Marinesco bodies and substantia nigra neuron density in Parkinson's disease.

AIM: Marinesco bodies (MB) are intranuclear inclusions in pigmented neurons of the substantia nigra (SN). While rare in children, frequency increases with normal ageing and is high in Alzheimer's disease, dementia with Lewy bodies and other neurodegenerative disorders. Coinciding with the age-related rise in MB frequency is initiation of cell death among SN neurons. Whether MB have a role in this process is unknown. Our aim is to examine the association of MB with SN neuron density in Parkinson's disease (PD) in the Honolulu-Asia Aging Study. METHODS: Data on MB and neuron density were measured in SN transverse sections in 131 autopsied men aged 73-99 years at the time of death from 1992 to 2007. RESULTS: Marinesco body frequency was low in the presence vs. absence of PD (2.3% vs. 6.6%, P < 0.001). After PD onset, MB frequency declined as duration of PD increased (P = 0.006). Similar patterns were observed for SN neuron density. When MB frequency was low, neuron density was noticeably reduced in the SN ventrolateral quadrant, the region most vulnerable to PD neurodegeneration. Low MB frequency was unique to PD as its high frequency in non-PD cases was unrelated to parkinsonian signs and incidental Lewy bodies. Frequency was high in the presence of Alzheimer's disease and apolipoprotein ε4 alleles. CONCLUSIONS: While findings confirm that MB frequency is low in PD, declines in MB frequency continue with PD duration. The extent to which MB have a distinct relationship with PD warrants clarification. Further studies of MB could be important in understanding PD processes.

Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy.

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's disease.

BACKGROUND AND PURPOSE: In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. METHODS: Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04). CONCLUSION: In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.

Association of fibrinogen with Parkinson disease in elderly Japanese-American men: a prospective study.

BACKGROUND: The purpose of this prospective study was to examine whether fibrinogen level is associated with Parkinson disease (PD) for both prevalent and incident cases. METHODS: The Honolulu Asia-Aging Study is a longitudinal study of Japanese-American men based on the Honolulu Heart Study birth cohort. The original cohort consisted of 8,006 participants with selective service records who were living on the island of Oahu, Hawaii, in 1965. For this analysis, baseline was defined as the 1991-1993 examination (n = 3,845) when men were aged 71-93 years old. Multivariate logistic regression and Cox proportional hazards models were used, adjusting for potential confounders. RESULTS: We identified 61 prevalent cases and 61 incident cases of PD during the follow-up. High fibrinogen level (presence in the top quintile) was associated with higher frequency of PD for both prevalent (OR = 2.07, 95% CI = 1.10-3.88, p = 0.024) and incident cases (HR = 3.05, 95% CI = 1.34-6.97, p = 0.008) among men aged 76-93 years, after adjusting for age, smoking, and low-density lipoprotein cholesterol. CONCLUSIONS: These results suggest high fibrinogen level is associated with increased risk of PD among men over 75 years.

Prevalence of Parkinson's disease across North America.

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

Occupational and other risk factors for hand-grip strength: the Honolulu-Asia Aging Study.

BACKGROUND: In certain occupations, including farm work, workers are exposed to hazardous substances, some of which are known to be toxic to the nervous system and may adversely affect muscle strength. Measurement of hand-grip strength may be useful for detecting neurotoxic exposure. METHODS: The authors studied 3522 participants of the Honolulu Heart Program and the Honolulu-Asia Aging Study to determine whether occupational exposures to pesticides, solvents, and metals assessed at exam I (1965-68) are associated with hand-grip strength at exam IV (1991-93) and change in hand-grip strength over 25 years. Correlation, analysis of variance and covariance, and linear regression were used to evaluate the associations. RESULTS: At exam IV, participants ranged in age from 71-93 years; mean hand-grip strength was 39.6 kg at exam I and 30.3 kg at exam IV. Over 25 years, the decline in hand-grip strength was an average of 8-9 kg for all exposures. Hand-grip strength was inversely associated with age and glucose but directly associated with cognitive function, BMI, and haemoglobin level. No other exposures were associated with hand-grip strength. CONCLUSION: This study did not provide evidence that occupational exposure to pesticides, solvents, and metals adversely affected hand-grip strength in this population, but confirmed other important associations with hand-grip strength.

Effects of walking on coronary heart disease in elderly men: the Honolulu Heart Program.

BACKGROUND: Effects of walking on the risk of coronary heart disease morbidity and mortality have not been identified in the elderly. The purpose of this study was to determine whether walking is associated with a reduced risk of coronary heart disease in a sample of elderly men. METHODS AND RESULTS: For this study, distance walked (mile/d) was examined at a baseline examination that occurred from 1991 to 1993 in the Honolulu Heart Program. Incident coronary heart disease from all causes was observed over a 2- to 4-year follow-up period. Subjects followed up were 2678 physically capable elderly men aged 71 to 93 years. During the course of follow-up, 109 men developed coronary heart disease. Men who walked <0.25 mile/d had a 2-fold increased risk of coronary heart disease versus those who walked >1. 5 mile/d (5.1% versus 2.5%; P<0.01). Men who walked 0.25 to 1.5 mile/d were also at a significantly higher risk of coronary heart disease than men who walked longer distances (4.5% versus 2.5%; P<0. 05). Adjustment for age and other risk factors failed to alter these findings. CONCLUSIONS: Findings from the Honolulu Heart Program, which targeted physically capable elderly men, suggest that the risk of coronary heart disease is reduced with increases in distance walked. Combined with evidence that suggests that an active lifestyle reduces the risk of cardiovascular disease in younger and more diverse groups, this suggests that important health benefits could be derived by encouraging the elderly to walk.

Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study.

Cardiovascular risk factors often cluster into a metabolic syndrome that may increase the risk of dementia. The objective of the present study was to assess the long-term association between clustered metabolic cardiovascular risk factors measured at middle age and the risk of dementia in old age. This prospective cohort study of cardiovascular disease was started in 1965 and was extended to a study of dementia in 1991. The subjects were Japanese-American men with an average age of 52.7+/-4.7 (mean+/-SD) years at baseline. Dementia was diagnosed in 215 men, according to international criteria, and was based on a clinical examination, neuropsychological testing, and an informant interview. The z scores were calculated for 7 risk factors (random postload glucose, diastolic and systolic blood pressures, body mass index, subscapular skinfold thickness, random triglycerides, and total cholesterol). The relative risk (RR [95% CI]) of dementia (subtypes) per 1 SD increase in the sum of the z scores was assessed after adjustment for age, education, occupation, alcohol consumption, cigarette smoking, and years of childhood lived in Japan. The z-score sum was higher in demented subjects than in nondemented subjects, indicating a higher risk factor burden (0.74 versus -0.06, respectively; P=0. 008). Per SD increase in the z-score sum, the risk of dementia was increased by 5% (RR 1.05, 95% CI 1.02 to 1.09). The z-score sum was specifically associated with vascular dementia (RR 1.11, 95% CI 1.05 to 1.18) but not with Alzheimer's disease (RR 1.00, 95% CI 0.94 to 1.05). Clustering of metabolic cardiovascular risk factors increases the risk of dementia (mainly, dementia of vascular origin).

beta(2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the honolulu heart program.

BACKGROUND: It has been hypothesized that immunoreactivity to beta(2)-glycoprotein 1 (beta2GP1)-dependent anticardiolipin antibody (aCL), but not beta2GP1-independent aCL, is associated with increased risk of ischemic stroke and myocardial infarction (MI). METHODS: We performed a nested case-control study examining aCL as a risk factor for ischemic stroke and MI by using stored frozen sera obtained from subjects enrolled in the Honolulu Heart Program and followed for up for 20 years. We measured beta2GP1-dependent and beta2GP1-independent aCL and anti-beta2GP1 immunoreactivity in 259 men who developed an ischemic stroke, in 374 men who developed an MI, and in a control group of 1360 men who remained free of both conditions. RESULTS: Only beta2GP1-dependent aCL of the IgG class was significantly associated with both incident ischemic stroke and MI. This association was attenuated in the last 5 years of the 20-year follow-up. For stroke, the risk factor-adjusted relative odds for men with a positive versus a negative beta2GP1-dependent aCL of the IgG class were 2.2 (95% CI 1.5 to 3.4) at 15 years and 1.5 (95% CI 1.0 to 2.3) at 20 years. For MI, the adjusted relative odds were 1.8 (95% CI 1.2 to 2.6) at 15 years and 1.5 (95% CI 1.1 to 2.1) at 20 years. CONCLUSIONS: These data suggest that aCL IgG, particularly the beta2GP1-dependent variety, is an important predictor of future stroke and MI in men.

Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment: the Honolulu-Asia aging study.

BACKGROUND AND PURPOSE: The aim of this study was to explore the joint effect of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life. METHODS: The study includes 3605 surviving members of the cohort of the Japanese-American men followed prospectively over 26 years (1965-1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No epsilon4, as the reference category; normal SBP/epsilon4; high SBP/no epsilon4; high SBP/epsilon4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening Instrument (CASI) test. RESULTS: After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI <74) compared with good cognitive function (CASI >/=82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for the high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4.5) for those with both risk factors. CONCLUSIONS: The results suggest that midlife high SBP has a stronger adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.

Midlife blood pressure and dementia: the Honolulu-Asia aging study.

We studied the association of mid-life blood pressure to late age dementia, specifically Alzheimer's disease and vascular dementia. Data are from the cohort of 3703 Japanese-American men who were followed in the Honolulu Heart Program (HHP;1965-1971), and subsequently re-examined in 1991 for dementia. We assessed the risk (odds ratio (95% CI)) for dementia associated with categories of systolic (SBP) and diastolic blood pressure (DBP), stratified by never/ever treatment with anti-hypertensive medications, and adjusting for age, education, apolipoprotein epsilon allele, smoking and alcohol intake. Among those never treated (57% sample), the risk for dementia was OR 95% CI 3.8 (1.6-8.7) for DBP of 90-94 mm Hg, and 4. 3 (1.7-10.8) for DBP of 95 mmHg and over compared to those with DBP of 80 to 89 mm Hg. Compared to those with SBP of 110 to 139 mm Hg, the risk for dementia was 4.8 (2.0-11.0) in those with SBP 160 mm Hg and higher. Blood pressure was not associated with the risk for dementia in treated men. These results were consistent for Alzheimer's disease and vascular dementia. This study suggests elevated levels of blood pressure in middle age can increase the risk for late age dementia in men never treated with anti-hypertensive medication.

Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study.

Midlife hypertension is associated with later development of cognitive impairment, vascular dementia (VsD), and possibly Alzheimer's disease (AD). Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure (BP), however, to our knowledge there have been no prospective investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD. We investigated the relationship of BP level in midlife to development of neurofibrillary tangles (NFT), neuritic plaques (NP), and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study (HHP/HAAS) cohort. The HHP/HAAS is a population-based, longitudinal study of cognitive function and dementia with 36 years of follow-up. Neocortical and hippocampal NFT and NP were counted per mm(2), and fixed brain weight was measured for 243 decedents. Elevated systolic BP, (> or =160 mm Hg) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus. Diastolic BP elevation, (> or =95 mm Hg) was associated with greater numbers of NFT in hippocampus. Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions, there is a direct relationship with brain atrophy, NP and NFT.

Posterior cortical atrophy. Neuropathologic correlations.

OBJECTIVE: A subgroup of patients with progressive dementia has been reported with a marked predominance of symptoms attributed to the dysfunction of the posterior parieto-occipital cortex. These cases have been referred to as posterior cortical atrophy. The objective of this study was to determine whether posterior cortical atrophy is associated with distinct, uniform neuropathologic findings. DESIGN: Three individuals with progressive dementia that began with higher visual dysfunction (posterior cortical atrophy) were followed up to definitive neuropathologic diagnosis. RESULTS: Three separate neuropathologic entities were discovered: subcortical gliosis, Alzheimer's disease, and Creutzfeldt-Jakob disease. CONCLUSION: Posterior cortical atrophy is a clinically homogeneous but pathologically heterogeneous syndrome.

Cigarette smoking and protection from Parkinson's disease: false association or etiologic clue?

We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue.

Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study.

OBJECTIVE: To investigate the relationship between cerebral amyloid angiopathy (CAA), dementia, and cognitive function in an autopsy sample of 211 Japanese-American men from the population-based Honolulu-Asia Aging Study. METHODS: Starting in 1991, participants were assessed with the Cognitive Abilities Screening Instrument (CASI) and diagnosed with dementia (including subtype) based on published criteria. At autopsy, neuropathologists blinded to clinical data examined brains for neurofibrillary tangles (NFT), neuritic plaques (NP), and a number of vascular pathologies, including CAA. CAA was detected by immunostaining for betaA4 amyloid in parenchymal vessels in the neocortex and semiquantitatively rated. Linear regression models were used to examine the association of CASI score, dementia subtype, and CAA controlling for age at death, time between CASI administration and death, education, NP and NFT counts, infarcts, hemorrhage, and APOE genotype. RESULTS: A total of 44.1% of subjects had CAA in at least one neocortical area. The presence of CAA was associated with higher mean NFT and NP counts and having at least one APOE-epsilon4 allele. The interaction between CAA and AD on the adjusted mean CASI score was significant; compared with nondemented men without CAA, the CASI score was 16.6% lower in men with AD and no CAA and 45.9% lower in men with AD plus CAA. CONCLUSIONS: CAA may contribute to the clinical presentation of dementia by interacting with other neuronal pathologies, leading to more severe cognitive impairment in men with both CAA and AD compared with men with only AD or CAA.

Cholesterol and neuropathologic markers of AD: a population-based autopsy study.

OBJECTIVE: To examine the association of plasma cholesterol (total and high-density [HDL] and low-density lipoprotein) levels with neuritic plaques (NP) and neurofibrillary tangles (NFT) in a population-based autopsy series of 218 Japanese American men followed as a part of the Honolulu-Asia Aging Study. METHODS: Cholesterol levels were measured in late life (average age at death 84.6 years) in all subjects (n = 218) and in midlife (20 years before late life) in a subsample (n = 89); for the analyses, levels were categorized into quintiles, with the lowest quintile serving as the reference. Tissue from four areas of neocortex and two areas of hippocampus was prepared with Bielschowsky silver-stained sections and evaluated by one of three neuropathologists who were blinded to clinical information. Diffuse and neuritic plaques and NFT were counted in field areas standardized to 1 mm(2). Fields were selected from areas with the highest numbers of lesions, and the field with the highest count was taken to represent the brain area. RESULTS: After adjusting for age at death, education, APOE allele, dementia, neuropathologic infarction, and blood pressure, a strong linear association was found for increasing late-life HDL cholesterol (HDL-C) levels and an increasing number of neocortical NP (5th versus 1st quintile: count ratio [95% CI] 2.30 [1.05 to 5.06]) and hippocampal (2.63 [1.25 to 5.50]) and neocortical (4.20 [1.73 to 10.16]) NFT. Trends were similar for the midlife HDL-C levels. CONCLUSIONS: The constituents of HDL-C may play a role in the formation of AD pathology, and these processes are reflected in peripheral measures.

Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake.

A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods. All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence. Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence.

Epidemiologic observations on Parkinson's disease: incidence and mortality in a prospective study of middle-aged men.

We determined age-specific and age-adjusted incidence rates and mortality rates of idiopathic Parkinson's disease (PD) in a cohort of men followed for 29 years. Since enrollment in 1965, the Honolulu Heart Study has followed 8,006 American men of Japanese or Okinawan ancestry. Rescreening of the entire cohort, completed in 1994, included attempts to detect all prevalent and incident cases of PD, parkinsonism, and related conditions. PD incidence rates and age-incidence patterns were similar to rates previously published for Caucasian men in Europe and the United States, and were higher than incidence rates published for Asian men living in Asian nations. Prevalence patterns appeared to correspond more closely to patterns observed in developed nations than in Asian nations. PD was associated with markedly increased mortality that appeared to result from effects of both absolute age and disease duration. There was no firm evidence for differences in birth cohort risks of PD. These data may have implications for maturational and environmental theories of PD etiology.

Association of vitamin E and C supplement use with cognitive function and dementia in elderly men.

OBJECTIVE: To determine whether use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning. METHODS: The Honolulu-Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study were obtained from a subsample of the cohort interviewed in 1982, and from the entire cohort from a mailed questionnaire in 1988 and the dementia prevalence survey in 1991 to 1993. The subjects included 3,385 men, age 71 to 93 years, whose use of vitamin E and C supplements had been ascertained previously. Cognitive performance was assessed with the Cognitive Abilities Screening Instrument, and subjects were stratified into four groups: low, low normal, mid normal, and high normal. For the dementia analyses, subjects were divided into five mutually exclusive groups: AD (n = 47), vascular dementia (n = 35), mixed/other types of dementia (n = 50), low cognitive test scorers without diagnosed dementia (n = 254), and cognitively intact (n = 2,999; reference). RESULTS: In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements in 1988 (odds ratio [OR], 0.12; 95% CI, 0.02 to 0.88). They were also protected against mixed/other dementia (OR, 0.31; 95% CI, 0.11 to 0.89). No protective effect was found for Alzheimer's dementia (OR, 1.81; 95% CI, 0.91 to 3.62). Among those without dementia, use of either vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination (OR, 1.25; 95% CI, 1.04 to 1.50), and use of both vitamin E and C together had borderline significance (OR, 1.18; 95% CI, 0.995 to 1.39). CONCLUSIONS: These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life.

APOE-epsilon4 predicts incident AD in Japanese-American men: the honolulu-asia aging study.

The authors assessed the 3-year incidence of dementia, including subtypes, in 2,603 Japanese-American men 71 to 93 years of age who were dementia free at baseline. There were 137 new cases of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised, including 51 with a primary diagnosis of AD. The rates for all subtypes increased with age. Men with an APOE4 allele had a significantly increased risk of AD of 2.39 (95% CI, 1.07, 5.31), after adjusting for age and education. There was no significant relationship of APOE4 with other subtypes of dementia.