Lon R. White

Midlife blood pressure and dementia: the Honolulu–Asia aging study☆ ☆

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

The Cognitive Abilities Screening Instrument (CASI): A Practical Test for Cross-Cultural Epidemiological Studies of Dementia

The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. Scores of the Mini-Mental State Examination, the Modified Mini-Mental State Test, and the Hasegawa Dementia Screening Scale can also be estimated from subsets of the CASI items. Pilot testing conducted in Japan and in the United States has demonstrated its cross-cultural applicability and its usefulness in screening for dementia, in monitoring disease progression, and in providing profiles of cognitive impairment. Typical administration time is 15 to 20 minutes. Record form, manual, videotape of test administration, and quizzes to qualify potential users on the administration and scoring of the CASI are available upon request.

Frequency of bowel movements and the future risk of Parkinson’s disease

Background: Constipation is frequent in PD, although its onset in relation to clinical PD has not been well described. Demonstration that constipation can precede clinical PD could provide important clues to understanding disease progression and etiology. The purpose of this report is to examine the association between the frequency of bowel movements and the future risk of PD. Methods: Information on the frequency of bowel movements was collected from 1971 to 1974 in 6790 men aged 51 to 75 years without PD in the Honolulu Heart Program. Follow-up for incident PD occurred over a 24-year period. Results: Ninety-six men developed PD an average of 12 years into follow-up. Age-adjusted incidence declined consistently from 18.9/10,000 person-years in men with <1 bowel movement/day to 3.8/10,000 person-years in those with >2/day (p = 0.005). After adjustment for age, pack-years of cigarette smoking, coffee consumption, laxative use, jogging, and the intake of fruits, vegetables, and grains, men with <1 bowel movement/day had a 2.7-fold excess risk of PD versus men with 1/day (95% CI: 1.3, 5.5; p = 0.007). The risk of PD in men with <1 bowel movement/day increased to a 4.1-fold excess when compared with men with 2/day (95% CI: 1.7, 9.6; p = 0.001) and to a 4.5-fold excess versus men with >2/day (95% CI: 1.2, 16.9; p = 0.025). Conclusions: Findings indicate that infrequent bowel movements are associated with an elevated risk of future PD. Further study is needed to determine whether constipation is part of early PD processes or is a marker of susceptibility or environmental factors that may cause PD.

Effects of walking on mortality among nonsmoking retired men

BACKGROUND The potential benefit of low-intensity activity in terms of longevity among older men has not been clearly documented. We examined the association between walking and mortality in a cohort of retired men who were nonsmokers and physically capable of participating in low-intensity activities on a daily basis. METHODS We studied 707 nonsmoking retired men, 61 to 81 years of age, who were enrolled in the Honolulu Heart Program. The distance walked (miles per day) was recorded at a base-line examination, which took place between 1980 and 1982. Data on overall mortality (from any cause) were collected over a 12-year period of follow-up. RESULTS During the follow-up period, there were 208 deaths. After adjustment for age, the mortality rate among the men who walked less than 1 mile (1.6 km) per day was nearly twice that among those who walked more than 2 miles (3.2 km) per day (40.5 percent vs. 23.8 percent, P=0.001). The cumulative incidence of death after 12 years for the most active walkers was reached in less than 7 years among the men who were least active. The distance walked remained inversely related to mortality after adjustment for overall measures of activity and other risk factors (P=0.01). CONCLUSIONS Our findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate. Encouraging elderly people to walk may benefit their health.

Early inflammation and dementia: A 25-year follow-up of the Honolulu-Asia aging study†

Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long‐term prospective association between dementia and high‐sensitivity C‐reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968–1970) and subsequently were reexamined 25 years later for dementia in the Honolulu‐Asia Aging Study (1991–1996). In a random subsample of 1,050 Honolulu‐Asia Aging Study cases and noncases, high‐sensitivity C‐reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high‐sensitivity C‐reactive protein, men in the upper three quartiles had a 3‐fold significantly increased risk for all dementias combined, Alzheimers disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.

CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study

Objective: To investigate the relationship of amyloid neuropathology to postmortem CSF Aβ 42 levels in an autopsy sample of Japanese American men from the population-based Honolulu–Asia Aging Study. Methods: In 1991, participants were assessed and diagnosed with dementia (including subtype) based on published criteria. At death CSF was obtained from the ventricles. Neuritic plaques (NP) and diffuse plaques in areas of the neocortex and hippocampus were examined using Bielschowsky silver stains. Cerebral amyloid angiopathy (CAA) was measured by immunostaining for β4 amyloid in cerebral vessels in the neocortex. Neuropathologically confirmed AD was diagnosed using Consortium to Establish a Registry for Alzheimer’s Disease criteria. In 155 autopsy samples, log transformed linear regression models were used to examine the association of NP and CAA to Aβ 42 levels, controlling for clinical dementia severity, time between diagnosis and death, age at death, brain weight, hours between death and collection of CSF, education, and APOE genotype. Results: Higher numbers of NP in the neocortex (p trend = 0.001) and in the hippocampus (p trend = 0.03) were strongly associated with lower levels of Aβ 42. Individuals with CAA had lower Aβ 42 levels (β coefficient = −0.48; 95% CI −0.9, −0.1). Compared to participants with a diagnosis of clinical dementia, those with pathologically confirmed AD had lower Aβ 42 levels (β coefficient = −0.74; 95% CI −1.4, −0.1). Conclusion: The current study suggests that lower Aβ 42 levels reflect neuropathologic processes implicated in amyloid-related pathologies, such as NP and CAA.

Association of olfactory dysfunction with risk for future Parkinson's disease

Although olfactory dysfunction is commonly associated with Parkinsons disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community‐based population. This study examines the association of olfactory dysfunction with future development of PD in Honolulu‐Asia Aging Study cohort members

Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study

We determined the prevalence of dementia and probable senile dementia of the Alzheimer type (SDAT) for biennial Exam 17 of the Framingham cohort (1982/1983). The prevalence of dementia was 30.5/1,000 for men and 48.2/1,000 for women and increased with advancing age. Cases of probable SDAT constituted 55.6% of all dementia cases. The prevalence of SDAT was 11.7/1,000 for men and 30.1/1,000 for women and also increased with advancing age. Prevalence of dementia and orobable SDAT were greater for women than men. The fema1e:male ratio of prevalence for cohort members 75 years of age and older was 1.8 for all cases of dementia and 2.8 for cases of probable SDAT.

Incidence of dementia and probable Alzheimer's disease in a general population The Framingham Study

objective: To determine the incidence of dementia and Alzheimers disease (AD) in a general population sample. Background: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. Methods: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini-Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. Results: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. Conclusions: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years.

Race and sex differences in hip fracture incidence.

Incidence rates for hip fracture in the United States were estimated using non-federal hospital discharges from the National Hospital Discharge Survey for the years 1974-1979. Age-specific incidence curves for women and for men showed similar patterns of increase in risk with age, with risks approximately doubling every five years after age 50. Age-specific rates by five-year age groups were compared among the four race-sex groups. No significant differences were observed between Black females, Black males, and White males. In contrast, rates for White females were one and one-half to four times those for Black females after age 40 and were approximately double those for White males after age 50. Analysis based on an independent data source of non-federal hospital discharges in Washington, DC confirmed these relationships. In the Washington study, White women were at twice the risk for hip fracture (controlled for age) compared with Black women and at 2.7 times the risk for hip fracture (controlled for age) compared to White men. No significant differences were observed between Black women and Black men.