 cognitive healthy older adults aged 60 or above were followed for 6 years. A CARS was constructed using the estimated coefficients of risk factors associated with dementia at follow up. Validation was carried out in another five-year cohort of 383 older adults. The usefulness of CARS in detecting early cognitive deficits was evaluated. RESULTS: Risk factors include older age, male gender, low level of education, poorly controlled diabetes, prolonged sleep latency, fewer mind body or light exercise, loneliness, and being apolipoprotein e4 carriers. A cutoff of CARS at -1.3 had a sensitivity of 83.9% and a specificity of 75.4% to predict dementia. The area under curve was 82.5% in the development cohort. Early cognitive deficits were characterized by impaired retention (p <.001, 95% CI 0.2-0.9) and attention (p =.012, 95% CI 0.1-0.8). CONCLUSION: The CARS can be used as a standard risk assessment of dementia or in conjunction with a computerized cognitive screening to evaluate a full cognitive profile for detecting early cognitive deficits. The result put forward the integration of risk algorithm into smart healthcare system to provide personalized lifestyle interventions.

The association between satisfaction with life and anxiety symptoms among Chinese elderly: a moderated mediation analysis.

BACKGROUND: Previous studies have suggested that certain personal psychological variables (e.g., life satisfaction and cognitive function) and physical variables (e.g., body mass index [BMI]) are significantly associated with individuals' anxiety symptoms. However, relevant research on elderly is lagging and no studies have yet investigated the combined impact of these variables on anxiety. Thus, we conducted the present study to investigate the potential moderator role of BMI and the potential mediator role of cognitive function underlying the relationship between life satisfaction and anxiety symptoms in Chinese elderly based in Hong Kong. METHODS: Sixty-seven elderly aged 65 years old and above were recruited from the local elderly community centres in this pilot study. Each participant underwent a systematic evaluation using the Satisfaction with Life Scale (SWLS), Hong Kong Version of the Montreal Cognitive Assessment (HK-MoCA), and the Hamilton Anxiety Rating Scale (HAM-A) and were measured for their body weight and height. Regression analysis using the bootstrapping method was employed to test the hypothesized moderated mediation model. RESULTS: Our findings demonstrated the overall model accounted for 23.05% of the variance in scores of HAM-A (F (8, 57) = 2.134, p = 0.047) in Chinese elderly. There was a significant association between life satisfaction and anxiety symptoms (p = 0.031), indicating that individuals with higher life satisfaction were associated with less anxiety symptoms. Moreover, this relationship was positively moderated by BMI (b = 0.066, 95% CI [0.004, 0.128]), especially in Chinese elderly with BMI at a lower level (b = -0.571, 95% CI [-0.919, -0.224]) and an average level (b = -0.242, 95% CI [-0.460, -0.023]). No significant mediator role was detected for cognitive function (b = -0.006, 95% CI [-0.047, 0.044]) in our model. CONCLUSIONS: Our findings suggest that increased life satisfaction can reduce anxiety symptoms among Chinese elderly as their BMI decreases (when BMI ranged between "mean - 1SD" and "mean" of the population). The significant interaction between psychological and physical factors underlying anxiety symptoms found in this study, presents a promising opportunity for translation into multi-level psychological and physical interventions for the management of anxiety in ageing patients during clinical practice.

Diversity in verbal fluency performance and its associations with MRI-informed brain age matrices in normal ageing and neurocognitive disorders.

INTRODUCTION: Category verbal fluency test (CVFT) has been widely used to assess and monitor the cognitive capacities in epidemiological studies and clinical trials. Pronounced discrepancy in CVFT performance has been found in individuals with different cognitive statuses. This study aimed to combine the psychometric and morphometric approaches to decode the complex verbal fluency performance in senior adults with normal ageing and neurocognitive disorders. METHODS: This study adopted a two-stage cross-sectional design involving quantitative analyses of neuropsychological and neuroimaging data. In study I, capacity- and speed-based measures of CVFT were developed to evaluate the verbal fluency performance in normal ageing seniors (n = 261), those with mild cognitive impairment (n = 204), and those with dementia (n = 23) whose age range is from 65 to 85 years. In study II, structural magnetic resonance imaging-informed gray matter volume (GMV) and brain age matrices were calculated in a subsample (n = 52) from Study I through surface-based morphometry analysis. With age and gender as covariates, Pearson's correlation analysis was used to examine the associations of CVFT measures, GMV, and brain age matrices. RESULTS: Speed-based measures showed extensive and stronger associations with other cognitive functions than capacity-based measures. The component-specific CVFT measures showed shared and unique neural underpinnings with lateralized morphometric features. Moreover, the increased CVFT capacity was significantly correlated with younger brain age in mild neurocognitive disorder (NCD) patients. CONCLUSION: We found that the diversity of verbal fluency performance in normal ageing and NCD patients could be explained by a combination of memory, language, and executive abilities. The component-specific measures and related lateralized morphometric correlates also highlight the underlying theoretical meaning of verbal fluency performance and its clinical utility in detecting and tracing the cognitive trajectory in individuals with accelerated ageing.

The Role of Depressive Symptoms and Physical Activity Levels in Mediating the Association Between HIV Status and Neurocognitive Functions Among Individuals Aged at Least 50 Years in China: Cross-sectional Study.

BACKGROUND: Neurocognitive impairments are prevalent among older people in China. It is more problematic among older people living with HIV. OBJECTIVE: This study aims to compare neurocognitive performance between older people living with HIV and HIV-negative controls, and to explore whether the association between HIV status and neurocognitive performance was mediated by depressive symptoms and level of physical activity. METHODS: A cross-sectional study was conducted in Yongzhou, China. All people living with HIV aged ≥50 years listed in the registry were invited. Frequency matching was used to sample HIV-negative controls from the general population according to the distribution of age, sex, and years of formal education of older people living with HIV. A total of 315 older people living with HIV and 350 HIV-negative controls completed the face-to-face interview and comprehensive neuropsychological assessment of seven domains (learning, memory, working memory, verbal fluency, processing speed, executive function, and motor skills). RESULTS: As compared to HIV-negative controls, older people living with HIV performed worse in global score and all seven domains (P<.05). HIV infection was associated with higher depressive symptoms (P<.001) and lower level of physical activity (P<.001). Depressive symptoms and physical activity were negatively correlated (P<.001). Depressive symptoms and level of physical activity mediated the association between HIV status and global z-score and four domain z-scores of neurocognitive performance (learning, memory, verbal fluency, and processing speed). CONCLUSIONS: Change in mental health and physical activity after HIV infection may partially explain why older people living with HIV are more susceptible to neurocognitive impairment. Promoting mental health and physical activity are potential entry points to slow down the progress of neurocognitive impairment among older people living with HIV.

Is sleep quality a potential predictor of neurocognitive disorders? A 6-year follow-up study in Chinese older adults.

OBJECTIVE: To investigate the longitudinal association of sleep quality with incidence of neurocognitive disorders in 6 years. METHODS: This was a 6-year follow-up study of community-living older adults who scored a Clinical Dementia Rating (CDR) of 0 at baseline. Sleep quality was assessed by the self-rated Pittsburgh Sleep Quality Index (PSQI) questionnaire, where higher scores indicated poorer sleep quality, and a cutoff score of 5 or above was suggestive of sleep disorder. The study outcome was incident neurocognitive disorders in 6 years, as identified by a CDR of 0.5 or above. Poisson regression analysis was conducted to test if baseline sleep quality was independently associated with risk of incident neurocognitive disorders in 6 years. RESULTS: Of the 290 participants in this study, 166 (57.2%) developed neurocognitive disorders in 6 years. They had poorer sleep quality (mean [SD] total PSQI score: 6.2 [3.8] vs. 4.9 [3.2], p = 0.001) and higher prevalence of sleep disorder (100 [60.2%] vs. 56 [45.2%], p = 0.01) at baseline than those who remained free of neurocognitive disorder. After controlling for age, gender, education, and physical and psychiatric morbidities, the risk ratios (RRs) for incident neurocognitive disorders were 1.05 (95% confidence interval (CI) = 1.00-1.11, p < 0.05) for PSQI total score and 1.50 (95% CI = 1.05-2.14, p = 0.03) for sleep disorder at baseline. CONCLUSIONS: Sleep quality might predict the development of neurocognitive disorders. From a clinical perspective, enquiry of sleep quality and screening for sleep disorder should be promoted as part of the neurocognitive disorder risk assessment in older adults.

Information Communication Technology as Instrumental Activities of Daily Living for Aging-in-Place in Chinese Older Adults With and Without Cognitive Impairment: The Validation Study of Advanced Instrumental Activities of Daily Living Scale.

Background: The capability in applying information communication technology (ICT) is crucial to the functional independence of older peoples of community living nowadays. The proper assessment of individuals' capability of ICT application is the corner stone for the future development of telemedicine in our aging population. Methods: With the recruitment of 300 participants of different functional and social background in home-living, hostel-living, and care-and-attention home living; and through assessing the ability of individuals in instrumental activities of daily living and cognitive assessments, this study aimed at capturing the content validity and construct validity of the Advanced Instrumental Activities of Daily Living (AIADL scale). In addition, this study assess the ability of older peoples in applying ICT and how the functional and social background affects their independence in aging-in-place. Results: The AIADL scale showed good test-retest reliability and good-to-excellent internal consistency. To determine if items of the AIADL scale measure various aspects of community living, exploratory factor analysis revealed a two-factor structure with "home living and management" and "community living". Validity analysis with the known-groups method showed a high overall accuracy of prediction of individuals' capability of independent living in the community. Conclusions: The AIADL scale is a valid and reliable instrument to assess the ability of older adults in handling ICT as part of their instrumental activities in daily living. The scale can reflect capability of older peoples in applying ICT. This instrument can serve as a reference in measuring readiness of individuals in receiving telemedicine and their ability of aging-in-place.

Late-life longitudinal blood pressure trajectories as predictor of dementia.

While hypertension is widely recognized as a risk factor for dementia, few observational studies and clinical trials fully accounted for the effect of age on blood pressure (BP) changes prior to dementia onset. In this territory-wide population-based longitudinal study of 16,591 community-living dementia-free older adults, we followed their BP and cognitive status and tested if loss of longitudinal increase in BP in late life was associated with higher dementia risk in 6 years, with consideration of the confounding effects of hypertension, hypotension, BP variability, and other health problems and behaviours and, in the data analysis, exclusion of individuals who developed dementia within 3 years after baseline to minimize risk of reverse causality. Over 72,997 person-years of follow-up, 1429 participants developed dementia. We found that loss of longitudinal increase in systolic BP (defined as SBP increased by either < 10 mmHg or 10%) from baseline to Year 3 was independently associated with higher risk of incident dementia at Years 4 to 6 (adjusted OR 1.22, 95% CI 1.02-1.45, p = 0.03; adjusted OR 1.24, 95% CI 1.03-1.50, p = 0.02; respectively). Our findings suggest that late-life SBP trajectory changes might independently predict dementia onset and highlight the importance of including longitudinal BP monitoring in dementia risk assessment.

Mindfulness Awareness Is Associated With a Lower Risk of Anxiety and Depressive Symptoms in Older Adults With Neurocognitive Disorders.

Background: Apart from depressive disorders, there are great interests in adopting mindfulness based interventions (MBIs) for other mental health conditions. Depression and anxiety are common in people with neurocognitive disorders (NCD). The potential of MBIs as an adjuvant treatment in this cognitively at-risk group should be further explored. Objectives: The current study explored the association between depression and anxiety symptoms with dispositional mindfulness in older adults, and if same association stays in the context of cognitive impairment. Methods: The Hong Kong Mental Morbidity Survey for Older People (MMSOP) is an ongoing epidemiology study of the prevalence of neurocognitive and mental disorders in adults aged 60 years or over in Hong Kong. MMSOP evaluated cognitive function, psychiatric symptoms (Clinical Interview Schedule-revised, CIS-R), chronic physical disease burden, psychosocial support, and resilience factors, including dispositional mindfulness as measured by the Mindful Attention Awareness Scale (MAAS). We analyzed the impact of MAAS on CIS-R and potential moderation effects of mindfulness. Results: In March 2021, 1,218 community dwelling participants completed assessments. The mean age of the sample is 69.0 (SD 6.9) years. Eight hundred and two participants (65.7%) were not demented (CDR 0) and 391 (32%) and 25 (2%) were categorized as having mild NCD (CDR 0.5) and major NCD (CDR 1 or more), respectively. One hundred forty-three (11.7%) satisfied ICD-10 criteria for anxiety or depressive disorder as measured by CIS-R. Linear regression analysis showed that female gender, CIRS, and MAAS scores were significant factors associated with CIS-R scores. MAAS scores moderated and attenuated the impact CIRS on CIS-R (adjusted R 2 = 0.447, p < 0.001). MAAS scores remained as significant moderator for CIRS in patients with NCD (CDR ≥ 0.5) (adjusted R 2 = 0.33, p < 0.001). Conclusion: Interim findings of the MMSOP suggested that dispositional mindfulness is associated with lower level of mood symptoms in community dwelling older adults in Hong Kong. The interaction effects further suggested that high mindful awareness may reduce the adverse effects of chronic physical morbidity on mental health. The observation stayed in the participants with cognitive impairment. We should further explore MBIs as a non-pharmacological treatment for in older adults at-risk of physical morbidity and cognitive decline.

Knowledge of mental health symptoms and help seeking attitude in a population-based sample in Hong Kong.

BACKGROUND: Mental health symptoms can be subtle, resulting in delaying treatment. A prompt identification of mental signs and symptoms is important for preventing mental disorders in the public. This study examined whether local public have adequate knowledge to identify mental health symptoms and the need to get timely professional help. METHODS: The population-based telephone surveys were conducted in 2015 and 2018. It involved a random sample of 4033 respondents aged 12-75 years. Mental health knowledge and help seeking attitude were assessed using six vignettes depicting subtle and obvious symptoms of anxiety disorders, mixed anxiety and depressive disorders, and dementia. Logistic regression models were performed to examine association between mental health knowledge and help-seeking attitude. RESULTS: Individuals with poor knowledge in subtle symptoms were more likely to be males (t = - 5.0, p < .001), younger (F = 15.0, p < .001), have tertiary education (F = 15.0, p < .001), and employed (t = - 2.1, p = .037). The knowledge scores of subtle and obvious symptoms were 1.5 and 2.3 respectively. Binary logistic regression found that poor knowledge of subtle symptoms was associated with reluctance to professional help seeking. CONCLUSIONS: Poorly identified subtle mental health symptoms is a major barrier to early professional help in highly educated working males. Future research should explore specific interventions to increase knowledge and professional help seeking in this group.

Risk of incident dementia varies with different onset and courses of depression.

BACKGROUND: This study aims to examine if risk of dementia differs between adult- and late-onset depression. METHODS: 16,608 community-living dementia-free older adults were followed for 6 years to the outcome of incident dementia. Depression was diagnosed according to international diagnostic guidelines. Depression in adulthood or late life was categorized using age 65 as cutoff. Hazard ratio for dementia was estimated using Cox regression analysis. RESULTS: People with depression in adulthood only did not have higher dementia incidence, suggesting those in remission from adult-onset depression are not at greater risk of dementia. Conversely, having depression in both adulthood and late life was associated with higher dementia risk, and improvement in depression in late life was associated with lower risk, suggesting persistent or recurrent lifetime depression is a risk factor for dementia. Those with depression in late life only were not associated with higher dementia risk after controlling for the longitudinal changes in depressive symptoms, consistent with late-onset depression being a prodrome of dementia. LIMITATIONS: Reverse causation is a potential limitation. This was minimized by careful ascertainment of depression and dementia cases, exclusion of individuals with suspected dementia at baseline and those who developed dementia within 3 years after baseline, and controlling for various important confounders. CONCLUSIONS: Risk of incident dementia varies with presence and resolution of depression at different ages. Further studies are needed to test whether treating adult-onset depression may prevent dementia. Older adults with a history of depression present for an extended time should be monitored for cognitive decline.

Effect of physical exercise and medication on enhancing cognitive function in older adults with vascular risk.

AIM: To examine the association of physical exercise (PE) and medication on cognitive function in older adults with vascular risk. METHODS: This was a cross-sectional study of 478 non-demented participants aged ≥60 years with vascular risk. Management strategy included PE (mind-body exercise and/or strenuous exercise), medication, PE combined with medication and no management at all. Participation of PE was determined by self-reporting exercise engagement in the past year. Cognitive preservation was defined as a global composite z-score that was equal to or above the age and educational adjusted mean of cognitively normal older adults. Binary logistic regression was carried out to examine the association between management strategy and cognitive preservation in each exercise modality adjusted by sociodemographic, physical, mental and genetic factors. RESULTS: An association was found in preserved cognitive function for those who managed their vascular risk through PE (OR 2.5, 95% CI 1.2-5.3, P = 0.015) and in combination with medication (OR 2.1, 95% CI 1.0-4.6, P = 0.05). A similar pattern was also found in each exercise subtype. A significant short-term (OR 3.6, 95% CI 1.0-12.4, P = 0.042) to lifelong (OR 3.5, 95% CI 1.4-8.5, P = 0.006) cognitive benefit was found in MB exercise. CONCLUSION: Medication alone may be insufficient to preserve cognitive function in older adults with vascular risk. In our sample, medication in combined with PE is found to have significant impact on cognitive improvement. Mind-body exercise might be better than strenuous exercise, as a more sustainable cognitive effect is observed. Geriatr Gerontol Int 2020; 20: 1067-1071..

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

BACKGROUND: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). METHODS: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. RESULTS: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. CONCLUSION: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Validation of a computerized Hong Kong - vigilance and memory test (HK-VMT) to detect early cognitive impairment in healthy older adults.

Objectives: Hong Kong - Vigilance and Memory Test (HK-VMT) is developed to distinguish early cognitive impairment in the pre-symptomatic phase from normal cognitive ageing in older adults. The objectives were to validate HK-VMT to differentiate mild cognitive impairment (MCI) and healthy control (HC), and to explore the cut-off scores for different educational levels.Method: A total of 606 older adults underwent the HK-VMT and conventional cognitive tests. HK-VMT is a 15 minutes cognitive battery that assesses episodic memory, attention, and visuospatial ability. The HK-VMT total is the sum of accuracy of all subtests with a range of 0 to 40. Differences in socio-demographic and clinical characteristics between groups were explored. Receiver operating characteristic (ROC) analyses were used to compare HK-VMT and Cantonese Mini Mental State Examination (CMMSE). A sample of 50 participants repeated the HK-VMT in 1 month to evaluate test-retest reliability.Results: ROC analysis of Area Under Curve (AUC) demonstrated that HK-VMT (AUC 0.793) was comparable to CMMSE (AUC 0.748) in differentiating MCI from HC in a matched sample. A cutoff at 21/22 was chosen yielding a sensitivity of 86.1% and a specificity of 75.3% for differentiating MCI and HC. Test-retest reliability of HK-VMT total was 0.71 (p<.001) in a month time.Conclusion: HK-VMT has demonstrated satisfactory validity in detecting cognitive impairment with good test-retest reliability in local older adults. It also performed favourably in the highly educated group when compared to CMMSE.

Efavirenz use and neurocognitive performance among older people living with HIV who were on antiretroviral therapy.

This study was to compare global and domain-specific neurocognitive performance between older people living with HIV (PLWH) taking/not taking efavirenz (EFV) and HIV-negative controls. A cross-sectional study was conducted in Yongzhou city, China. All PLWH older than 50 years listed on the registry of Centres for Disease Control and Prevention were invited to join the study. Frequency matching was used to sample HIV-negative controls according to the distribution of age, sex, and years of formal education of older PLWH. A total of 308 older PLWH and 350 HIV-negative controls completed the face-to-face interview and neurocognitive assessment using the comprehensive neuropsychological test battery. After adjusting for significant confounders, older PLWH taking EFV showed poorer performance in memory (p = 0.020), verbal fluency (p = 0.002), and poorer global neurocognitive performance (p = 0.032) than those without EFV use. Compared to HIV-negative controls, older PLWH taking EFV had poorer performance in all neurocognitive domains (p values: <0.001-0.003) and poorer global neurocognitive performance (p < 0.001). Similar trends were observed when comparing older PLWH without using EFV versus HIV-negative controls, with the exception of verbal fluency (p = 0.560). Health care workers should monitor the neuropsychological performance of older PLWH, epically those who were taking EFV. Longitudinal studies are warranted.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Loneliness interacts with family relationship in relation to cognitive function in Chinese older adults.

ABSTRACTObjectives:Loneliness and social networks have been extensively studied in relation to cognitive impairments, but how they interact with each other in relation to cognition is still unclear. This study aimed at exploring the interaction of loneliness and various types of social networks in relation to cognition in older adults. DESIGN: a cross-sectional study. SETTING: face-to-face interview. PARTICIPANTS: 497 older adults with normal global cognition were interviewed. MEASUREMENTS: Loneliness was assessed with Chinese 6-item De Jong Gierverg's Loneliness Scale. Confiding network was defined as people who could share inner feelings with, whereas non-confiding network was computed by subtracting the confiding network from the total network size. Cognitive performance was expressed as a global composite z-score of Cantonese version of mini mental state examination (CMMSE), Categorical verbal fluency test (CVFT) and delayed recall. Linear regression was used to test the main effects of loneliness and the size of various networks, and their interaction on cognitive performance with the adjustment of sociodemographic, physical and psychological confounders. RESULTS: Significant interaction was found between loneliness and non-confiding network on cognitive performance (B = .002, ß = .092, t = 2.099, p = .036). Further analysis showed a significant interaction between loneliness and the number of family members in non-confiding network on cognition (B = .021, ß = .119, t = 2.775, p = .006). CONCLUSIONS: Results suggested that a non-confiding relationship with family members might put lonely older adults at risk of cognitive impairment. Our study might have implications on designing psychosocial intervention for those who are vulnerable to loneliness as an early prevention of neurocognitive impairments.

Mapping the Proxies of Memory and Learning Function in Senior Adults with High-performing, Normal Aging and Neurocognitive Disorders.

BACKGROUND: Memory and learning, as the core brain function, shows controversial results across studies focusing on aging and dementia. One of the reasons is because of the multi-faceted nature of memory and learning. However, there is still a dearth of comparable proxies with psychometric and morphometric portrait in clinical and non-clinical populations. OBJECTIVE: We aim to investigate the proxies of memory and learning function with direct and derived measures and examine their associations with morphometric features in senior adults with different cognitive status. METHODS: Based on two modality-driven tests, we assessed the component-specific memory and learning in the individuals with high performing (HP), normal aging, and neurocognitive disorders (NCD) (n = 488). Structural magnetic resonance imaging was used to measure the regional cortical thickness with surface-based morphometry analysis in a subsample (n = 52). METHODS: Compared with HP elderly, the ones with normal aging and minor NCD showed declined recognition memory and working memory, whereas had better learning performance (derived scores). Meanwhile, major NCD patients showed more breakdowns of memory and learning function. The correlation between proxies of memory and learning and cortical thickness exhibited the overlapped and unique neural underpinnings. CONCLUSIONS: The proxies of memory and learning could be characterized by component-specific constructs with psychometric and morphometric bases. Overall, the constructs of memory are more likely related to the pathological changes, and the constructs of learning tend to reflect the cognitive abilities of compensation.

Anxiety symptoms predicted decline in episodic memory in cognitively healthy older adults: A 3-year prospective study.

OBJECTIVE: Prospective studies on late-life anxiety disorders suggested that history of anxiety symptoms may be predictive of cognitive decline in old age. However, the relationship between anxiety and cognitive decline is still inconclusive due to heterogeneity in sample and methodology. This study was to explore how baseline anxiety symptoms associated with the change of memory in older people without cognitive impairment over a 3-year period. METHODS: This was a 3-year prospective study on 91 cognitively normal older adults with anxiety symptoms. They were matched with 91 controls based on age, gender, and education. Anxiety symptoms were assessed with Revised Clinical Interview Schedule (CIS-R). Physical health was assessed with Chronic Illness Rating Scale (CIRS). Cognitive performance was measured using Cantonese version of the mini-mental state examination (CMMSE); 10-minute delay recall; Category verbal fluency test (CVFT); Trail making tests (TMT); and digit and visual span tests. Outcomes were determined as the change of cognitive performance over a 3-year period. RESULTS: As expected, anxiety group had higher score in CIRS score (t = 4.45, P < .001) and CIS-R score (t = 9.24, P < .001) than control group. Linear regression showed that baseline anxiety symptoms were associated with change in delayed recall (B = 0.77, P = 0.027, 95% CI = 0.09-1.46), after adjusting for cognitive performance, physical, and mental health statuses. CONCLUSIONS: Anxious healthy older adults showed specific decline in episodic memory over a 3-year interval. Our result suggested that anxiety symptoms are predictive of episodic memory decline in cognitively healthy older adults and may be an early sign of neurodegenerative disorders.

Beyond a Differential Diagnosis: Cognitive and Morphometric Decoding of Information Processing Speed in Senior Adults with DSM-5 Mild Neurocognitive Disorders.

BACKGROUND: Processing speed has been highlighted as a diagnostic item for neurocognitive disorders (NCD) in DSM-5. The utility of information processing speed (IPS) enclosed with multiscale constructs in the diagnosis of NCD warrants exploration. OBJECTIVE: We aimed to investigate the IPS with two types of measurements in the patients with NCD due to vascular disease (NCD-vascular) and NCD due to Alzheimer's disease (NCD-AD), and examine the associations between IPS measures and morphometric features. METHODS: The IPS was evaluated using trail making test (TMT) and flanker test (n = 204). Direct scores, derived scores, and reaction time (RT) were used as IPS measures. Further, surface-based morphometry cortical volume was calculated in a subsample (n = 44) with structural MRI data. RESULTS: All IPS measures showed a significant value to differentiate NCD patients from healthy subjects. Only mean RT could distinguish NCD-AD from NCD-vascular groups. TMT-B score and difference score were correlated with gray matter volume (GMV) of inferior frontal gyrus, precuneus and superior temporal cortex. Mean RT was associated with the GMV of post-central gyrus (r = -0.327, p = 0.035), and executive speed was associated with inferior frontal cortex (r = -0.475, p = 0.001), cingulate gyrus (r = -0.497, p = 0.001), and superior temporal gyrus (r = -0.36, p = 0.019). CONCLUSION: The cognitive and morphometric correlates of IPS measures indicate that complex IPS might be decomposed into the domain-specific components with corresponding neural underpinnings. Our findings may also provide essential insights into the diagnostic item of NCD.