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.

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.

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.

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.

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..

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.

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.

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.

A cross-sectional study on clinical correlates of anxiety disorders in 613 community living older adults in Hong Kong.

OBJECTIVES: Previous studies have reported that the prevalence of late life anxiety disorders varies between 3.2% and 15.3%. Despite its high prevalence, anxiety disorders are still under-recognized in old age. This study evaluated the association among health, psychosocial factors, lifestyle choices, cognitive function and anxiety disorders in the older population in Hong Kong. METHODS: Six hundred and thirteen volunteer participants aged 60 years or above were interviewed for their socio-demographic background, physical and mental health statuses, social network, cognitive function and their activity engagement style. Ascertainment of diagnosis of anxiety disorders was based on the use of ICD-10 diagnostic criteria generated by the Revised Clinical Interview Schedule (CIS-R) algorithms. RESULTS: According to the ICD-10 diagnostic criteria generated by the CIS-R algorithms, 4.4% (N = 27) had mixed anxiety and depressive disorder, 2.5% (N = 15) had generalized anxiety disorders and 0.2% (N = 1) had other anxiety disorders (Phobia). Individuals with anxiety disorders had more gastrointestinal conditions (OR = 2.66, 95% CI 1.48-4.76) and genitourinary problems (OR = 1.96, 95% CI 1.05-3.65), poor 10-min delayed recall (OR = 0.68, 95% CI 0.56-0.83), worse abstract thinking (OR = 0.65, 95% CI 0.49-0.85) and poor social networking in confidante relationship (OR = 0.88, 95% CI 0.79-0.98). Lifestyle activity engagement was not associated with the presence of anxiety disorders. CONCLUSIONS: Older adults with anxiety disorders appeared to have greater medical comorbidity and lower cognitive function. While anxiety may affect memory performance, future studies are needed to explore if anxiety symptom may reflect early neurodegeneration that easily escapes clinical attention. Copyright © 2016 John Wiley & Sons, Ltd.

Prevalence of anxiety disorders in community dwelling older adults in Hong Kong.

BACKGROUND: Anxiety disorders are prevalent yet under-recognized in late life. We examined the prevalence of anxiety disorders in a representative sample of community dwelling older adults in Hong Kong. METHOD: Data on 1,158 non-demented respondents aged 60-75 years were extracted from the Hong Kong Mental Morbidity survey (HKMMS). Anxiety was assessed with the revised Clinical Interview Schedule (CIS-R). RESULT: One hundred and thirty-seven respondents (11.9%, 95% CI = 10-13.7%) had common mental disorders with a CIS-R score of 12 or above. 8% (95% CI = 6.5-9.6%) had anxiety, 2.2% (95% CI = 1.3-3%) had an anxiety disorder comorbid with depressive disorder, and 1.7% (95% CI = 1-2.5%) had depression. Anxious individuals were more likely to be females (χ 2 = 25.3, p < 0.001), had higher chronic physical burden (t = -9.3, p < 0.001), lower SF-12 physical functioning score (t = 9.2, p < 0.001), and poorer delayed recall (t = 2.3, p = 0.022). The risk of anxiety was higher for females (OR 2.8, 95% C.I. 1.7-4.6, p < 0.001) and those with physical illnesses (OR 1.4, 95% C.I. 1.3-1.6, p < 0.001). The risk of anxiety disorders increased in those with disorders of cardiovascular (OR 1.9, 95% C.I. 1.2-2.9, p = 0.003), musculoskeletal (OR 2.0, 95% C.I. 1.5-2.7, p < 0.001), and genitourinary system (OR 2.0, 95% C.I. 1.3-3.2, p = 0.002). CONCLUSIONS: The prevalence of anxiety disorders in Hong Kong older population was 8%. Female gender and those with poor physical health were at a greater risk of developing anxiety disorders. Our findings also suggested potential risk for early sign of memory impairment in cognitively healthy individuals with anxiety disorders.

Would older adults with mild cognitive impairment adhere to and benefit from a structured lifestyle activity intervention to enhance cognition?: a cluster randomized controlled trial.

BACKGROUND: Epidemiologic evidence suggests that cognitive and physical activities are associated with better cognition in late life. The present study was conducted to examine the possible benefits of four structured lifestyle activity interventions and compare their effectiveness in optimizing cognition for older adults with mild cognitive impairment (MCI). METHOD AND FINDINGS: This was a 12-month cluster randomized controlled trial. 555 community-dwelling Chinese older adults with MCI (295 with multiple-domain deficits (mdMCI), 260 with single-domain deficit (sdMCI)) were recruited. Participants were randomized into physical exercise (P), cognitive activity (C), integrated cognitive and physical exercise (CP), and social activity (S, active control) groups. Interventions comprised of one-hour structured activities three times per week. Primary outcome was Clinical Dementia Rating sum of boxes (CDR-SOB) scores. Secondary outcomes included Chinese versions of Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), delayed recall, Mini-Mental State Examination, Category Verbal Fluency Test (CVFT) and Disability Assessment for Dementia - Instrumental Activities of Daily Living (DAD-IADL). Percentage adherence to programs and factors affecting adherence were also examined. At 12th month, 423 (76.2%) completed final assessment. There was no change in CDR-SOB and DAD-IADL scores across time and intervention groups. Multilevel normal model and linear link function showed improvement in ADAS-Cog, delayed recall and CVFT with time (p<0.05). Post-hoc subgroup analyses showed that the CP group, compared with other intervention groups, had more significant improvements of ADAS-Cog, delayed recall and CVFT performance with sdMCI participants (p<0.05). Overall adherence rate was 73.3%. Improvements in ADAS-Cog and delayed recall scores were associated with adherence after controlling for age, education, and intervention groups (univariate analyses). CONCLUSIONS: Structured lifestyle activity interventions were not associated with changes in everyday functioning, albeit with some improvements in cognitive scores across time. Higher adherence was associated with greater improvement in cognitive scores. Factors to enhance adherence should be specially considered in the design of psychosocial interventions for older adults with cognitive decline. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR-TRC-11001359.

Bias in discriminating very mild dementia for older adults with different levels of education in Hong Kong.

BACKGROUND: Education has a profound effect on older adults' cognitive performance. In Hong Kong, some dementia screening tasks were originally designed for developed population with, on average, higher education. METHODS: We compared the screening power of these tasks for Chinese older adults with different levels of education. Community-dwelling older adults who were healthy (N = 383) and with very mild dementia (N = 405) performed the following tasks: Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive subscales, Verbal Fluency, Abstract Thinking, and Visual/Digit Span. Logistic regression was used to examine the power of these tasks to predict Clinical Dementia Rating (CDR 0.5 vs. 0). RESULTS: Logistic regression analysis showed that while the screening power of the total scores in all tasks was similar for high and low education groups, there were education biases in some items of these tasks. CONCLUSION: The differential screening power in high and low education groups was not identical across items in some tasks. Thus, in cognitive assessments, we should exercise great caution when using these potentially biased items for older adults with limited education.

Estrogen receptor α polymorphisms and the risk of cognitive decline: A 2-year follow-up study.

OBJECTIVE: The neuroprotective role of estrogen is supported by biochemical studies, but the results from clinical trials of estrogen replacement therapy on cognitive decline are controversial. One possible missing link might be the interindividual difference in estrogen receptor expression. In this study, the association of estrogen receptor α (ESR1) polymorphisms and cognitive decline was investigated. METHODS: Chinese older adults (n = 284) were recruited, and the cognitive profile was follow-up over 2-year period. Twenty ESR1 polymorphisms were investigated and correlated with the cognitive decline for the subjects. RESULTS: Significant association was found between ESR1 polymorphisms (rs9340799 [ESR1+351], rs1801132 [ESR1+975], rs6557171, rs9397456, and rs1884049) and subjects with no dementia (Clinical Dementia Rating, CDR 0) and very mild dementia (CDR 0.5). Several ESR1 polymorphisms were associated with cognitive decline as assessed by Chinese versions of Mini-Mental State Examination and Alzheimer Disease Association Scales-Cognitive Subscale. Different sets of ESR1 polymorphisms were associated with cognitive decline from CDR 0 to 0.5 and CDR 0.5 to 1. ESR1 polymorphisms (rs3853248, rs22334693 [ESR1+397], rs9340799 [ESR1+351], rs9397456, rs1801132 [ESR1+975], rs2179922, rs932477, and rs9341016) were associated with the deterioration of episodic memory among subjects with baseline CDR 0, indicating these polymorphisms might be markers for episodic memory decline at an earlier stage. CONCLUSION: This study showed association between ESR polymorphisms and cognitive decline or specific areas in cognitive profile. These findings might be useful in identifying individuals at risk for early intervention, and more research is required to elucidate the underlying mechanisms.

Capacity to make decisions on medication management in Chinese older persons with mild cognitive impairment and mild Alzheimer's disease.

BACKGROUND: This study aimed to assess if decisional capacity and the four decision-making abilities related to decisions concerning medication management were impaired among community-dwelling Chinese older persons in Hong Kong with amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD), as compared with cognitively normal older adults. METHODS: Two hundred and ninety-one Chinese community-dwelling older adults were recruited. The four decision-making abilities and decisional capacity were assessed by using the Chinese version of the Assessment of Capacity for Everyday Decision-Making (ACED) and independent clinician ratings based on the definition in the UK Mental Capacity Act 2005, respectively. RESULTS: Ninety-nine participants (34%) were diagnosed with MCI and ninety-five (33%) with mild AD. Although almost all (96%) of the participants in the MCI group were found to be mentally competent to make decisions on medication management in clinician ratings, their decision-making abilities as measured by the ACED were significantly lower than those of the cognitively normal controls. CONCLUSIONS: Results from this study suggest that abilities related to decisions on medication management are impaired before the clinical diagnosis of dementia is made. Use of specific and structured assessment of the relevant decisional abilities may enhance clinical judgment.

Examining the association between late-life leisure activity participation and global cognitive decline in community-dwelling elderly Chinese in Hong Kong.

OBJECTIVE: This study examines the association between late-life leisure activity participation and global cognitive decline in community-dwelling elderly Chinese in Hong Kong. METHODS: Five hundred and five participants, not clinically demented at the baseline, were analysed in the follow-up study of a population-based community survey among Hong Kong Chinese aged 60 and over. Information regarding leisure activity participation, global cognitive function and important sociodemographic variables was collected. Late life leisure activity profiles were classified into intellectual, social, physical and recreational categories, and were measured by total hours per week, total frequency and total number of subtypes. Multivariate logistic regression analyses were used to evaluate the association between leisure activity participation at the baseline and the incidence of global cognitive decline at the 22-month follow-up. The incidence of global cognitive decline was defined as a one-point drop in z-score of the Cantonese version of the mini-mental state examination (CMMSE). RESULTS: At the follow-up, a higher level of participation in intellectual activities was significantly associated with a lower incidence of global cognitive decline as measured by both the total hours per week (multivariate-adjusted OR 0.97 (95% CI 0.94-0.99, p=0.003)), and the total number of subtypes (multivariate-adjusted OR 0.74 (95% CI 0.58-0.95, p=0.018)). CONCLUSIONS: A higher level of late-life intellectual activity participation was associated with less global cognitive decline among community-dwelling elderly Chinese in Hong Kong.