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Objective: To determine how sleep-disordered breathing, nocturnal hypoxia, and changes in sleep architecture in the elderly may be related to the development of the neuropathologic correlates of dementia., Methods: The Honolulu-Asia Aging Study is a prospective cohort study of Japanese American men in Honolulu, HI. We examined brain lesions at autopsy (Braak stage, neurofibrillary tangle and neuritic plaque counts, microinfarcts, generalized brain atrophy, lacunar infarcts, Lewy bodies [LBs], neuronal loss and gliosis in the locus ceruleus) in 167 participants who underwent polysomnography in 1999-2000 (mean age, 84 years) and died through 2010 (mean 6.4 years to death). Polysomnography measures included the apnea-hypopnea index, duration of apnea or hypopnea, duration of hypoxemia, minimum oxygen saturation (SpO₂), duration of slow-wave sleep (SWS, non-REM stage N3), and arousals., Results: Sleep duration with SpO₂ <95% was associated with higher levels of microinfarcts (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI] 1.10-13.76, comparing the highest to lowest quartiles of %sleep with SpO₂ <95%). Greater SWS duration was associated with less generalized atrophy (adjusted OR 0.32, 95% CI 0.10-1.03, comparing highest to lowest quartiles of %sleep in SWS). LBs were less common with greater %sleep with SpO₂ <95% (adjusted OR 0.17, 95% CI 0.04-0.78, comparing highest to lowest quartiles). Higher minimum SpO₂ during REM sleep was associated with less gliosis and neuronal loss in the locus ceruleus. Cognitive scores declined less among men with greater SWS duration., Conclusions: The findings support a role for lower nocturnal oxygenation and SWS in the development of microinfarcts and brain atrophy, but not Alzheimer lesions or LBs., (© 2014 American Academy of Neurology.)

Objectives: To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia., Design: Case-control study nested in a prospective cohort., Setting: The Honolulu-Asia Aging Study, Oahu, Hawaii., Participants: Three thousand four hundred sixty-eight Japanese-American men (mean age 52 in 1965-1968) examined for dementia 25 years later., Measurements: Men at low risk were defined as those with the following midlife characteristics: nonsmoking, body mass index (BMI) less than 25.0 kg/m(2) , physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruits, vegetables, cereals, and ratio of monounsaturated to saturated fat). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for developing overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD), adjusting for potential confounders., Results: Dementia was diagnosed in 6.4% of men (52.5% with AD, 35.0% with VaD). Examining the risk factors individually, BMI was most strongly associated with greater risk of overall dementia (OR = 1.87, 95% CI = 1.26-2.77; BMI > 25.0 vs <22.6 kg/m(2) ). All of the individual risk factors except diet score were significantly associated with VaD, whereas none were significantly associated with AD alone. Men with all four low-risk characteristics (7.2% of the cohort) had the lowest OR for overall dementia (OR = 0.36, 95% CI = 0.15-0.84). There were no significant associations between the combined low-risk characteristics and the risk of AD alone., Conclusion: Among Japanese-American men, having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

While animal data suggest a protective effect of caffeine on cognition, studies in humans remain inconsistent. We examined associations of coffee and caffeine intake in midlife with risk of dementia, its neuropathologic correlates, and cognitive impairment among 3494 men in the Honolulu-Asia Aging Study (mean age 52 at cohort entry, 1965-1968) examined for dementia in 1991-1993, including 418 decedents (1992-2004) who underwent brain autopsy. Caffeine intake was determined according to self-reported coffee, tea, and cola consumption at baseline. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for overall dementia, Alzheimer's disease (AD), vascular dementia (VaD), cognitive impairment (Cognitive Abilities Screening Instrument score <74), and neuropathologic lesions at death (Alzheimer lesions, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, generalized atrophy), according to coffee and caffeine intake. Dementia was diagnosed in 226 men (including 118 AD, 80 VaD), and cognitive impairment in 347. There were no significant associations between coffee or caffeine intake and risk of cognitive impairment, overall dementia, AD, VaD, or moderate/high levels of the individual neuropathologic lesion types. However, men in the highest quartile of caffeine intake (>/=411.0 mg/d) [corrected] were less likely than men in the lowest quartile (

Background: Although evidence is accumulating for a protective effect of late life physical activity on the risk of dementia, the findings are inconsistent, especially in men. We examined the association of late life physical activity and the modifying effect of physical function with future risk of dementia in a well-characterized cohort of elderly men participating in the Honolulu-Asia Aging Study (HAAS)., Methods: Physical activity by self-report and performance-based physical function was assessed in 2263 men aged 71-92 years without dementia at the baseline examination of the HAAS in 1991-1993. Follow-up for incident dementia occurred at repeat examinations conducted in 1994-1996 and 1997-1999. Analyses were based on Cox proportional hazards models with adjustment for potential confounders, including age, baseline cognitive function, education, and apolipoprotein E genotype., Results: There were 173 incident cases of dementia with a mean follow-up of 6.1 years. Although the incidence of dementia tended to decline with increasing physical activity and function, there was a significant interaction between the latter two factors on dementia risk (p =.022). For men with low physical function, high levels of physical activity were associated with half the risk of dementia versus men who were the least active (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.28-0.89), with a moderate level of physical activity also providing a protective effect (HR, 0.57; 95% CI, 0.32-0.99). Risk of dementia and Alzheimer's disease declined significantly with increasing physical activity. Findings persisted after age and risk factor adjustment. Similar associations were absent in men with moderate and high physical function., Conclusions: In elderly men with poor physical function, increasing general physical activity may potentially confer a protective effect or delay the onset for dementia.

Background: Measurement of the ankle-to-brachial index (ABI) is a noninvasive test to assess peripheral arterial disease. A low ABI is a strong correlate of cardiovascular disease and subsequent mortality. Evidence indicates the existence of vascular components in the pathogenesis of dementia. Here, we examine the association of ABI with dementia and subtypes., Methods and Results: Data are from the Honolulu-Asia Aging Study (HAAS), a prospective community-based study of 3734 Japanese American men 71 to 93 years of age at baseline in 1991 to 1993. The analysis included 2588 men who were free of dementia at the first assessment, had an ABI measure, and were examined up to 2 more times for dementia between 1994 and 1999. The sample included 240 incident cases of dementia (144 of Alzheimer's disease, 46 of vascular dementia, and 50 of dementia of other causes). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from Cox proportional-hazards models with age as the time scale after adjustment for education, year of birth, high blood pressure, body mass index, diabetes mellitus, cholesterol concentration, smoking status, alcohol consumption, and apolipoprotein E epsilon4 allele. A low ABI was associated with an increased risk of dementia and vascular dementia (HR, 1.66; 95% CI, 1.16 to 2.37; and HR, 2.25; 95% CI, 1.07 to 4.73, respectively). ABI was weakly associated with Alzheimer's disease (HR, 1.57; 95% CI, 0.98 to 2.53), particularly in the apolipoprotein E epsilon4 carriers (HR, 1.43; 95% CI, 1.02 to 1.96)., Conclusions: These results suggest that ABI, a measure of atherosclerosis, is associated with the incidence of total dementia, vascular dementia, and Alzheimer's disease in carriers of the apolipoprotein E epsilon4 allele.

We report a case series of 11 patients with excessive sweepstakes participation on initial geriatric consultation in Honolulu. Ten of these patients had dementia, mostly Alzheimer's disease, with Folstein MiniMental Status Exam scores ranging from 17-29/30. Money lost ranged from 6,600 dollars to 200,000-400,000 dollars. Physicians need to have a high index of suspicion and the public needs to be educated about simple preventive strategies.

Ethnic diversity among older patients in Hawai'i is common; yet few data exist concerning the applicability of cognitive testing instruments in non-Caucasian populations. This project aimed to determine the specificity and sensitivity of the IQCODE for the detection of cognitive impairment in a Japanese-American population. Results confirm that the IQCODE is a valuable tool for primary care physicians to detect impairment in this population.

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.

Norms for cognitive measures used to assess dementia are scant for minority groups, in particular for older Japanese Americans. Using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we compared the baseline performance of demented and nondemented Japanese Americans. Participants came from two harmonized epidemiological studies of dementia which were examined separately: the Kame Project, Seattle (350 men and women; 201 nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418 men; 120 nondemented), age 71 and older. The measures examined were Verbal Fluency; abbreviated Boston Naming; constructional praxis; and Word List Learning, Recall, and Recognition. Within each study, the CERAD measures distinguished between nondemented participants and those with mild cognitive impairment. Among persons with dementia, average level of performance decreased as severity of dementia increased. Determinants of score (age, education, language of administration, stage of dementia) varied between the two studies. Among Japanese Americans, the CERAD Neuropsychology Battery distinguished nondemented persons from those with dementia, but was less consistent in distinguishing levels of severity of dementia. This battery is useful for comparative epidemiological studies of dementia in minority populations.

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.

Antioxidants have been hypothesized to protect against Alzheimer's disease, but studies conducted in late life have been inconsistent. Risk factors measured in midlife may better predict dementia in late life because they are less affected by the disease process. The authors examined the association of midlife dietary intake of antioxidants to late-life dementia and its subtypes. Data were obtained from the Honolulu-Asia Aging Study, a prospective community-based study of Japanese-American men who were aged 45-68 years in 1965-1968, when a 24-hour dietary recall was administered. The analysis included 2,459 men with complete dietary data who were dementia-free at the first assessment in 1991-1993 and were examined up to two times for dementia between 1991 and 1999. The sample included 235 incident cases of dementia (102 cases of Alzheimer's disease, 38 cases of Alzheimer's disease with contributing cerebrovascular disease, and 44 cases of vascular dementia). Relative risks by quartile of intake were calculated using Cox proportional hazards models with age as the time scale, after adjustment for sociodemographic and lifestyle factors, cardiovascular risk factors, other dietary constituents, and apolipoprotein E e4. Intakes of beta-carotene, flavonoids, and vitamins E and C were not associated with the risk of dementia or its subtypes. This analysis suggests that midlife dietary intake of antioxidants does not modify the risk of late-life dementia or its most prevalent subtypes.

This study assessed the clinical utility of repeating the phrase "No ifs, ands, or buts" for cognitive testing in Hawaii. 242 subjects were screened; 25 (10%) had cognitive impairment. 68% of all subjects were unable to say the phrase "No ifs, ands, or buts" (83% of cognitively impaired and 67% of cognitively intact, p = 0.122). Specificity for cognitive impairment was poor.

Background: Recognition and medical record documentation of dementia in the primary care setting are thought to be poor. To our knowledge, previous studies have not examined these issues in private practice office settings within the United States., Objective: To determine the rate of unrecognized and undocumented dementia in a primary care internal medicine private practice., Methods: This was a cross-sectional study of 297 ambulatory persons aged 65 years and older attending an internal medicine private group practice within an Asian American community of Honolulu, Hawaii. Of the subjects, 95% had been with their current primary care physician for at least 1 year. Each subject's primary care physician noted the presence or absence of dementia by questionnaire at the time of an office visit. An investigating physician (V.G.V.) subsequently assessed cognitive function using the Cognitive Abilities Screening Instrument, and confirmed the presence of dementia and its severity, if present, using Benson and Cummings' criteria and the Clinical Dementia Rating Scale, respectively. A trained research assistant completed telephone interviews to proxy informants for collateral information concerning cognition, behavior, and occupational or social function. Subjects' outpatient medical records were reviewed for documentation of problems with cognition., Results: Twenty-six cases of dementia were identified. Of these 26, 17 (65%) (95% confidence interval, 44.3-82.8) were not documented in outpatient medical records; of 18 patients, 12 (67%) (95% confidence interval, 40.9-86.7) were not thought to have dementia by their physicians at the time of the office visit. Recognition and documentation rates increased with advancing stage of disease., Conclusion: Dementia is often unrecognized and undocumented in private practice settings. Arch Intern Med. 2000;160:2964-2968

Objective: To determine the prevalence and cessation of driving among older men with incident dementia in the Honolulu-Asia Aging Study., Design: Retrospective cohort data from a community-based study of incident dementia., Setting: The Honolulu Heart Program and the Honolulu-Asia Aging Study., Participants: A total of 643 men who were evaluated for the incidence of Alzheimer's disease or other dementia between the fourth and the fifth examination of the Honolulu Heart Program., Measurements: Driving history, diagnosis of dementia, grip strength, walking speed, standing balance test, interviewer's rating of vision status, and the neurologist's notes on mentions of driving behavior from informal interviews with a caregiver or family informant., Results: The prevalence of driving declined dramatically with level of cognitive functioning. Among 162 men evaluated and found to have normal cognitive functioning, 78% still drove, compared with 62% of 287 men with poor cognitive functioning but no clinical dementia, 46% of 96 men with a new diagnosis of very mild dementia (Clinical Dementia Rating = 0.5), and 22% of 98 men with a new diagnosis of mild dementia (CDR = 1). Only one of 23 men diagnosed with moderate or more severe staged incident dementia (CDR > 1) was driving. About 10% of the 59 demented persons still driving relied on co-pilots, and only one driver was reported as involved in a crash according to a review of the neurologists' notes., Conclusions: Incident dementia is a major cause of driving cessation. Based on these data, we estimate that approximately 4% of male drivers aged 75 years and older nationwide (about 175,000 men) have dementia. This number will increase with the projected growth of drivers aged 75 years and older.

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.

Objective: Growing evidence suggests that structural and functional brain reserves, thought to develop in childhood and adolescence, may be crucial in determining when cognitive impairment begins. The purpose of this report is to examine the relationship of height, as a marker of childhood development, to late-life cognitive function in a sample of elderly Japanese-American men., Method: Cognitive performance was assessed from 1991 to 1993 in the Honolulu-Asia Aging Study in 3733 men aged 71 to 93 years and related to height that was measured 25 years earlier., Results: Among the study sample, shorter men were older, leaner, and less educated than taller men. Shorter men also spent more years of their childhood living in Japan and were more likely to have had fathers in unskilled professions. After adjustment for age, the prevalence of poor cognitive performance declined consistently with increasing height from 25% in men shorter than 154 cm (61 in) to 9% in those taller than 174 cm (69 in). Excluding men with stroke or dementia did not alter the association between height and cognitive performance. Apolipoprotein E4 was unrelated to height and did not effect the association between height and cognitive function. The prevalence of Alzheimer's disease was higher in men who were 154 cm (61 in) or shorter as compared with men who were taller (4.7% vs 2.9%, respectively). There was no association between height and vascular dementia., Conclusion: Efforts to improve prenatal and early life conditions to maximize growth in childhood and adolescence could diminish or delay the expression of cognitive impairments that occur later in life. Prevention of some late-life cognitive impairments may have pediatric origins.

Objective: To determine the frequency of unrecognized dementia in a group of men found to have dementia by population survey, and to identify factors associated with the failure of a family informant to recognize significant memory impairment., Design and Setting: The Honolulu-Asia Aging Study, a population-based study of dementia among elderly Japanese-American men living on the island of Oahu, Hawaii. Data for this study were from the dementia prevalence survey, 1991-1993., Study Participants: A total of 191 noninstitutionalized men with dementia who had a reliable family informant., Main Outcome Measures: Failure of family informants to recognize a problem with thinking or memory in subjects with dementia., Results: A total of 21% of family informants failed to recognize a problem with memory among subjects subsequently found to have dementia. Among subjects with very mild dementia, 52% of family informants failed to recognize a significant memory problem compared with 13% among more severely demented subjects. Of the subjects with dementia whose family informants did recognize a memory problem, 53% failed to receive a medical evaluation for this problem. For all family informants, increasing age, fewer years of education, less severe dementia, fewer behavioral complications, fewer functional disabilities, and better performance on certain tests of memory and language were significantly associated with the family informant's failure to recognize a problem with memory. When the family informants were wives living with husbands, less severe dementia, fewer behavioral complications, fewer functional disabilities, and intact remote memory were associated with unrecognized dementia., Conclusions: Unrecognized dementia was common in our population, especially among mild cases. Cognitive screening programs for the elderly and public education policies designed to increase awareness of early signs of dementia are needed if interventions for individuals with potentially treatable dementias are to be implemented.

Objective: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere., Design and Setting: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria., Participants: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions., Main Outcome Measures: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated., Results: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia., Conclusions: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.

AimMarinesco 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.MethodsData 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.ResultsMarinesco 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.ConclusionsWhile 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.