Cindy W. C. Tam

Prevalence of very mild and mild dementia in community-dwelling older Chinese people in Hong Kong

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.

A 1-year randomized controlled trial comparing mind body exercise (Tai Chi) with stretching and toning exercise on cognitive function in older Chinese adults at risk of cognitive decline.

OBJECTIVES To compare the effectiveness of Chinese-style mind-body exercise (24 forms simplified Tai Chi) versus stretching and toning exercise in the maintenance of cognitive abilities in Chinese elders at risk of cognitive decline. DESIGN A 1-year single-blind cluster randomized controlled trial. SETTINGS Community centers and residential homes for elders in Hong Kong. PARTICIPANTS A total of 389 subjects at risk of cognitive decline (Clinical Dementia Rating, CDR 0.5 or amnestic-MCI) participated in an exercise intervention program. INTERVENTION A total of 171 subjects were trained with Tai Chi (Intervention [I]) and 218 were trained with stretching and toning exercise (Control [C]). METHODS Cognitive and functional performance were assessed at the baseline, and at 5, 9, and 12 months. Data were analyzed using multilevel mixed models. Primary outcomes included progression to clinical dementia as diagnosed by DSM-IV criteria, and change of cognitive and functional scores. Secondary outcomes included postural balance measured by the Berg Balance Scale neuropsychiatric and mood symptoms measured by the Neuropsychiatric Inventory, and Cornell Scale for Depression in Dementia. RESULTS At 1 year, 92 (54%) and 169 (78%) participants of the I and C groups completed the intervention. Multilevel logistic regression with completers-only analyses controlled for baseline differences in education revealed that the I group had a trend for lower risk of developing dementia at 1 year (odds ratio 0.21, 95% CI 0.05-0.92, P = .04). The I group had better preservation of CDR sum of boxes scores than the C group in both intention-to-treat (P = .04) and completers-only analyses (P = .004). In completers-only analyses, the I group had greater improvement in delay recall (P = .05) and Cornell Scale for Depression in Dementia scores (P = .02). CONCLUSION Regular exercise, especially mind-body exercise with integrated cognitive and motor coordination, may help with preservation of global ability in elders at risk of cognitive decline; however, logistics to promote long-term practice and optimize adherence needs to be revisited.

Reduced Semantic Fluency as an Additional Screening Tool for Subjects with Questionable Dementia

Background: Subjective memory complaints in subjects with mild cognitive impairment may represent a genuine decline in episodic memory. This paper evaluates the neuropsychological correlates of the semantic fluency test in subjects with questionable dementia (QD). Methods: A total of 331 Chinese subjects (118 normal controls, NC, 150 with QD and 63 with mild Alzheimer’s disease, AD) were assessed with the Category Verbal Fluency Test (CVFT), the AD Assessment Scale – cognitive subscale (ADAS-Cog), and digit and verbal span tests. CVFT performance was evaluated in each Clinical Dementia Rating (CDR) group. The total number of exemplars, the subcategory and the category size generated were evaluated. Neuropsychological correlates of CVFT scores were computed. Results: Significant differences in CVFT performance were found between the different CDR groups. The subjects with QD had intermediate scores compared to the NC and AD subjects (1-way ANOVA, p < 0.001, post-hoc Bonferroni comparisons). In NC the CVFT scores were significantly associated with ADAS-Cog total, and immediate and delayed recall scores (partial correlations controlled for age and education, p < 0.005). In the QD group the CVFT scores were correlated with ADAS-Cog total, and immediate recall and object naming scores (partial correlation controlled for age and education, p < 0.005). Regression analysis revealed that age and delayed recall were significant predictors of CVFT performance in NCs. In the QD group, age, ADAS-Cog immediate recall and object naming scores predicted the CVFT performance. Conclusions: The CVFT was impaired in the subjects with QD. Apart from episodic memory, semantic memory deficits also occur early in AD. The different cognitive predictors of CVFT scores in the NC and QD groups suggest that the test is associated with specific psychological functions at different stages of cognitive impairment.

A PIN1 polymorphism that prevents its suppression by AP4 associates with delayed onset of Alzheimer's disease

Alzheimers disease (AD), the most common form of dementia, is characterized by the presence of neurofibrillary tangles composed of tau and senile plaques of amyloid-beta peptides (Aβ) derived from amyloid precursor protein (APP). Pin1 is a unique prolyl isomerase that has been shown to protect against age-dependent neurodegeneration by acting on phosphorylated tau and APP to suppress tangle formation and amyloidogenic APP processing. Here we report a functional polymorphism, rs2287839, in the Pin1 promoter that is significantly associated with a 3-year delay in the average age at onset (AAO) of late-onset AD in a Chinese population. More significantly, the Pin1 polymorphism rs2287839 is located within the consensus binding motif for the brain-selective transcription factor, AP4 (CAGCTG) and almost completely abolishes the ability of AP4 to bind and suppress the Pin1 promoter, as shown by chromatin immunoprecipitation, electrophoretic mobility shift assay, and promoter luciferase assay. Moreover, overexpression or knockdown of AP4 resulted in an 80% reduction or 2-fold increase in endogenous Pin1 levels, respectively. Thus, AP4 is a novel transcriptional repressor of Pin1 expression and the Pin1 promoter single nucleotide polymorphism (SNP) identified in this study that prevents such suppression is associated with delayed onset of AD. These results indicate that regulation of Pin1 by AP4 plays a critical role in determining age at onset of AD and might be a novel therapeutic target to delay the onset of AD.

Neuropsychiatric symptoms are associated with increased risks of progression to dementia: a 2-year prospective study of 321 Chinese older persons with mild cognitive impairment

BACKGROUND studies have suggested that neuropsychiatric (NP) symptoms influence the development of dementia among older adults. But, the results are inconsistent and there is limited information about NP symptoms in population-based samples. OBJECTIVE to explore the association between NP symptoms and risk of cognitive decline in Chinese older persons residing in the community. DESIGN prospective study. SETTING community sample. SUBJECTS a total of 321 community-dwelling Chinese older persons aged 60 or over with mild cognitive impairment participated in the study. METHODS at baseline, each subject was assessed with Clinical Dementia Rating (CDR), Mini-Mental State Examination, list learning and delayed recall, and Category Verbal Fluency Test. Severity of NP symptoms was evaluated with Neuropsychiatric Inventory (NPI). Global cognitive status at the end of 2-year study period was determined by CDR. RESULTS at baseline, 40.5% of participants exhibited one or more NP symptoms (NPI total score ≥ 1). Night-time behaviours (22.1%), depression (16.8%), apathy (14.0%) and anxiety (12.8%) were the most common NP symptoms. At the end of 2-year follow-up, 27.5% of participants with depression at baseline developed dementia, compared with 14.8% of those without depression (χ² = 4.90, P= 0.03). Aberrant motor behaviour was also significantly associated with deterioration in cognition (χ² = 5.84, P= 0.02), although it was an infrequent occurrence. On logistic regression analysis, only depression at baseline was shown to be a risk factor for progression to dementia (OR= 2.40, 95% CI 1.05-5.46, P= 0.04). CONCLUSION depression in non-demented older persons may represent an independent dimension reflecting early neuronal degeneration. Further studies should be conducted to assess whether effective management of NP symptoms exerts beneficial effects on cognitive function.

Characteristic Profiles of Instrumental Activities of Daily Living in Chinese Older Persons with Mild Cognitive Impairment

Increasing evidence suggests that performance of the instrumental activities of daily living (IADL) can be impaired at the mild cognitive impairment (MCI) stage. Our study aimed at investigating the profiles of functional impairment in Chinese subjects with MCI. Subjects with MCI were categorized into single-domain amnestic MCI (a-MCI) (n = 54) and multiple-domain amnestic MCI (md-MCI) (n = 93) groups. Their functional scores of Disability Assessment of Dementia (DAD) were compared with those of cognitively normal elderly controls (NC) (n = 78) and those with mild Alzheimers disease (AD) (n = 85). Subjects with md-MCI had intermediate performance in IADL between the NC and those with mild AD. Subjects with a-MCI had functional scores similar to those of normal controls. Age, education, and global cognitive test scores were not associated with functional scores in MCI subjects. Our results demonstrated that Chinese older persons with md-MCI had impairment in IADL, as compared to NC and subjects with a-MCI. This finding suggests that assessment of IADL should be incorporated in the clinical evaluation of MCI.

Modality of physical exercise and cognitive function in Hong Kong older Chinese community

We reported the association between modality of Physical Exercise and cognitive function in 782 older Chinese adults assessed in the second phase of a population survey for dementia in Hong Kong.

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

This study examines the association between late‐life leisure activity participation and global cognitive decline in community‐dwelling elderly Chinese in Hong Kong.

Examining the association between participation in late-life leisure activities and cognitive function in community-dwelling elderly Chinese in Hong Kong

BACKGROUND Growing evidence suggests that participation in late-life leisure activity may have beneficial effects on cognitive function. The objective of the study was to evaluate the association between leisure activity participation and cognitive function in an elderly population of community-dwelling Hong Kong Chinese. METHODS 512 participants were assessed in the follow-up study of a population-based community survey of the prevalence of cognitive impairment among Hong Kong Chinese aged 60 years and over. Leisure activities were classified into four categories (physical, intellectual, social and recreational). Information regarding leisure activity participation, cognitive function and other variables was collected. Multivariate linear regression analyses were performed to examine the association between leisure activity participation and cognitive function. RESULTS A higher level of late-life leisure activity participation, particularly in intellectual activities, was significantly associated with better cognitive function in the elderly, as reflected by the results of the Cantonese Mini-mental State Examination (p = 0.007, 0.029 and 0.005), the Category Verbal Fluency Test (p = 0.027, 0.003 and 0.005) and digit backward span (p = 0.031, 0.002 and 0.009), as measured by the total frequency, total hours per week and total number of subtypes, respectively; the Chinese Alzheimers Disease Assessment Scale-Cognitive Subscale (p = 0.045) and word list learning (p = 0.003), as measured by the total number of subtypes; and digit forward span (p = 0.007 and 0.015), as measured by the total hours per week and total number of subtypes, respectively. CONCLUSION Late-life intellectual activity participation was associated with better cognitive function among community-dwelling Hong Kong elderly Chinese.

Executive Function Impairment in Community Elderly Subjects with Questionable Dementia

Background: The neurocognitive profile of community-dwelling Chinese subjects with ‘questionable’ dementia was studied. Methods: One hundred and fifty-four ambulatory Chinese subjects were recruited from local social centers for the elderly. Each subject was examined using the Clinical Dementia Rating (CDR), the Cantonese version of the Mini-Mental State Examination (CMMSE), the Chinese version of the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog), the Category Verbal Fluency Test (CVFT), digit and visual span tests, and the Cambridge Neurological Inventory. The neurocognitive profile of nondemented subjects (CDR 0) was compared with that of subjects with ‘questionable’ dementia (CDR 0.5). Results: Subjects with ‘questionable’ dementia were older, and had lower educational levels and global cognitive assessment scores than the controls (CMMSE and ADAS-Cog; t tests, p < 0.001). In addition, they also had significantly lower scores in delayed recall, reverse span, verbal fluency tests and worse performance in complex motor tasks related to executive function (Mann-Whitney tests, p < 0.001). Logistic regression analysis revealed that ADAS-Cog, CVFT, and reverse visual span were significant predictors for the CDR of ‘questionable’ dementia. Conclusion: Aside from memory impairment, executive function deficits were also present in subjects with ‘questionable’ dementia. To identify groups cognitively at risk for dementia, concomitant assessments of memory and executive function are suggested.