Dysregulated Lymphocyte Antigen Receptor Signaling in Common Variable Immunodeficiency with Granulomatous Lymphocytic Interstitial Lung Disease.

PURPOSE: A subset of common variable immunodeficiency (CVID) patients either presents with or develops autoimmune and lymphoproliferative complications, such as granulomatous lymphocytic interstitial lung disease (GLILD), a major cause of morbidity and mortality in CVID. While a myriad of phenotypic lymphocyte derangements has been associated with and described in GLILD, defects in T and B cell antigen receptor (TCR/BCR) signaling in CVID and CVID with GLILD (CVID/GLILD) remain undefined, hindering discovery of biomarkers for disease monitoring, prognostic prediction, and personalized medicine approaches. METHODS: To identify perturbations of immune cell subsets and TCR/BCR signal transduction, we applied mass cytometry analysis to peripheral blood mononuclear cells (PBMCs) from healthy control participants (HC), CVID, and CVID/GLILD patients. RESULTS: Patients with CVID, regardless of GLILD status, had increased frequency of HLADR+CD4+ T cells, CD57+CD8+ T cells, and CD21lo B cells when compared to healthy controls. Within these cellular populations in CVID/GLILD patients only, engagement of T or B cell antigen receptors resulted in discordant downstream signaling responses compared to CVID. In CVID/GLILD patients, CD21lo B cells showed perturbed BCR-mediated phospholipase C gamma and extracellular signal-regulated kinase activation, while HLADR+CD4+ T cells and CD57+CD8+ T cells displayed disrupted TCR-mediated activation of kinases most proximal to the receptor. CONCLUSION: Both CVID and CVID/GLILD patients demonstrate an activated T and B cell phenotype compared to HC. However, only CVID/GLILD patients exhibit altered TCR/BCR signaling in the activated lymphocyte subsets. These findings contribute to our understanding of the mechanisms of immune dysregulation in CVID with GLILD.

Effect of attachment site on stability of cleavable antibody drug conjugates.

The systemic stability of the antibody-drug linker is crucial for delivery of an intact antibody-drug conjugate (ADC) to target-expressing tumors. Linkers stable in circulation but readily processed in the target cell are necessary for both safety and potency of the delivered conjugate. Here, we report a range of stabilities for an auristatin-based payload site-specifically attached through a cleavable valine-citrulline-p-aminobenzylcarbamate (VC-PABC) linker across various sites on an antibody. We demonstrate that the conjugation site plays an important role in determining VC-PABC linker stability in mouse plasma, and that the stability of the linker positively correlates with ADC cytotoxic potency both in vitro and in vivo. Furthermore, we show that the VC-PABC cleavage in mouse plasma is not mediated by Cathepsin B, the protease thought to be primarily responsible for linker processing in the lysosomal degradation pathway. Although the VC-PABC cleavage is not detected in primate plasma in vitro, linker stabilization in the mouse is an essential prerequisite for designing successful efficacy and safety studies in rodents during preclinical stages of ADC programs. The divergence of linker metabolism in mouse plasma and its intracellular cleavage offers an opportunity for linker optimization in the circulation without compromising its efficient payload release in the target cell.

The principle of assessing mental capacity for enduring power of attorney.

With Hong Kong's rapidly ageing population, increasing numbers of people now have some form of cognitive impairment. Enduring power of attorney is a legal instrument that can allow individuals to manage their financial matters if they subsequently become mentally incapacitated. The law requires that the mental capacity of the individual making an enduring power of attorney should be certified by a registered medical practitioner and a solicitor. This paper discusses the principles involved in the assessment of mental capacity for making an enduring power of attorney and uses this example to illustrate various important considerations in the formal assessment of mental capacity.

A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.

Lymphocyte-specific protein tyrosine kinase (LCK) is essential for T cell antigen receptor (TCR)-mediated signal transduction. Here, we report two siblings homozygous for a novel LCK variant (c.1318C>T; P440S) characterized by T cell lymphopenia with skewed memory phenotype, infant-onset recurrent infections, failure to thrive, and protracted diarrhea. The patients' T cells show residual TCR signal transduction and proliferation following anti-CD3/CD28 and phytohemagglutinin (PHA) stimulation. We demonstrate in mouse models that complete (Lck-/-) versus partial (LckP440S/P440S) loss-of-function LCK causes disease with differing phenotypes. While both Lck-/- and LckP440S/P440S mice exhibit arrested thymic T cell development and profound T cell lymphopenia, only LckP440S/P440S mice show residual T cell proliferation, cytokine production, and intestinal inflammation. Furthermore, the intestinal disease in the LckP440S/P440S mice is prevented by CD4+ T cell depletion or regulatory T cell transfer. These findings demonstrate that P440S LCK spares sufficient T cell function to allow the maturation of some conventional T cells but not regulatory T cells-leading to intestinal inflammation.

Structured assessment of mental capacity to make financial decisions in Chinese older persons with mild cognitive impairment and mild Alzheimer disease.

Previous studies suggested that patients with mild cognitive impairment (MCI) or dementia can have impaired and declining financial skills and abilities. The purpose of this study is to test a clinically applicable method, based on the contemporary legal standard, to examine directly the mental capacity to make financial decisions and its component decision-making abilities among patients with MCI and early dementia. A total of 90 patients with mild Alzheimer disease (AD), 92 participants with MCI, and 93 cognitively normal control participants were recruited for this study. Their mental capacity to make everyday financial decisions was assessed by clinician ratings and the Chinese version of the Assessment of Capacity for Everyday Decision-Making (ACED). Based on the clinician ratings, only 53.5% were found to be mentally competent in the AD group, compared with 94.6% in the MCI group. However, participants with MCI had mild but significant impairment in understanding, appreciating, and reasoning abilities as measured by the ACED. The ACED provided a reliable and clinically applicable structured framework for assessment of mental capacity to make financial decisions.

NEDD9 gene polymorphism influences the risk of Alzheimer disease and cognitive function in Chinese older persons.

Neural precursor cell expressed, developmentally down-regulated (NEDD9) gene was a new candidate risk gene for Alzheimer disease (AD). The CC genotype of a single nucleotide polymorphism rs760678 within this gene was associated with increasing risk of AD in a large study with white population. Our study aimed to replicate the initial report in Chinese population and explore its effect on cognitive performance. A total of 262 patients with AD, 293 patients with mild cognitive impairment, and 434 cognitive intact controls were recruited in the study. The result showed that G allele had a greater risk of AD (χ for trend test=5.61, df 1, P=0.018). The effects were mainly observed among Apolipoprotein E (APOE) ε4 noncarriers (χ for trend test=4.30, df 1, P=0.038). After adjustment of sex, age, education year, and APOE ε4 status by logistic regression, significant association between NEDD9 GG genotype and AD remained [OR=2.04, 95% confidence interval (CI)=1.02-4.08, P=0.044]. The scores of Cantonese version of the Mini-mental State Examination and Alzheimer's Disease Assessment Subscale-Cognitive subscale were associated with N polymorphism after adjusting for sex, age, education year, and ApoE ε4 status (Linear regression model, P<0.05). Our study identified rs760678 within NEDD9 gene in association with the risk of AD and cognitive performance in Chinese older persons. The fact that different alleles accounted for the risk in different population might suggest that there were ethnic group specific haplotypes that were primarily responsible for the predisposition.

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.

Interim follow-up of a randomized controlled trial comparing Chinese style mind body (Tai Chi) and stretching exercises on cognitive function in subjects at risk of progressive cognitive decline.

OBJECTIVES: We reported the interim findings of a randomized controlled trial (RCT) to examine the effects of a mind body physical exercise (Tai Chi) on cognitive function in Chinese subjects at risk of cognitive decline. SUBJECTS: 389 Chinese older persons with either a Clinical Dementia Rating (CDR 0.5) or amnestic-MCI participated in an exercise program. The exercise intervention lasted for 1 year; 171 subjects were trained with 24 forms simplified Tai Chi (Intervention, I) and 218 were trained with stretching and toning exercise (Control, C). The exercise comprised of advised exercise sessions of at least three times per week. RESULTS: At 5th months (2 months after completion of training), both I and C subjects showed an improvement in global cognitive function, delayed recall and subjective cognitive complaints (paired t-tests, p < 0.05). Improvements in visual spans and CDR sum of boxes scores were observed in I group (paired t-tests, p < 0.001). Three (2.2%) and 21(10.8%) subjects from the I and C groups progressed to dementia (Pearson chi square = 8.71, OR = 5.34, 95% CI 1.56-18.29). Logistic regression analysis controlled for baseline group differences in education and cognitive function suggested I group was associated with stable CDR (OR = 0.14, 95%CI = 0.03-0.71, p = 0.02). CONCLUSIONS: Our interim findings showed that Chinese style mind body (Tai Chi) exercise may offer specific benefits to cognition, potential clinical interests should be further explored with longer observation period.

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.

Prevalence of neuropsychiatric symptoms in chinese older persons with mild cognitive impairment-a population-based study.

OBJECTIVES: To estimate the point prevalence and correlates of neuropsychiatric (NP) symptoms among older adults with mild cognitive impairment (MCI) and normal cognition (NC) in a Chinese community. DESIGN: Cross-sectional study derived from a population-based prevalence study of MCI and dementia. SETTING AND PARTICIPANTS: This survey was conducted in Hong Kong from 2005 to 2006. Seven hundred eighty-eight community-dwelling older adults (450 NC and 338 MCI) were recruited. Cognitive and NP data were obtained. RESULTS: The point prevalence of at least one NP symptom in NC and MCI were 29% and 36.7%, respectively (logistic regression controlled for age and education, odds ratio = 1.38, 95% confidence interval [CI]: 1.01-1.89, Wald χ = 4.10, df = 1, p = 0.04). Agitation (1.8% versus 5.1%), apathy (7.6% versus 15.2%), and irritability (4.2% versus 8%) were more prevalent in subjects with MCI (p <0.05). Logistic regression analyses showed that apathy score was a significant factor associated with the status of NC or MCI (logistic regression, apathy, p = 0.031, Exp(B) = 1.23, 95% CI: 1.02-1.47; Hosmer and Lemeshow test, χ = 8.6, df = 8, p = 0.38, R = 0.23). CONCLUSIONS: The authors reported the findings of one of the first population-based studies estimating the point prevalence of NP symptoms in Asian older adults with MCI. Taking into account of its prevalence and magnitude of effects, apathy is a clinically significant symptom in MCI. Its predictive value for conversion to dementia warrants further evaluation.

Combined clinical and cognitive criteria to identify mild cognitive impairment in a southern Chinese community.

Mild Cognitive Impairment (MCI) is a recognized risk condition for clinical dementia. This paper attempted to explore the applicability of a combined cognitive and clinical approach to identify older Chinese adults at-risk of cognitive decline. Seven hundred forty randomly recruited community dwelling participants (aged 60 or over) were assessed at baseline and 2 years with Clinical Dementia Rating (CDR) and a cognitive battery. Baseline MCI groups were categorized by CDR-MCI, cognitive function (Cog-MCI), and a combined CDR-Cog approach. The cognitive approach adopted the Mayo clinic criteria. For the combined approach, nonamnestic MCI combined CDR 0.5 plus nonmemory cognitive deficits. The overall concordance between CDR and Cognitive test ratings were 65.3% (χ2 = 256.4, P<0.001, κ=0.44). With a combined approach, 424 (57%) participants were classified as normal. CDR-MCI group had higher cognitive scores compared with MCI groups by other criteria (1 way analysis of variance or ANOVA). At 2 years, the combined CDR-Cog MCI group identified all dementia (N=24) converters although group differences were not significant. Cognitive function and CDR identified participants potentially at-risk for furthermore decline, but exhibited some differences in detection profiles. A combined approach may be more practical in screening for MCI participants with diverse educational and cultural background.

Serum zinc is decreased in Alzheimer's disease and serum arsenic correlates positively with cognitive ability.

Zinc, copper, and iron aggregate Abeta and accumulate in Alzheimer's disease (AD) plaques. Some metals are increased in AD vs. control serum. The authors examined levels of 12 metals in serum of 44 AD and 41 control subjects. Zinc decreased from 12.3 to 10.9 micromol/L (means, p = 0.0007). Arsenic positively correlated with Mini-Mental State Examination score (p < 0.0001). Zinc deposition in brain amyloid might deplete zinc from other body compartments, such as serum. The arsenic correlation might be caused by the major contribution of seafood consumption to intake of both arsenic and docosahexaenoic acid, of which the latter may delay AD.

Effectiveness of an individualized functional training program on affective disturbances and functional skills in mild and moderate dementia--a randomized control trial.

OBJECTIVES: We reported the findings of a randomized controlled trial (RCT) to examine the effects of an individualized functional enhancement program (FEP) on functional skills and mood symptoms in mild and moderate dementia. SUBJECTS & METHODS: 74 Chinese older persons with dementia were recruited into a skills training program by occupational therapists (OT). Thirty seven subjects were trained with an individualized selection of daily activities (FEP Intervention, I); 37 were trained with general occupational therapy (Control, C). The FEP comprised of twice weekly group sessions of skills training and problem solving using cognitive behavioral approach. RESULTS: At 1 month after completion of program, both I and C subjects showed an improvement in process skills of the assessment of motor and process skills (AMPS)(paired t-tests, p < 0.05). At 4 months post-program, the I group showed a further reduction of cornell scale for depression in dementia (CSDD) scores (paired t-test, p = 0.02); Apathy improved at 1 month post-training (p = 0.04), but deteriorated at 4 months (p = 0.01). Group differences in changes of mood and functional scores were not significant (ANVOCA, p > 0.05). CONCLUSIONS: The findings suggested a potential benefit for individualized occupational therapy. It should be tailor made with individual needs and continued for sustained effectiveness.

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 Alzheimer's 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.

Could hypothetical scenarios enhance understanding on decision for life-sustaining treatment in non-demented Chinese older persons?

BACKGROUND: With increasing longevity, there is an increasing need for medical professionals to face situations in which explanation for decision on life-sustaining treatment (LST) would be required. OBJECTIVES: As advance decision making for LST in case of severe medical illness may be unfamiliar for most of the Chinese elders, we aim to explore if procedures adopted to enhance the exposure to the issue concerned would bring about improvement in knowledge toward decision for LST. METHOD: This was a cross-sectional study. The design was divided into three sections: (i) a pre-scenario knowledge assessment, (ii) scenario exposure (relating issues of LST using case vignettes), and (iii) a post-scenario assessment. The pre- and post-scenario assessment comprises 10 questions, exploring the understanding toward basic issues related to LST. The scenario exposure comprises two hypothetical case vignettes describing situations demanding decisions for LST. The knowledge level toward LST was assessed and compared before and after the presentation of the two vignettes. RESULTS: One-hundred community dwelling older persons (aged over 60 years) were recruited. The scenario exposure improved the knowledge level of participants (paired samples t-test, p < 0.05). Participants who were younger and better educated were more likely to perform better in the knowledge test (bivariate correlation and logistic regression, p < 0.05). CONCLUSIONS: The results demonstrated that hypothetical scenarios may help to enhance and facilitate the understanding of LST. The study should be carried forward to explore the applicability of enhancement procedure to facilitate the decision making for advance directives and LST in the older community.

Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity.

Lymphocyte migration is essential for the function of the adaptive immune system, and regulation of T cell entry into tissues is an effective therapy in autoimmune diseases. Little is known about the specific role of cytoskeletal effectors that mediate mechanical forces and morphological changes essential for migration in complex environments. We developed a new Formin-like-1 (FMNL1) knock-out mouse model and determined that the cytoskeletal effector FMNL1 is selectively required for effector T cell trafficking to inflamed tissues, without affecting naïve T cell entry into secondary lymphoid organs. Here, we identify a FMNL1-dependent mechanism of actin polymerization at the back of the cell that enables migration of the rigid lymphocyte nucleus through restrictive barriers. Furthermore, FMNL1-deficiency impairs the ability of self-reactive effector T cells to induce autoimmune disease. Overall, our data suggest that FMNL1 may be a potential therapeutic target to specifically modulate T cell trafficking to inflammatory sites.

Capacity to make treatment decisions in Chinese older persons with very mild dementia and mild Alzheimer disease.

OBJECTIVES: This study aims at assessing mental competence in Chinese patients with mild and very mild dementia with a semistructured assessment method and the impact of repeated presentations of information on patients' mental competence. DESIGN: Subjects with mild and very mild dementia were compared with cognitively intact subjects. SETTING: Chinese subjects were recruited from local social centers and residential hostels for the elderly in Hong Kong. PARTICIPANTS: Sixty-six Chinese community-dwelling older adults (aged from 65 to 87 years) were recruited. MEASUREMENTS: Clinical diagnosis was made by experienced geriatric psychiatrists. Subjects were assessed with the Mini-Mental State Examination and the Clinical Dementia Rating (CDR). Mental capacity to consent to treatment was assessed by using the Chinese version of the MacArthur Competence Assessment Tool-Treatment (MacCAT-T) and independent clinician ratings based on the definition in the Mental Capacity Act 2005 of the United Kingdom. RESULTS: Thirty-three (50%) participants were diagnosed with very mild or mild dementia (CDR = 0.5 or 1). In this group, 15 (45.5%) subjects were rated as mentally incompetent in clinician ratings. In the assessment of interrater reliability, the intraclass correlation coefficient of MacCAT-T summary scores among three raters ranged from 0.64 to 0.83. The MacCAT-T summary scores correlated significantly with clinician ratings, years of education, Mini-Mental State Examination score, and CDR. In contrast to the nonimpaired group, repeated presentation of information did not significantly improve capacity in the demented group. CONCLUSION: Results from this study suggest that even patients with very mild dementia in this population can show substantial deficits in decision-making capacity, and that improved capacity is not likely to result from repeated disclosure of information.

Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study.

OBJECTIVES: We previously found that the polymorphisms of cholesterol 24-hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese. However, its effect in predicting progression of cognitive decline remains unknown. METHODS: Two hundred and eighty-one Chinese subjects (121 cognitively intact, 101 with mild cognitive impairment and 59 with mildly dementia) were followed-up with a mean (SD) duration of 25.22(5.74) months. Association between the CYP46A1 gene polymorphisms and 2-year cognitive deterioration were evaluated. RESULTS: At follow-up, 225(80.0%) subjects were reassessed. Sixty-three subjects were diagnosed as AD, 68 were MCI and 94 were cognitively intact. Among them, 158 had improved or remained stable while 67 deteriorated. The 'deteriorated' group was older than 'improved or stable' group (t-test, t = -2.87, p < 0.001). IVS2-150 polymorphism was associated with a higher risk of cognitive deterioration. Subjects with T allele were more likely to deteriorate compared with those without T allele (Pearson chi(2) = 8.98, df 2, p = 0.011). IVS3-128 CC genotype was higher in 'improved or stable' group (Likelihood Ratio = 6.55, df 2, p = 0.038), suggesting a protective role for this allele. The two other polymorphisms, IVS1-192 and IVS4-122, did not show any significant association with cognitive function. CONCLUSION: CYP46A1 gene may act to modulate the course of cognitive deterioration in late life.

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

OBJECTIVE: 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. METHODS: Profiles of physical exercise was measured by a questionnaire (no exercise, stretching, aerobic and mind-body exercise). Cognitive Assessments included the CMMSE, ADAS-Cog, and Category Verbal Fluency Test (CVFT). RESULTS: The aerobic and mind body exercise groups with longer exercise habits (>5 years) had higher scores in most cognitive tests (Kruskal Wallis tests, p < 0.01). Beneficial effects were more significant in the young old group from 65- 75 years. CONCLUSIONS: Possible age related specific effects of aerobic and mind body exercise on cognitive reserve are worthy of further exploration.