Coffee Intake in Midlife and Risk of Dementia and its Neuropathologic Correlates

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

Midlife milk consumption and substantia nigra neuron density at death

OBJECTIVE: To examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study. METHODS: Milk intake data were collected from 1965 to 1968 in 449 men aged 45–68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm(2)) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s. RESULTS: Neuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%–55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent. CONCLUSIONS: Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study

Cognitive Deficits 3 to 6 Years Before Dementia Onset in a Population Sample: The Honolulu-Asia Ageing 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

Prestroke Weight Loss Is Associated With Poststroke Mortality Among Men in the Honolulu-Asia Aging Study

Objective To examine baseline prestroke weight loss and poststroke mortality among men. Design Longitudinal study of late-life prestroke body mass index (BMI), weight loss, and BMI change (midlife to late life) with up to 8-year incident stroke and mortality follow-up. Setting Community-based aging study data. Participants Japanese-American men (N=3581; age range, 71–93y) who were stroke free at baseline. Interventions Not applicable. Main Outcome Measure Poststroke mortality: 30 days poststroke, analyzed with stepwise multivariable logistic regression; and long-term poststroke (up to 8y), analyzed with stepwise multivariable Cox regression. Results Weight loss (4.5kg decrements) was associated with increased 30-day poststroke mortality (adjusted odds ratio=1.48; 95% confidence interval [CI], 1.14–1.92), long-term mortality after incident stroke (all types, n=225; adjusted hazards ratio (aHR)=1.25; 95% CI, 1.09–1.44), and long-term mortality after incident thromboembolic stroke (n=153; aHR=1.19; 95% CI, 1.01 to 1.40). Men with overweight/obese late-life BMI (≥25kg/m2, compared with healthy/underweight BMI) had increased long-term mortality after incident hemorrhagic stroke (n=54; aHR=2.27; 95% CI, 1.07–4.82). Neither desirable nor excessive BMI reductions (vs no change/increased BMI) were associated with poststroke mortality. In the overall sample (N=3581), nutrition factors associated with increased long-term mortality included the following: (1) weight loss (10lb decrements; aHR=1.15; 95% CI, 1.09–1.21), (2) underweight BMI (vs healthy BMI; aHR=1.76; 95% CI, 1.40–2.20), and (3) both desirable and excessive BMI reductions (vs no change or gain, separate model from weight loss and BMI; aHR range, 1.36–1.97; P<.001). Conclusions Although obesity is a risk factor for stroke incidence, prestroke weight loss was associated with increased poststroke (all types and thromboembolic) mortality. Overweight/obese late-life BMI was associated with increased posthemorrhagic stroke mortality. Desirable and excessive BMI reductions were not associated with poststroke mortality. Weight loss, underweight late-life BMI, and any BMI reduction were all associated with increased long-term mortality in the overall sample.peerReviewe

Change in Blood Pressure and Incident Dementia A 32-Year Prospective Study

Studies of the association of high blood pressure [BP] to 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 and diastolic BP measured at six examinations and dementia assessed at the final three. In an analysis of 1890 men who completed all six exams, 112 diagnosed with incident dementia at exam 6 were compared to the 1778 survivors without dementia. Trajectories in systolic and diastolic BP up to and including the sixth examination were estimated with a repeated measures analysis using 3 splines. From mid- to late-life, men who went on to develop dementia had an additional age-adjusted increase in systolic BP of 0.26 (95% CI 0.01-0.51) mmHg per year compared to survivors without dementia. Over the late-life examinations this group had an additional age-adjusted decline in systolic BP of 1.36 (0.64-2.07) mmHg 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 to men who did not, those who did develop dementia have had a greater increase, followed by a greater decrease in systolic BP. Both these trends are modified by antihypertensive therapy

Physical activity, physical function, and incident dementia in elderly men: The Honolulu-Asia Aging Study

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. Copyright 2008 by The Gerontological Society of America

Electrocardiographic changes predate Parkinson's disease onset.

Autonomic nervous system involvement precedes the motor features of Parkinson's disease (PD). Our goal was to develop a proof-of-concept model for identifying subjects at high risk of developing PD by analysis of cardiac electrical activity. We used standard 10-s electrocardiogram (ECG) recordings of 60 subjects from the Honolulu Asia Aging Study including 10 with prevalent PD, 25 with prodromal PD, and 25 controls who never developed PD. Various methods were implemented to extract features from ECGs including simple heart rate variability (HRV) metrics, commonly used signal processing methods, and a Probabilistic Symbolic Pattern Recognition (PSPR) method. Extracted features were analyzed via stepwise logistic regression to distinguish between prodromal cases and controls. Stepwise logistic regression selected four features from PSPR as predictors of PD. The final regression model built on the entire dataset provided an area under receiver operating characteristics curve (AUC) with 95% confidence interval of 0.90 [0.80, 0.99]. The five-fold cross-validation process produced an average AUC of 0.835 [0.831, 0.839]. We conclude that cardiac electrical activity provides important information about the likelihood of future PD not captured by classical HRV metrics. Machine learning applied to ECGs may help identify subjects at high risk of having prodromal PD

Midlife milk consumption and substantia nigra neuron density at death

ObjectiveTo examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.MethodsMilk intake data were collected from 1965 to 1968 in 449 men aged 45-68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm(2)) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.ResultsNeuron density was lowest in nonsmoking decedents who consumed high amounts of milk (&gt;16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake &gt;16 oz/d vs intake that was less (95% confidence interval 22.7%-55.7%, p &lt; 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.ConclusionsMilk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study