-
Frederick P Bellinger,
Arjun V Raman,
Rachel H Rueli,
Miyoko T Bellinger,
Andrea S Dewing,
Lucia A Seale,
Marilou A Andres,
Jane H Uyehara-Lock, Lon R White,
G Webster Ross,
Marla J Berry
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress and oxidized dopamine contribute to the degeneration of the nigrostriatal pathway in Parkinson's disease (PD). Selenoproteins are a family of proteins containing the element selenium in the form of the amino acid selenocysteine, and many of these proteins have antioxidant functions. We recently reported changes in expression of the selenoprotein, phospholipid hydroperoxide glutathione peroxidase GPX4 and its co-localization with neuromelanin in PD brain. To further understand the changes in GPX4 in PD, we examine here the expression of the selenium transport protein selenoprotein P (Sepp1) in postmortem Parkinson's brain tissue. Sepp1 in midbrain was expressed in neurons of the substantia nigra (SN), and expression was concentrated within the centers of Lewy bodies, the pathological hallmark of PD. As with GPX4, Sepp1 expression was significantly reduced in SN from PD subjects compared with controls, but increased relative to cell density. In putamen, Sepp1 was found in cell bodies and in dopaminergic axons and terminals, although levels of Sepp1 were not altered in PD subjects compared to controls. Expression levels of Sepp1 and GPX4 correlated strongly in the putamen of control subjects but not in the putamen of PD subjects. These findings indicate a role for Sepp1 in the nigrostriatal pathway, and suggest that local release of Sepp1 in striatum may be important for signaling and/or synthesis of other selenoproteins such as GPX4.
Journal of Parkinson's disease. 10/2012; 2(2):115-126.
-
G Webster Ross,
John E Duda,
Robert D Abbott,
Edo Pellizzari,
Helen Petrovitch,
Diane B Miller,
James P O'Callaghan,
Caroline M Tanner,
Joseph V Noorigian,
Kamal Masaki,
Lenore Launer, Lon R White
[show abstract]
[hide abstract]
ABSTRACT: Although organochlorines have been reported more frequently in Parkinson's disease (PD) brains than in controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during midlife, represent a population well suited to determining the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS. The study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used to identify Lewy bodies and Lewy neurites. With the potential for spurious associations to appear between Lewy pathology and 17 organochlorine compounds found in at least 1 brain, initial assessments identified heptachlor epoxide isomer b, methoxychlor, and benzene hexachloride b as being most important. The prevalence of Lewy pathology was 75% (6 of 8) among brains with any 2 of the 3 compounds, 48.8% (79 of 162) among those with 1, and 32.7% (18 of 55) for those with neither (P = .007 test for trend). Although findings persisted after removing cases with PD and dementia with Lewy bodies and after adjustment for age at death, body mass index, pack-years of cigarette smoking, and coffee intake (P = .013), the results were insignificant when correcting for multiple testing. Although consistent with earlier accounts of an association between organochlorines and clinical PD, associations with Lewy pathology warrant further study. © 2012 Movement Disorder Society.
Movement Disorders 09/2012; 27(11):1418-24. · 4.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: β-Amyloid (Aβ), a vasoactive protein, and elevated blood pressure (BP) levels are associated with Alzheimer disease (AD) and possibly vascular dementia. We investigated the joint association of midlife BP and Aβ peptide levels with the risk for late-life AD and vascular dementia. Subjects were 667 Japanese-American men (including 73 with a brain autopsy), from the prospective Honolulu Heart Program/Honolulu Asia Aging Study (1965-2000). Midlife BP was measured starting in 1971 in participants with a mean age of 58 years; Aβ was measured in specimens collected in 1980-1982, and assessment of dementia and autopsy collection started in 1991-1993. The outcome measures were prevalent (present in 1991-1993) and incident AD (n=53, including 38 with no contributing cardiovascular disease) and vascular dementia (n=24). Cerebral amyloid angiopathy, β-amyloid neuritic plaques, and neurofibrillary tangles were evaluated in postmortem tissue. The risk for AD significantly increased with lower levels of plasma Aβ (Aβ1-40 hazard ratio: 2.1 [95% CI: 1.4 to 3.1]; Aβ1-42 hazard ratio: 1.6 [95% CI: 1.1 to 2.3]). Evidence of interaction between diastolic BP and plasma Aβ (1-40 P(interaction)<0.05; 1-42 P(interaction)<0.07) levels indicated that the Aβ-related risk for AD was higher when BP was higher. Low plasma Aβ was associated with the presence of cerebral amyloid angiopathy (P(trend)<0.05) but not the other neuropathologies. Aβ plasma levels start decreasing ≥15 years before AD is diagnosed, and the association of Aβ to AD is modulated by midlife diastolic BP. Elevated BP may compromise vascular integrity leading to cerebral amyloid angiopathy and impaired Aβ clearance from the brain.
Hypertension 03/2012; 59(4):780-6. · 6.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Honolulu-Asia Aging Study is a population based prospective study of neurodegenerative and cerebrovascular diseases in 8006 Japanese-American men, born 1900-1919. Beginning in 1965, environmental, life-style, and physical characteristics, including many features associated with pre-motor Parkinson's disease (PD), were ascertained at examinations over 40 years. Men with clinical PD were identified and final diagnosis was made by consensus of two neurologists. Additionally, brain autopsies have been sought since 1991 allowing use of incidental Lewy bodies and neuronal loss in the substantia nigra (SN) and locus coeruleus (LC) as additional endpoints for the PD process. Impaired olfaction, constipation, slow reaction time, excessive daytime sleepiness, and impaired executive function were all associated with future development of PD and/or with increased likelihood of either incidental Lewy bodies or neuronal loss in the SN or LC. Compared with persons without any, those with combinations of 2 or more of these pre-motor features had up to a 10-fold increase in risk for development of PD. While low specificity and positive predictive value limit the use of these clinical features alone to identify pre-motor PD, these methods may be useful for identifying a high risk group for participation in intervention trials aimed at preventing or slowing the progression of PD.
Parkinsonism & Related Disorders 01/2012; 18 Suppl 1:S199-202. · 3.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia.
Case-control study nested in a prospective cohort.
The Honolulu-Asia Aging Study, Oahu, Hawaii.
Three thousand four hundred sixty-eight Japanese-American men (mean age 52 in 1965-1968) examined for dementia 25 years later.
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.
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.
Among Japanese-American men, having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life.
Journal of the American Geriatrics Society 12/2011; 60(1):118-23. · 3.74 Impact Factor
-
Lon R White
Journal of Alzheimer's disease: JAD 11/2011; 28(2):481-3. · 3.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was untaken to investigate the association of micro brain infarcts (MBIs) with antemortem global cognitive function (CF), and whether brain weight (BW) and Alzheimer lesions (neurofibrillary tangles [NFTs] or neuritic plaques [NPs]) mediate the association.
Subjects were 436 well-characterized male decedents from the Honolulu Asia Aging Autopsy Study. Brain pathology was ascertained with standardized methods, CF was measured by the Cognitive Abilities Screening Instrument, and data were analyzed using formal mediation analyses, adjusted for age at death, time between last CF measure and death, education, and head size. Based on antemortem diagnoses, demented and nondemented subjects were examined together and separately.
In those with no dementia, MBIs were strongly associated with the last antemortem CF score; this was significantly mediated by BW, and not NFTs or NPs. In contrast, among those with an antemortem diagnosis of dementia, NFTs had the strongest associations with BW and with CF, and MBIs were modestly associated with CF.
This suggests that microinfarct pathology is a significant and independent factor contributing to brain atrophy and cognitive impairment, particularly before dementia is clinically evident. The role of vascular damage as initiator, stimulator, or additive contributor to neurodegeneration may differ depending on when in the trajectory toward dementia the lesions develop.
Annals of Neurology 11/2011; 70(5):774-80. · 11.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Latent growth curve (LGC) models estimate change over time in a cohort's serially obtained measurements. We have applied LGC techniques to a spatial distribution of Alzheimer's disease (AD) pathology using autopsy data from 435 participants in the Honolulu-Asia Aging Study. Neurofibrillary tangle (NFT) and neuritic plaques (NP) were distributed across differently ordered sets of anatomical regions. The gradient of spatial change in neuritic plaque (dNP), was significantly associated with that of neurofibrillary tangle (dNFT), but weakly and inversely (r = -0.12; p < 0.001). Both dNFT and dNP correlated significantly and inversely with Braak stage. Sixty-one percent of the variance in Braak stage was explained by dNFT independent of covariates. Only dNFT was significantly associated with longitudinal change in cognition. Only dNP was associated with apolipoprotein (APOE) e4 burden. This is the first application of LGC models to spatially-ordered data. The result is a quantification of the interindividual variation in the interregional vulnerability to Alzheimer's disease lesions.
Neurobiology of aging 07/2011; 33(8):1556-63. · 5.94 Impact Factor
-
Ann I Scher,
Yuan Xu,
Esther S C Korf,
Stephen W Hartley,
Menno P Witter,
Philip Scheltens, Lon R White,
Paul M Thompson,
Arthur W Toga,
Daniel J Valentino,
Lenore J Launer
[show abstract]
[hide abstract]
ABSTRACT: Hippocampal changes may be a useful biomarker for Alzheimer's disease if they are specific to dementia sub-type. We compare hippocampal volume and shape in population-based incident cases of Alzheimer's disease and vascular dementia (VaD).
Participants are Japanese-American men from the Honolulu Asia Aging Study. The following analysis is based on a sub-group of men with mild incident Alzheimer's disease (n=24: age=82.5 ± 4.6) or incident VaD (n=14: age=80.5 ± 4.5). To estimate hippocampal volume, one reader, blinded to dementia diagnosis, manually outlined the left and right formation of the hippocampus using published criteria. We used 3-D mapping methods developed at the Laboratory of Neuro Imaging (LONI) to compare regional variation in hippocampal width between dementia groups.
Hippocampal volume was about 5% smaller in the Alzheimer's disease group compared to the VaD group, but the difference was not significant. Hippocampal shape differed between the two case groups for the left (p<0.04) but not right (p<0.21) hippocampus. The specific region of the hippocampus that most consistently differed between the Alzheimer's disease and VaD cases was in the lateral portion of the left hippocampus. Our interpretation of this region is that it intersects the CA1 sub-region to a great extent but also includes the dentate gyrus (and hilar region) and subiculum.
As indicated by shape analysis, there are some differences in atrophy localisation between the Alzheimer's disease and VaD cases, despite the finding that volume of the hippocampi did not differ. These findings suggest hippocampal atrophy in Alzheimer's disease may be more focal than in VaD.
Journal of neurology, neurosurgery, and psychiatry 04/2011; 82(4):373-6. · 4.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Parkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related compounds may contribute to the degeneration characteristic of this disease.
To investigate a possible role of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4) in protection from oxidative stress, we investigated GPX4 expression in postmortem human brain tissue from individuals with and without Parkinson's disease. In both control and Parkinson's samples, GPX4 was found in dopaminergic nigral neurons colocalized with neuromelanin. Overall GPX4 was significantly reduced in substantia nigra in Parkinson's vs. control subjects, but was increased relative to the cell density of surviving nigral cells. In putamen, GPX4 was concentrated within dystrophic dopaminergic axons in Parkinson's subjects, although overall levels of GPX4 were not significantly different compared to control putamen.
This study demonstrates an up-regulation of GPX4 in neurons of substantia nigra and association of this protein with dystrophic axons in striatum of Parkinson's brain, indicating a possible neuroprotective role. Additionally, our findings suggest this enzyme may contribute to the production of neuromelanin.
Molecular Neurodegeneration 01/2011; 6(1):8. · 4.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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 (>277.5 mg/d) were less likely than men in the lowest quartile (≤115.5 mg) to have any of the lesion types (adjusted-OR, 0.45; 95% CI, 0.23-0.89; p, trend = 0.04). Coffee and caffeine intake in midlife were not associated with cognitive impairment, dementia, or individual neuropathologic lesions, although higher caffeine intake was associated with a lower odds of having any of the lesion types at autopsy.
Journal of Alzheimer's disease: JAD 12/2010; 23(4):607-15. · 3.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain iron promotes neurodegeneration in Parkinson's disease (PD). While hemoglobin (Hb) is the most abundant source of peripheral iron in humans, its relationship with PD is uncertain. This report examines the association between Hb in late life and PD incidence. From 1991 to 1993, Hb was measured in 3507 men in the Honolulu-Asia Aging Study. Men were aged 71-93 years and without PD. Participants were followed until 2001 for incident PD. Hb levels declined markedly with age. For men aged 71-75 years, 14.8% had levels < 14 g/dL versus 53.6% in those aged 86 and older (p < 0.001). During follow-up, 47 men developed PD (19.8/10,000 person-years). After age adjustment, PD incidence rose significantly from 10.3 to 34.9/10,000 person-years as Hb increased from < 14 to ≥ 16 g/dL (p = 0.024; relative hazard 3.2; 95% confidence interval, 1.2-8.9). Associations persisted after accounting for early mortality and adjustments for concomitant risk factors. While Hb declines with advancing age, evidence suggests that Hb that remains high in elderly men is associated with an increased risk of PD.
Neurobiology of aging 08/2010; 33(5):914-20. · 5.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the effect of walking on incident depressive symptoms in elderly Japanese-American men with and without chronic disease.
Prospective cohort study.
The Honolulu-Asia Aging Study.
Japanese-American men aged 71 to 93 at baseline.
Physical activity was assessed according to self-reported distance walked per day. Depressive symptoms were measured using an 11-question version of the Centers for Epidemiologic Studies Depression Scale (CES-D 11) at the fourth examination (n=3,196) and at the seventh examination 8 years later (1999/00, n=1,417). Presence of incident depressive symptoms was defined as a CES-D 11 score of 9 or greater or taking antidepressants at Examination 7. Subjects with prevalent depressive symptoms at baseline were excluded.
Age-adjusted 8-year incident depressive symptoms were 13.6%, 7.6%, and 8.5% for low (<0.25 miles/day), intermediate (0.25-1.5 miles/day), and high (>1.5 miles/day) walking groups at baseline (P=0.008). Multiple logistic regression analyses, adjusted for age, education, marital status, cardiovascular risk factors, prevalent diseases, and functional impairment, showed that those in the intermediate and highest walking groups had significantly lower odds of developing 8-year incident depressive symptoms (odds ratio (OR)=0.52, 95% confidence interval (CI)=0.32-0.83, P=.006 and OR=0.61, 95% CI= 0.39-0.97, P=.04, respectively). Analysis found that this association was significant only in participants without chronic diseases (coronary heart disease, cerebrovascular accident, cancer, Parkinson's disease, dementia, or cognitive impairment) at baseline.
Daily physical activity (≥0.25 mile/day) is significantly associated with lower risk of 8-year incident depressive symptoms in elderly Japanese-American men without chronic disease at baseline.
Journal of the American Geriatrics Society 08/2010; 58(8):1447-52. · 3.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To estimate the potential benefits of lowering systolic blood pressure (SBP) toward preventing late-life dementia, we estimated the population-attributable risk of elevated SBP for dementia. Analyses are based on the cohort of 8006 Japanese American men (born 1900-1919) followed since 1965 as a part of the Honolulu Heart Program, continued as the Honolulu Asia Aging Study. Midlife cardiovascular risk factors and late-life brain function are well described. We estimated the population-attributable risk of dementia cases attributed to midlife SBP, grouped by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria (<120, 120 to <140, and > or =140 mm Hg), taking into account treatment history, confounding factors, and competitive risk for death. The analysis is based on 7878 subjects, including 491 cases of dementia, with a mean interval of 25 years between measurement of blood pressure and dementia diagnosis. Compared with those with SBP <120 mm Hg, untreated, and <50 years of age at baseline, 17.7% (95% CI: 4.6% to 29.1%) of the cases were attributable to prehypertensive levels (SBP: 120 to <140 mm Hg) of SBP, translating into 11 excess cases per 1000. Among those who did not report taking antihypertensive medication in midlife, 27% (95% CI: 8.9% to 42.1%) of dementia cases can be attributed to systolic BP > or =120 mm Hg, translating into 17 excess cases per 1000. Although population-attributable risk estimates for population subgroups may differ by relative risk for dementia or prevalence of elevated levels of blood pressure, these data suggest that reducing midlife systolic BP is an effective prevention strategy to reduce risk for late-life dementia.
Hypertension 06/2010; 55(6):1352-9. · 6.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Studies of the association of high blood pressure (BP) with dementia are not consistent. Understanding long-term trajectories in blood pressure of those who do and do not develop dementia can help clarify the issue. The Honolulu Heart Program/Honolulu-Asia Aging Study followed a cohort of Japanese American men for an average of 32 years, with systolic BP (SBP) and diastolic BP (DBP) measured at 6 examinations and dementia assessed at the final 3. In an analysis of 1890 men who completed all 6 of the exams, 112 diagnosed with incident dementia at examination 6 were compared with the 1778 survivors without dementia. Trajectories in SBP and DBP up to and including the sixth examination were estimated with a repeated-measures analysis using 3 splines. From midlife to late life, men who went on to develop dementia had an additional age-adjusted increase in SBP of 0.26 mm Hg (95% CI: 0.01 to 0.51 mm Hg) per year compared with survivors without dementia. Over the late-life examinations, this group had an additional age-adjusted decline in SBP of 1.36 mm Hg (95% CI: 0.64 to 2.07 mm Hg) per year. These associations were strongest for vascular dementia and were reduced substantially in men who were previously taking antihypertensive medication. Similar changes in diastolic BP were observed, but only for vascular dementia, and the findings were not modified by antihypertensive treatment. Over a 32-year period, compared with men who did not, those who did develop dementia had a greater increase, followed by a greater decrease, in SBP. Both of these trends are modified by antihypertensive therapy.
Hypertension 07/2009; 54(2):233-40. · 6.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Selenium is known for its antioxidant properties, making selenoproteins candidate molecules for mitigation of neurological disorders in which oxidative stress has been implicated. The selenium transport protein, selenoprotein P, is essential for neuronal survival and function. We sought to determine whether selenoprotein P expression is associated with Alzheimer's disease pathology. We examined postmortem tissue from individuals with the hallmark lesions of Alzheimer's disease and individuals without these lesions. Selenoprotein P immunoreactivity was co-localized with amyloid-beta plaques and neurofibrillary tangles. Dense-core and other non-diffuse amyloid-beta plaques were nearly always associated with selenoprotein P immunopositive cells. Analysis of spatial distribution showed a significant association between amyloid-beta plaques and selenoprotein P. Numerous cells also exhibited immunoreactivity to selenoprotein P and intraneuronal neurofibrillary tangles. Confocal microscopy confirmed co-localization of amyloid-beta protein and selenoprotein P. These findings suggest an association of selenoprotein P with Alzheimer's pathology.
Journal of Alzheimer's disease: JAD 12/2008; 15(3):465-72. · 3.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Constipation is associated with future risk of Parkinson's disease (PD) and with incidental Lewy bodies (LB) in the locus ceruleus or substantia nigra (SN). Our purpose is to examine the independent association between bowel movement frequency in late-life and postmortem SN neuron density. Bowel movement frequency was assessed in the Honolulu-Asia Aging Study from 1991 to 1993 in 414 men aged 71 to 93 years with later postmortem evaluations. Brains were examined for LB in the SN and locus ceruleus and neurons were counted in four quadrants from a transverse section of SN. In nonsmokers, neuron densities (counts/mm(2)) for men with >1, 1, and <1 bowel movement daily were 18.5, 18.8, 10.1 (P < 0.001) for dorsomedial; 15.3, 16.4, 10.2 (P < 0.03) for ventromedial; and 18.6, 18.3, 10.9 (P = 0.011) for ventrolateral quadrants. Relationships were not significant in the dorsolateral quadrant or in any quadrant among smokers. After adjustment for age, time to death, coffee drinking, tricep skinfold thickness, excessive daytime sleepiness, cognitive function, PD, and incidental LB, density ratios in nonsmokers with 1 or more bowel movement(s) daily were significantly higher compared to those with <1 daily. Constipation is associated with low SN neuron density independent of the presence of LB.
Movement Disorders 12/2008; 24(3):371-6. · 4.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The apolipoprotein E epsilon4 (APOE epsilon4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined.
To examine the independent and combined effects of depression and APOE epsilon4 on the risk of dementia and its subtypes.
The Honolulu-Asia Aging Study, a population-based prospective cohort study of Japanese American men.
Depressive symptoms and presence of the APOE epsilon4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow-up based on neurologic assessment at 2 repeated examinations (April 1994-April 1996 and October 1997-February 1999).
Overall dementia, Alzheimer disease, and vascular dementia.
The interaction of depression and APOE epsilon4 was statistically significant in the analytical models. Compared with men with neither APOE epsilon4 nor depression, the risk of dementia in nondepressed men with APOE epsilon4 was not significant (hazard ratio, 1.1; 95% confidence interval [CI], 0.6-1.8); however, depressed men without APOE epsilon4 had a 1.6-fold greater risk (95% CI, 0.8-3.0), whereas depressed men with APOE epsilon4 had a 7.1-fold greater risk (95% CI, 3.0-16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease.
The APOE epsilon4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE epsilon4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE epsilon4 allele. Because this cohort includes only men, further investigation in women is required.
Archives of general psychiatry 09/2008; 65(8):906-12. · 12.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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).
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.
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.
In elderly men with poor physical function, increasing general physical activity may potentially confer a protective effect or delay the onset for dementia.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 06/2008; 63(5):529-35. · 4.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Understanding the variability of the hippocampus in human brain research is essential. The effect of age on the hippocampus has been explored in several studies that have been focused on either normal aging or neural degeneration. Shape analysis of magnetic resonance imaging (MRI) provides morphological measures for brain structures. This study further investigates the age effects on hippocampal morphology in three groups (104 normal controls, 24 Alzheimer's disease (AD) and 14 vascular dementia (VaD) patients). By utilizing a parametric shape analysis of hippocampal MRI scans, each individual distance map is generated and analyzed statistically. Specifically, after eliminating similarity parameters (rotation, translation, and scaling) effects for each hippocampus, an individual distance map is generated from parametric hippocampal surfaces and medial axes. Then statistical methods, including regression, and permutation tests, are applied to detect the differences in hippocampal distance maps and volumes under the effect of age in each group. Statistical analyses reveal that the loss of hippocampal volume and changes in shape are more significantly related to aging in the control group than in AD/VaD. The results also show that the asymmetry of hippocampus in healthy subjects is greater than that in either of the disease groups. Our study shows that 3D statistical shape analysis could enhance the understanding of age effects on local areas of hippocampi. However, the sample sizes of disease groups are relatively low; further studies with more AD/VaD data are needed.
NeuroImage 05/2008; 40(3):1003-15. · 5.89 Impact Factor
