Biomedical subjects

G Webster Ross

Publications and source records attributed to G Webster Ross.

At least 19 recordsLinked to original sources

PubMed2006

Occupational exposures and movement abnormalities among Japanese-American men: the Honolulu-Asia Aging Study.

OBJECTIVE: The authors analyzed data on 1,049 men aged 71-93 years (excluding those with prevalent Parkinson's disease and stroke) from the Honolulu Heart Program (1965-1968) and the Honolulu-Asia Aging Study (1991-1999) to determine whether occupational exposures to pesticides, solvents, metals, manganese, and mercury during middle age were associated with 14 movement abnormalities 25 years later. METHODS: Analyses of variance and multivariate logistic regression were used to assess associations of interest. RESULTS: After adjustment for age, BMI, cognitive functioning, smoking, alcohol drinking, education, and physical activity, there was a positive association between abnormal 'facial expression' and the highest exposure to metals [odds ratio (OR) = 2.62; 95% confidence interval (CI) = 1.35-5.11; trend, p = 0.02], and the highest exposure to mercury (OR = 1.91; 95% CI = 1.04-3.49; trend, p = 0.03). Age was positively associated with all movement abnormalities, and cognitive function, body mass index and physical activity were inversely associated with most movement abnormalities. CONCLUSION: Higher exposure to any metal, and specifically mercury, was associated with abnormal facial expression.

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PubMed2006

Endogenous sex hormones, cognitive decline, and future dementia in old men.

OBJECTIVE: To estimate the association of endogenous levels of bioavailable testosterone and estradiol with risk for cognitive decline and dementia in old men. METHODS: Within the population-based, prospective Honolulu-Asia Aging Study, 2,974 men, aged 71 to 93 years, without dementia were reexamined 3 times over an average of 6 years for development of dementia and cognitive decline. Cognitive decline was measured with the Cognitive Abilities Screening Instrument. Incident dementia was diagnosed according to standard criteria. A total of 134 men experienced development of Alzheimer's disease (AD; including 40 cases with contributing cerebrovascular disease) and 44 experienced development of vascular dementia. RESULTS: Adjusting for age and other covariates, testosterone was not associated with risk for dementia (using Cox regression analyses) or cognitive decline (using random coefficient analyses). However, higher levels of estradiol were associated with risk for AD (hazard ratio per standard deviation increase, 1.25; 95% confidence interval, 1.05-1.47) and AD with cerebrovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.38). Also, compared with the lowest tertile of estradiol, men in the middle and highest tertile of estradiol had 0.24 and 0.28 points lower Cognitive Abilities Screening Instrument scores, respectively, for each year increase in age. INTERPRETATION: In old men, endogenous testosterone levels are not associated with risk for cognitive decline and AD, whereas higher estrogen levels increase risk for cognitive decline and AD.

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PubMed2006

Association of olfactory dysfunction with incidental Lewy bodies.

Olfactory dysfunction is found in early Parkinson's disease (PD) and in asymptomatic relatives of PD patients. Incidental Lewy bodies (ILB), the presence of Lewy bodies in the brains of deceased individuals without a history of PD or dementia during life, are thought to represent a presymptomatic stage of PD. If olfactory dysfunction were associated with the presence of ILB, this would suggest that olfactory deficits may precede clinical PD. The purpose of this study was to determine the association of olfactory dysfunction during late life with ILB in the substantia nigra or locus ceruleus. Olfaction was assessed during the 1991-1994 and 1994-1996 examinations of elderly Japanese-American men participating in the longitudinal Honolulu-Asia Aging Study. Among those who later died and underwent a standardized postmortem examination, brains were examined for Lewy bodies in the substantia nigra and the locus ceruleus with hematoxylin and eosin stain. Lewy bodies in the brains of individuals without clinical PD or dementia were classified as ILB. There were 164 autopsied men without clinical PD or dementia who had olfaction testing during one of the examinations. Seventeen had ILB. The age-adjusted percent of brains with ILB increased from 1.8% in the highest tertile of odor identification to 11.9% in the mid-tertile to 17.4% in the lowest tertile (P = 0.019 in test for trend). Age-adjusted relative odds of ILB for the lowest versus the highest tertile was 11.0 (P = 0.02). Olfactory dysfunction is associated with ILB. If incidental Lewy bodies represent presymptomatic stage of PD, olfactory testing may be a useful screening tool to identify those at high risk for developing PD.

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PubMed2005

Midlife pulse pressure and incidence of dementia: the Honolulu-Asia Aging Study.

BACKGROUND AND PURPOSE: Previous studies have shown that midlife systolic blood pressure (SBP) predicts late-life cognitive decline and incident dementia. This study explores whether this association is attributable to the pulsatile, ie, pulse pressure (PP), or the nonpulsatile component of blood pressure (BP). METHODS: Data are from the Honolulu-Asia Aging Study, a community-based study of Japanese American men. Midlife BP was measured in 1971 to 1974 and dementia assessment was conducted in late-life. The 2505 men who were dementia free in 1991 and had complete follow-up data were re-examined for incident dementia in 1994 to 1996 and 1997 to 1999. Their age ranged from 71 to 93 years. Survival analysis with age as the time scale was performed to estimate the risk (hazard ratio [HR] and 95% CI) for incident dementia associated with mid- and late-life tertiles of PP and mean arterial BP, as well as SBP and diastolic BP categories. RESULTS: Over a mean of 5.1 years of follow-up, 189 cases (7.5%) of incident Alzheimer disease or vascular dementia were identified. After adjustment for cerebrovascular risk factors, dementia was significantly associated with SBP (HR 1.77; 95% CI, 1.10 to 2.84, for SBP > or =140 mm Hg compared with SBP <120 mm Hg), but not with PP tertiles. Limiting the analysis to those never treated with antihypertensives, high levels of all 4 BP components were significantly associated with dementia. In models with 2 BP components, only SBP remained significant in both the total sample and the never-treated subgroup (HR 2.29; 95% CI, 1.23 to 4.25, for SBP > or =140 mm Hg in total sample), whereas PP was not significantly associated with the risk for dementia. CONCLUSIONS: Midlife PP is not independently associated with dementia incidence. Midlife SBP is the strongest BP component predicting incident dementia.

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PubMed2005

AD lesions and infarcts in demented and non-demented Japanese-American men.

Neocortical neuritic plaques and neurofibrillary tangles are hallmark neuropathological lesions of dementia. Concomitant cerebrovascular lesions increase dementia severity in patients meeting neuropathological criteria for Alzheimer's disease and contribute to cognitive impairment in persons with mild entorhinal Alzheimer lesions. This study investigates whether individuals with sparse neocortical neuritic plaques experience increased odds of crossing the threshold to clinical dementia when they have coexistent cerebrovascular lesions. Dementia examinations were given to 3,734 men during the 1991-1993 Honolulu-Asia Aging Study examination and to 2,603 men during the 1994-1996 examination. Lesion quantification was done without clinical data. Among 333 autopsied men, 120 had dementia, 115 had marginal results, and 98 had normal cognition. In men with neurofibrillary tangles, dementia frequency increased with increasing neuritic plaque density, and increased further in the presence of cerebrovascular lesions. The association was strongest in men with sparse neuritic plaques (1-3/mm(2)) where dementia frequency more than doubled with coexistent cerebrovascular lesions (45 vs 20%). Among all dementia cases, 24% were linked to cerebrovascular lesions. Findings suggest cerebrovascular lesions are associated with a marked excess of dementia in cases with low neuritic plaque frequency. Prevention of cerebrovascular lesions may be critically important in preserving late-life cognitive function.

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PubMed2005

Smell identification ability in twin pairs discordant for Parkinson's disease.

Olfactory dysfunction has been proposed to be a sign that may precede the motor features of Parkinson's disease (PD). To determine whether smell identification deficits predict subsequent PD, we studied smell identification ability using the University of Pennsylvania Smell Identification Test (UPSIT) in 62 members of male twin pairs discordant for PD at baseline. Smell identification ability was reduced at baseline in the twins with PD compared to their unaffected brothers (23 vs. 31 of 40; P = 0.001). UPSIT scores were not reduced in the twins without PD when compared to age- and gender-specific normal values. After a mean interval of 7.3 years, 28 unaffected twins were still alive and 19 agreed to a second evaluation. Two had newly developed PD. Neither twin had impaired smell identification at baseline. The average decline in UPSIT percentile scores in these 2 twins was greater than in the 17 twins who did not develop PD (-68% vs. -24%; P = 0.01). In subjects who did not meet Core Assessment Program for Intracerebral Transplantations diagnostic criteria for PD at baseline, the presence of cardinal signs of parkinsonism was not associated with lower baseline UPSIT scores nor with a subsequent decline. Smell identification ability may not be a sensitive indicator of future PD 7 or more years before the development of motor signs, even in a theoretically at-risk population.

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PubMed2005

Cognitive deficits 3 to 6 years before dementia onset in a population sample: the Honolulu-Asia aging study.

OBJECTIVE: To determine the type of cognitive deficits occurring 3 to 6 years before onset of dementia in a population sample. DESIGN: A prospective study in which cognitive deficits in participants who had incident dementia at the 6-year follow-up were examined at baseline and 3 years. SETTING: Honolulu, Hawaii. PARTICIPANTS: Three thousand seven hundred thirty-four Japanese-American men aged 71 to 93 at baseline. At the 6-year follow-up, there were 52 incident cases of dementia, and 1,559 controls. MEASUREMENTS: The Cognitive Abilities Screening Instrument (CASI) and a questionnaire on subjective memory problems were administered at baseline. Dementia was assessed at baseline and at 3-year and 6-year follow-ups. RESULTS: Subjects who had incident dementia at 6-year follow-up, had showed deficits 3 to 6 years earlier in the CASI domain of episodic memory and in the questionnaire covering subjective memory problems. Up to 3 years before onset, there was worsening of the episodic memory deficit from baseline and new deficits in language, verbal fluency, and orientation. CONCLUSION: Cognitive deficits and awareness of memory problems are frequently present several years before dementia onset. The predictive value of these deficits is not large enough to allow earlier diagnosis of dementia, but information about such deficits may be useful as criteria for mild cognitive impairment.

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PubMed2005

Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia Aging Study.

In this study, we compare neuropathological findings at autopsy with clinical dementia diagnoses, such as Alzheimer's disease and vascular dementia. Participants consisted of 363 aged Japanese-American men from the Honolulu-Asia Aging Study. Results indicated that the correspondence between clinical and neuropathologic diagnosis was not great, with 56% of patients diagnosed with probable or possible Alzheimer's disease during life but with only 19% having neuritic plaques and/or neurofibrillary tangles as the sole or dominant dementia-related lesions in the brain at autopsy. Although 16% of cases were attributed to mixed causes during life, almost 40% were found to have significant mixtures of dementia-related lesions at autopsy. Finally, both Alzheimer's disease and non-Alzheimer's disease neuropathologic lesions contributed independently to the explanation of variance on a test of overall cognitive performance. The results suggest that clinical diagnosis of dementia made during life may fail to reflect the pathogenic complexity of this condition in very elderly persons.

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PubMed2004

Walking and dementia in physically capable elderly men.

CONTEXT: Evidence suggests that physical activity may be related to the clinical expression of dementia. Whether the association includes low-intensity activity such as walking is not known. OBJECTIVE: To examine the association between walking and future risk of dementia in older men. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Distance walked per day was assessed from 1991 to 1993 in 2257 physically capable men aged 71 to 93 years in the Honolulu-Asia Aging Study. Follow-up for incident dementia was based on neurological assessment at 2 repeat examinations (1994-1996 and 1997-1999). MAIN OUTCOME MEASURES: Overall dementia, Alzheimer disease, and vascular dementia. RESULTS: During the course of follow-up, 158 cases of dementia were identified (15.6/1000 person-years). After adjusting for age, men who walked the least (<0.25 mile/d) experienced a 1.8-fold excess risk of dementia compared with those who walked more than 2 mile/d (17.8 vs 10.3/1000 person-years; relative hazard [RH], 1.77; 95% confidence interval [CI], 1.04-3.01). Compared with men who walked the most (>2 mile/d), an excess risk of dementia was also observed in those who walked 0.25 to 1 mile/d (17.6 vs 10.3/1000 person-years; RH, 1.71; 95% CI, 1.02-2.86). These associations persisted after accounting for other factors, including the possibility that limited amounts of walking could be the result of a decline in physical function due to preclinical dementia. CONCLUSIONS: Findings suggest that walking is associated with a reduced risk of dementia. Promoting active lifestyles in physically capable men could help late-life cognitive function.

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PubMed2004

High density lipoprotein cholesterol and the risk of stroke in elderly men: the Honolulu heart program.

High density lipoprotein (HDL) cholesterol has been inversely associated with coronary heart disease. Associations with stroke are less clear, particularly among the elderly. In this study, the authors examined the relation between HDL cholesterol levels and the risk of stroke in elderly men. Levels of HDL cholesterol were measured in 2,444 Honolulu Heart Program men aged 71-93 years at the 1991-1993 examinations. The participants, who were free of prevalent stroke, coronary heart disease, and cancer at baseline, were followed to the end of 1998 for thromboembolic and hemorrhagic stroke. While HDL cholesterol was unrelated to hemorrhagic events, incidence of thromboembolic stroke declined consistently with increasing HDL cholesterol level (p = 0.003). There was a nearly threefold excess of thromboembolic stroke in men with low HDL cholesterol levels (<1.0 mmol/liter (<40 mg/dl)) compared with men with high levels (> or =1.6 mmol/liter (> or =60 mg/dl)) (10.6/1,000 person-years vs. 3.6/1,000 person-years; p = 0.001). Adjustment for other risk factors had little effect on these findings, although associations appeared strongest in elderly men with "desirable" total cholesterol levels, hypertension, or diabetes mellitus. These findings suggest that HDL cholesterol level is inversely related to the risk of thromboembolic stroke in elderly men. Whether HDL cholesterol alters the effect of other factors on stroke risk in elderly men warrants further study.

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PubMed2004

Parkinsonian signs and substantia nigra neuron density in decendents elders without PD.

Substantia nigra (SN) neurons were counted on single, transverse caudal midbrain sections from 217 male participants in the Honolulu-Asia Aging Study, aged 74-97 years at death. Quadrants areas within the SN were determined with a planimeter and neuronal density was expressed as neurons/mm(2) for 10 Parkinson's disease (PD) cases, 29 incidental Lewy body cases, and 178 controls with neither condition. Mean densities in all quadrants were significantly lower in the PD group compared with the other groups (p = 0.006). This relationship was strongest in the ventrolateral quadrant. In a subgroup of 50 controls who were examined with the Unified Parkinson's Disease Rating Scale an average of 2.1 years prior to death, there was an association of stooped posture (p = 0.009), postural instability (p = 0.013), body bradykinesia (p = 0.048), and gait disturbance (p = 0.05) with neuron density in the dorsolateral quadrant; and impaired speech (p = 0.014), abnormal facial expression (p = 0.022), and difficulty rising from a chair (p = 0.032) with neuron density in the dorsomedial quadrant. There was a significant association of increasing number of signs present with decreasing neuron density in both quadrants (p = 0.001 for trend). Low SN neuron density may be the basis for parkinsonian signs in the elderly without PD.

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PubMed2004

Associations of cortical astrogliosis with cognitive performance and dementia status.

We examined 204 decedents of the autopsy component of the Honolulu-Asia Aging Study, a longitudinal cohort study, who had been clinically assessed for dementia. A sensitive ELISA technique was used to quantify glial fibrillary acidic protein (GFAP), a marker for astrogliosis, in four specific cortical brain regions and assess associations between GFAP and 1) a measure of cognitive function, 2) several clinical dementia conditions, and 3) neuritic plaque (NP) and neurofibrillary tangle (NFT) formation. Cognitive function was inversely associated with GFAP in the occipital, parietal and temporal lobes, but not in the frontal lobe. This relationship remained significant when the contribution of NP and NFT counts was removed. Further, compared to brain samples from non-demented individuals, significantly greater GFAP levels were found in samples from individuals diagnosed with Alzheimer's disease, mixed dementia, and vascular mediated dementia. Because elevated levels of GFAP reflect astroglial responses to even subtle forms of neural damage, our data indicate that increments in GFAP may provide independent, supporting evidence for the damage underlying dementia, even in the absence of other evidence of neuropathology such as the presence of NPs or NFTs. Our findings underscore the need to look beyond standard neuropathological measures putatively linked to specific neuropathological conditions in efforts to identify common cellular and molecular processes that contribute to dementia.

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PubMed2003

Environmental, life-style, and physical precursors of clinical Parkinson's disease: recent findings from the Honolulu-Asia Aging Study.

BACKGROUND: Increased westernization with Japanese migration to the U. S. in the early 20(th) century is thought to have altered the risk of cardiovascular disease. Whether similar effects include changes in the risk of Parkinson's disease (PD) is not clear. This report describes the relations between environmental, life-style, and physical attributes and the incidence of PD that have been observed in the Honolulu-Asia Aging Study. METHODS: Beginning in 1965, environmental, life-style, and physical attributes were recorded at selected examinations in a cohort of 8,006 Japanese-American men. Subjects were followed for clinical PD. FINDINGS: During 30 years of follow- up, PD was observed in 137 men. Overall incidence (7.1/10,000 person-years) was generally higher than in Asia and similar to rates observed in Europe and the U. S. Precursors of PD included constipation, adiposity, years worked on a sugar or pineapple plantation, years of exposure to pesticides, and exposure to sugar cane processing. Factors showing an inverse association with PD included coffee intake and cigarette smoking. Among dietary factors, carbohydrates increased the risk of PD while the intake of polyunsaturated fats appeared protective. Total caloric intake, saturated and monounsaturated fats, protein, niacin, riboflavin, beta-carotene, vitamins A, B, and C, dietary cholesterol, cobalamin, alpha-tocopherol, and pantothenic acid showed no clear relation with clinical PD. INTERPRETATION: Findings suggest that several environmental, life-style, and physical attributes appear to be precursors of PD. Whether patterns of precursors can be used to identify individuals at high risk of future PD or can broaden the scope of early interventions or recruitment into neuroprotective trials warrants further study.

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PubMed2003

Age-related changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke.

We examined the changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke as they may occur with age. Findings were based on repeated risk factor measurements at four examinations over a 26-year period in 7589 men in the Honolulu Heart Program. After each examination, 6 years of follow-up were available to assess risk factor effects on the incidence of stroke over a broad range of ages (45-93 years). As compared with normotensive men, the risk of thromboembolic stroke in the presence of hypertension declined from a 7-fold excess in men aged 45 to 54 years to a 1.4-fold excess in men aged > or =75 (P<.001). Adverse effects of diabetes and atrial fibrillation seemed to be equally important across all ages, whereas a protective effect of physical activity increased with age. Except for men with atrial fibrillation, the incidence of thromboembolic stroke increased significantly with age regardless of risk factor status, including men with normal blood pressure (P<.001). Although hemorrhagic events were less common, positive relations with cigarette smoking seemed to strengthen with age, whereas those with hypertension tended to decline. Our findings suggest that strategies for the prevention of stroke may need to account for changes in risk factor effects as they occur with age. Control of diabetes and the encouragement of active lifestyles in the elderly seem to be especially important.

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PubMed2002

Plantation work and risk of Parkinson disease in a population-based longitudinal study.

CONTEXT: Parkinson disease (PD) has an unknown cause; however, convincing evidence is emerging that indicates pesticides can selectively injure the dopaminergic system in laboratory animals. Retrospective studies in humans demonstrate a link between exposure to agricultural lifestyle factors and PD. OBJECTIVE: To determine whether working on a plantation in Hawaii and exposure to pesticides are associated with an increased risk of PD decades later. DESIGN AND SETTING: Prospective cohort study based on the island of Oahu, Hawaii, with 30 years of follow-up. Years of work on a plantation were assessed by questionnaire at study enrollment in 1965. Self-reported information on pesticide exposure was collected at a separate examination 6 years later. PARTICIPANTS: Participants were 7986 Japanese American men born between 1900 and 1919 who were enrolled in the longitudinal Honolulu Heart Program. MAIN OUTCOME MEASURES: Incident PD was determined by medical record review or by an examination conducted by a study neurologist at a later date. RESULTS: During follow-up, 116 men developed PD. Age-adjusted incidence increased significantly among men who worked more than 10 years on a plantation. The relative risk of PD was 1.0 (95% confidence interval, 0.6-1.6), 1.7 (95% confidence interval, 0.8-3.7), and 1.9 (95% confidence interval, 1.0-3.5) for men who worked on a plantation 1 to 10 years, 11 to 20 years, and more than 20 years compared with men who never did plantation work (P =.006, test for trend). Age-adjusted incidence of PD was higher in men exposed to pesticides than in men not exposed to pesticides although this was not statistically significant (P =.10, test for trend). CONCLUSION: These longitudinal observations regarding plantation work in Hawaii support case-control studies suggesting that exposure to pesticides increases the risk of PD.

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PubMed2002

The diagnosis and differential diagnosis of dementia.

The initial approach to the patient with memory complaints should consist of a focused history, mental status examination, and functional assessment. Patients with MCI should be monitored every 6 to 12 months for conversion to dementia. Delirium, depression, amnestic disorders, and aphasias should be considered in the differential diagnosis of memory impairment. Once a diagnosis of dementia is made, patients should have a brain CT or MRI scan and laboratory tests to assist with determining the cause. It is crucial that dementia be recognized and evaluated at the earliest stage so as to begin appropriate therapy and allow the patient to have a role in management decisions. In the future, therapies for MCI may prevent conversion to dementia. The need for early recognition makes the development of diagnostic tools, such as quantitative or functional neuroimaging, and genetic or clinical biologic markers essential.

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PubMed2002

Age-related changes in risk factor effects on the incidence of coronary heart disease.

PURPOSE: The purpose of this report is to examine the potential for risk factor effects on the incidence of CHD to change over a broad range of ages from middle adulthood to late-life. METHODS: Findings are based on repeated risk factor measurements at four examinations over a 26-year period in men enrolled in the Honolulu Heart Program. After each examination, six years of follow-up were available to assess risk factor effects as the cohort aged from 45 to 93 years. RESULTS: Based on 18,456 person intervals of follow-up, 677 men developed CHD (3.7%). After risk factor adjustment, a positive relation between hypertension and CHD declined significantly with age (p = 0.013), primarily due to a large increase in the risk of CHD in elderly men (75 to 93) without hypertension. Effects of total cholesterol on CHD also seemed to decline with advancing age, although changes were not statistically significant. In contrast, men with diabetes had a consistent 2-fold excess risk of CHD across all age groups, while a positive association with body mass index in younger men (45 to 54) became negative in those who were the oldest (75 to 93). Due to infrequent smoking in the elderly, associations between smoking and CHD weakened with age. In the oldest men (75 to 93), alcohol intake was unrelated to CHD, while effects of sedentary life-styles on promoting CHD appeared stronger than in those who were younger. CONCLUSION: Findings suggest that changes in risk factor effects on the incidence of CHD with advancing age may require updated strategies for CHD prevention as aging occurs.

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PubMed2002

Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants.

Clinicopathologic data from 285 autopsies were analyzed. The decedents were long-standing participants in the Honolulu-Asia Aging Study, a prospective epidemiologic investigation of stroke, neurodegenerative diseases, and aging. We assessed the prevalence at death of four primary neuropathologic processes using specific microscopic lesions as indicators. An algorithm was developed to assign each decedent to one of six subsets, corresponding to pathologic dominance by microvascular lesions (14% of decedents), Alzheimer lesions (12%), hippocampal sclerosis (5%), cortical Lewy bodies (5%), codominance by two or more primary processes (9%), or without a dominant pathologic process recognized (55%). Definite or probable dementia had been identified in 118 of the decedents. The proportions of men in each subset identified as demented were (in the same order) 57%, 53%, 79%, 57%, 76%, and 25%. In this autopsied panel of older Japanese-American men, the importance of microvascular lesions as a likely explanation for dementia was nearly equal to that of Alzheimer lesions. The cerebrovascular lesion type most essentially and inclusively related to dementia was multiple microinfarction.

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