Alzheimer Disease: Stewart R

Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P, Anonymous00415. · Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #18667359 No free full text.

Abstract: Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

Stewart R. · Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. · Br J Psychiatry. · Pubmed #11823327 links to  free full text

Abstract: BACKGROUND: The concept of vascular dementia has a long history but its usefulness as a diagnostic category has been called into question. AIMS: To evaluate vascular disease as a risk factor for dementia and the interface between cerebrovascular pathology and Alzheimer's disease. METHOD: The literature on this topic was selectively reviewed and synthesised. RESULTS: Risk factors for cerebrovascular disease are also risk factors for dementia. However, the course of dementia, once it has developed, appears to be frequently determined by Alzheimer's disease. CONCLUSIONS: As a public health measure, modification of vascular risk represents a potentially powerful means to prevent dementia through delaying its onset. However, an effect on progression of dementia, once it has developed, has yet to be established. The traditional view of vascular dementia and Alzheimer's disease as distinguishable conditions is becoming steadily less tenable.

Stewart R, Prince M, Mann A. · Section of Old Age Psychiatry, Institute of Psychiatry, London, United Kingdom. · Aust N Z J Psychiatry. · Pubmed #10619206 No free full text.

Abstract: OBJECTIVE: We aim to summarise the recent and accumulating epidemiological research which suggests that cardiovascular disease and vascular risk factors play an important role as risk factors for Alzheimer's disease (AD) in later life. METHOD: The epidemiological literature is summarised in considering the evidence for such an association, focusing on optimally designed population-based studies. Potential mechanisms of association are considered, drawing on relevant findings from neuroscience. RESULTS: Cardiovascular disease and vascular risk disorders appear to be important factors in the aetiology of AD. However, there is a paucity of prospective studies with an adequate duration of follow-up to investigate the apparent age- and time-dependent nature of these associations. CONCLUSIONS: Vascular disorders represent potentially preventable risk factors with an important population impact due to their high prevalence in developed countries. The concept of AD and vascular dementia as clearly distinguishable disorders clinically or aetiologically is becoming increasingly tenuous. A better understanding of the relationship between AD and vascular disorders will depend on a more flexible diagnostic and conceptual framework.

Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY. · Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Department of Psychiatry, Taipei Medical University, Taipei, Taiwan. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #18573585 No free full text.

Abstract: A 24-week, randomized, double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants. Twenty three participants with mild or moderate Alzheimer's disease and twenty three with mild cognitive impairment were randomized to receive omega-3 PUFAs 1.8 g/day or placebo (olive oil). The data of 35 (76%) participants with at least one post-treatment visit was analyzed. There were no severe adverse effects in either group and it suggests that omega-3 PUFAs were well tolerable in this population. The treatment group showed better improvement on the Clinician's Interview-Based Impression of Change Scale (CIBIC-plus) than those in the placebo group over the 24 week follow-up (p=0.008). There was no significant difference in the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) change during follow-up in these two groups. However, the omega-3 fatty acids group showed significant improvement in ADAS-cog compared to the placebo group in participants with mild cognitive impairment (p=0.03), which was not observed in those with Alzheimer's disease. Higher proportions of eicosapentaenoic acid on RBC membranes were also associated with better cognitive outcome (p=0.003). Further studies should be considered with a larger-sample size, diet registration, higher dosages, comparisons between different combinations of PUFAs, and greater homogeneity of participants, especially those with mild Alzheimer's disease and mild cognitive impairment.

Kim JM, Stewart R, Kim SW, Shin IS, Yang SJ, Shin HY, Yoon JS. · Department of Psychiatry and Centre for Aging and Geriatrics, Chonnam National University Medical School, Kwangju, Republic of Korea. · J Neurol Neurosurg Psychiatry. · Pubmed #18252751 No free full text.

Abstract: OBJECTIVES: Prospective findings have not been consistent for folate, vitamin B(12) and homocysteine concentrations as predictors of dementia. This study aimed to investigate both baseline concentrations of folate, vitamin B(12) and homocysteine and changes in these concentrations as predictors/correlates of incident dementia. METHODS: Of 625 elderly patients without dementia at baseline, 518 (83%) were followed over a 2.4 year period and were clinically assessed for incident dementia and Alzheimer's disease (AD). Serum concentrations of folate, vitamin B(12) and homocysteine were measured at the baseline and follow-up assessments. Covariates included age, sex, education, disability, depression, alcohol consumption, physical activity, vascular risk factors, serum creatinine concentration, vitamin intake and weight change. RESULTS: Only baseline lower folate concentrations predicted incident dementia. The onset of dementia was significantly associated with an exaggerated decline in folate, a weaker increase in vitamin B(12) concentrations and an exaggerated increase in homocysteine concentrations over the follow-up period. These associations were reduced following adjustment for weight change over the same period. CONCLUSIONS: Incident dementia is more strongly associated with changes in folate, vitamin B(12) and homocysteine than with previous concentrations. These changes may be linked to other somatic manifestations of early dementia, such as weight loss.

Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Shin HY, Yoon JS. · Department of Psychiatry, Chonnam National University Medical School, Kwangju, Republic of Korea. · Int J Geriatr Psychiatry. · Pubmed #17932993 No free full text.

Abstract: BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR) c.677C>T (A222V) polymorphism and Alzheimer's disease (AD) is controversial. The objectives of the study were to investigate the association between MTHFR c.677C>T polymorphism and AD in Korean elders and to the extent to which it is modified by the major components of one-carbon metabolism and apolipoprotein E (APOE) genotype. METHODS: Seven hundred and thirty-two community residents aged 65 or over were clinically assessed for AD. Genotyping was performed for MTHFR c.677C>T and APOE; serum levels of folate, vitamin B(12), and homocysteine were assayed. Age, gender and education were included as covariates. RESULTS: A trend of association between TT genotype of MTHFR c.677C>T and AD was found [adjusted OR (95% CI): 1.73 (0.80-3.74)]. The association was significant in the presence of below-median vitamin B(12) level [3.66 (1.14-11.71)] and in APOE e4 non-carriers [2.97 (1.00-8.55)] with significant interaction terms, and bordered on significance in the presence of above-median homocysteine level [2.73 (0.94-7.90)]. CONCLUSIONS: These findings suggest gene-environment and gene-gene interactions on the risk of AD in Koreans.

Kim JM, Stewart R, Shin IS, Kim SW, Yang SJ, Yoon JS. · Department of Psychiatry, Chonnam National University Medical School, Kwangju, Republic of Korea. · Int J Geriatr Psychiatry. · Pubmed #17535018 No free full text.

Abstract: BACKGROUND: Adult leg length is influenced by nutritional intake in childhood. Shorter leg length has been found to be associated with adverse health outcomes in late life, including dementia. Smaller head circumference has also been found to be associated with dementia. The independence of these two potential markers of risk for dementia has not been investigated. METHODS: Community residents aged 65 or over (n = 916) within a defined geographic area of South Korea were screened clinically for dementia and dementia subtypes. Data on anthropometric measures (head circumference and leg length), demographics (age, gender), apolipoprotein E, and early life environment (birth order, number of siblings, parental occupation, area of residence, education) were gathered. Reproductive history was also ascertained in women. RESULTS: Both smaller head circumference and shorter leg length were associated with increased age, rural residence in childhood and lower education. After adjustment for these factors, they were both independently associated with Alzheimer's disease but only in women. CONCLUSIONS: Smaller head size and shorter limb length were associated with lower early-life socio-economic status. Both factors were apparently independent markers of risk for dementia which may indicate risk factors occurring in childhood affecting both brain and skeletal development. Associations were principally present in women. Reasons for gender differences in associations require clarification but, for this population and age group, may include preferential treatment of male children.

Stewart R, White LR, Xue QL, Launer LJ. · King's College London (Institute of Psychiatry), Section of Epidemiology, England. · Arch Neurol. · Pubmed #17210816 links to  free full text

Abstract: BACKGROUND: The relationship between total cholesterol levels and dementia is unclear. OBJECTIVE: To compare the natural history of change in total cholesterol across 26 years between men who did and did not develop dementia 3 years after the last measurement. DESIGN, SETTING, AND PARTICIPANTS: In the Honolulu-Asia Aging Study, 1027 Japanese American men had total cholesterol levels assayed on 5 occasions between 1965 and 1993 and were screened for dementia on 2 occasions between 1991 and 1996. MAIN OUTCOME MEASURE: The slope of 26-year change in serum total cholesterol levels was estimated by a repeated-measures analysis and was compared between men with incident dementia (n = 56) and those without dementia (n = 971) at the end of the follow-up period. RESULTS: Cholesterol levels in men with dementia and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period. The difference in slopes was robust to adjustment for potential confounding factors, including vascular risk factors, weight change, alcohol intake, and use of lipid-lowering agents. CONCLUSION: A decline in serum total cholesterol levels may be associated with early stages in the development of dementia.

Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Yoon JS. · Department of Psychiatry, Chonnam National University Medical School, Kwangju, Republic of Korea. · Am J Geriatr Psychiatry. · Pubmed #17068317 No free full text.

Abstract: OBJECTIVE: Subjective memory complaints (SMCs) are associated with an increased incidence of dementia, but changes in SMCs have received little investigation. This study aimed to investigate the prospective association between change in self-reported memory and incident dementia in a community sample. METHOD: Korean residents aged 65+ without dementia were followed over a 2.4-year period (N = 686). SMCs were ascertained on both occasions using the Geriatric Mental State schedule. Incident dementia was ascertained at follow up, applying Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. RESULTS: Compared with those without SMCs on either occasion, dementia incidence was higher in those with persistent SMCs (present on both occasions) and transient SMCs (present at baseline but not follow up). There was no association with new onset of SMCs during follow up. The association with transient SMCs was weakened when those with cognitive impairment at baseline were excluded. CONCLUSIONS: Incident dementia is associated with memory complaints that persist or disappear but not with new complaints.

Shin IS, Stewart R, Kim JM, Kim SW, Yang SJ, Shin HY, Jung JS, Yoon JS. · Department of Psychiatry, Chonnam National University Medical School, Kwangju, Republic of Korea. · Int J Geriatr Psychiatry. · Pubmed #16250071 No free full text.

Abstract: BACKGROUND: The association between the mutant allele of mitochondrial aldehyde dehydrogenase (ALDH2*2) and Alzheimer's disease (AD) has been controversial and only so far investigated in cross-sectional studies. This study aimed to investigate the longitudinal association between ALDH2*2 and incidence of AD. METHODS: Of 592 participants aged 65 or over without dementia at baseline, 510 (86%) were re-evaluated after 2.4 years and comprised the study sample. Baseline measures included: demographic characteristics, drinking behavior, cognitive function (MMSE), clinical diagnoses of dementia and AD, and genotype (ALDH2 and apolipoprotein E). At the follow up examination, alcohol related characteristics, MMSE and clinical diagnoses of dementia and AD were reassessed. RESULTS: There were no significant associations between the ALDH2*2 and any cognitive outcomes (incidence of dementia or AD, or cognitive decline). These findings were not changed after adjustment for alcohol consumption. No interaction was found between ALDH2 and apolipoprotein E. CONCLUSIONS: ALDH2*2 does not seem to be important in the etiology of dementia.

Stewart R, Masaki K, Xue QL, Peila R, Petrovitch H, White LR, Launer LJ. · Institute of Psychiatry, London, United Kingdom. · Arch Neurol. · Pubmed #15642850 links to  free full text

Abstract: BACKGROUND: The course of weight loss associated with dementia is unclear, particularly prior to and around the onset of the clinical syndrome. OBJECTIVE: To compare the natural history of weight change from mid to late life in men with and without dementia in late life. DESIGN AND SETTING: The Honolulu-Asia Aging Study, a 32-year, prospective, population-based study of Japanese American men who had been weighed on 6 occasions between 1965 and 1999 and who had been screened for dementia 3 times between 1991 and 1999. PARTICIPANTS: Of 1890 men (aged 77-98 years), 112 with incident dementia were compared with 1778 without dementia at the sixth examination (1997-1999). MAIN OUTCOME MEASURE: Weight change up to and including the sixth examination was treated as the dependent variable and estimated using a repeated measures analysis. RESULTS: Groups with and without dementia did not differ with respect to baseline weight or change in weight from mid to late life (first 26 years' follow-up). In the late-life examinations (final 6 years), mean age- and education-adjusted weight loss was -0.22 kg/y (95% confidence intervals, -0.26 to -0.18) in participants without dementia. Men with incident dementia at the same examination had an additional yearly weight loss of -0.36 kg (95% confidence interval, -0.53 to -0.19). This was not changed substantially with adjustment for risk factors for vascular disease or functional impairment and was significant for both Alzheimer disease and vascular dementia subtypes. CONCLUSIONS: Dementia-associated weight loss begins before the onset of the clinical syndrome and accelerates by the time of diagnosis. The potential impact on prognosis should be considered in the case of elderly persons at risk for dementia.

Kim JM, Stewart R, Shin IS, Jung JS, Yoon JS. · Department of Psychiatry, College of Medicine, Chosun University, Kwangju, South Korea. · Neurobiol Aging. · Pubmed #15123334 No free full text.

Abstract: BACKGROUND: The mutant allele of mitochondrial aldehyde dehydrogenase (ALDH2(*)2) was found to be associated with Alzheimer's disease (AD) in a Japanese sample, interacting with the apolipoprotein E epsilon 4 allele (Apo E4). OBJECTIVE: In a community Korean population we sought to investigate associations between ALDH2 genotypes and the following outcomes: cognitive impairment, previous cognitive decline, dementia and AD. METHODS: Six hundred ninety community residents aged 65 or over were assessed for demographic characteristics, drinking behaviour, cognitive function, clinical diagnoses of dementia and AD, physical health status, and genotype (ALDH2 and Apo E). RESULTS: There were no significant associations between the ALDH2(*)2 and any cognitive outcome, before or after adjustment for alcohol-related characteristics. These findings were consistent both in the non-drinkers and drinkers. Interaction between ALDH2 and Apo E was only found for one outcome (previous cognitive decline) at borderline levels of significance (P=0.058). CONCLUSIONS: Overall, these findings in a community population did not support a substantial role for ALDH2 genotype in the aetiology of dementia.

Stewart R, Russ C, Richards M, Brayne C, Lovestone S, Mann A. · Section of Old Age Psychiatry, Institute of Psychiatry, London, UK. · Dement Geriatr Cogn Disord. · Pubmed #11351136 No free full text.

Abstract: A reduced risk of Alzheimer's disease (AD) associated with the apolipoprotein E (APOE) epsilon4 allele is reported in populations of African origin. In order to clarify possible reasons for this, we examined the association between APOE genotype and early cognitive impairment in a community-based African Caribbean UK population aged 55-75 years. APOE genotype was available for 202 participants, 57 (28%) of whom were classified as having relative cognitive impairment on a battery of neuropsychological tests. Cognitive impairment was negatively associated with epsilon2 and positively but more weakly associated with epsilon4. Effects of both alleles increased markedly after age 70. The effect of epsilon4 was increased in combination with hypertension, diabetes or lower educational attainment, but these factors did not influence epsilon2 effects. Cholesterol and triglyceride levels partially explained effects of epsilon2, but did not account for those of epsilon4. A reduced association between epsilon4 and later AD in populations of African origin is unlikely to be explained by reduced cognitive effects or by differential mortality. However, it may be accounted for by vascular comorbidity. The different patterns of association between epsilon2 and epsilon4 alleles suggest different pathways of effect.

Stewart R. · No affiliation provided · BMJ. · Pubmed #16410593 links to  free full text

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Stewart R. · No affiliation provided · Neurology. · Pubmed #11739854 No free full text.

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Stewart R. · No affiliation provided · Br J Psychiatry. · Pubmed #11581121 links to  free full text

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Stewart R. · No affiliation provided · Lancet. · Pubmed #11458939 No free full text.

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Stewart R. · No affiliation provided · BMJ. · Pubmed #11403062 No free full text.

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