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AlzRisk Paper Detail
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Reference: Abbott, 2004
Cohort: Honolulu-Asia Aging Study
Risk Factor: Physical Activity


Average Follow-up Time Detail
Examination for baseline characteristics was between 1991-1993 and follow-up for incident dementia occurred at two repeat examinations in 1994-1996 and 1997-1999.

Exposure Detail
"At the beginning of follow-up (1991-1993), study participants were asked about the average amount of distance walked per day."

Ethnicity Detail
Japanese-American men living in Hawaii.

Screening and Diagnosis Detail
Screening Method:
CASICognitive Abilities Screening Instrument (Teng 1994)

AD Diagnosis:
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)

Total dementia diagnosis: Dementia via DSM-III-R and VaD via California's Alzheimer's Disease Diagnostic and Treatment Centers.

"Cases of dementia were identified through a system of screening for cognitive function following a rigid study protocol.12 Initial screening considered a participant's age and cognitive performance on the Cognitive Abilities Screening Instrument (CASI). The latter is a comprehensive measure of intellectual function that has been developed and validated for use in cross-cultural studies.16 Performance scores range from 0 to 100, with high scores indicating better cognitive function than low scores. Scores lower than 74 were selected a priori as an indicator of possible dementia during dementia screening.12 The value of 74 corresponds closely to a score of 22 on the Mini-Mental State Examination.17

"The CASI was administered twice at the baseline examination (1991-1993) as part of 3 phases of screening.12 All men with an initial CASI score of lower than 74 were invited to return for a second phase of evaluation. At phase 2, if a repeat CASI score was also lower than 74 or if a score on the Informant Questionnaire on Cognitive Decline in the Elderly18 was 3.6 or higher, a return visit was requested for a complete dementia assessment. Among the remaining men, recruitment for subsequent phases was based on a sampling scheme that increased the likelihood for selection in older men and in men with intermediate vs high CASI scores. Through this process of screening, 145 cases of prevalent dementia were observed. As noted, these men were excluded from this study. For these men with prevalent dementia, 96% had a CASI score lower than 74. Among men without dementia, 11% had a CASI score lower than 74. As noted, 75 men with poor cognitive function (defined as an initial CASI score <74) whose dementia status could not be confirmed were excluded from follow-up.

"For the follow-up examinations used to identify incident cases of dementia reported in this study, the CASI was administered once.19 For the first follow-up examination (1994-1996), participants were recruited for complete dementia assessment if 1 of the following occurred: the repeat CASI score declined at least 9 points from the initial baseline CASI score; the repeat CASI score was 77 or lower and the participant had less than 12 years of education; or the repeat CASI score was 79 or lower and the participant had 12 or more years of education. At the second follow-up examination (1997-1999), complete assessment was requested when a CASI score was lower than 70. In all instances, trained technicians administered the CASI without regard to physical function and activity.

"For diagnosis of dementia, information from a variety of sources was considered, including a history given by a family member, a standardized neuropsychological evaluation, and a thorough neurological examination. Laboratory findings and computed tomography were also used for the classification of dementia. Final diagnoses were assigned by a consensus panel consisting of a neurologist and additional physicians with expertise in dementia in the absence of information on physical activity. Participants with dementia met criteria based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition.20 Research criteria established by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were used in the diagnosis of Alzheimer disease.21 Alzheimer disease was defined to include cases of dementia in which Alzheimer disease was judged to be the sole or primary cause. Diagnoses of vascular dementia adhered to the criteria of the California Alzheimer's Disease Diagnostic and Treatment Centers.22 Vascular dementia included cases in which a vascular cause was considered the sole or primary cause."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

***The paper reports the association using categories of miles walked per day with >2 mile/d (highest PA category) as the reference category.

"To estimate the relative hazard (RH) of dementia (and 95% confidence interval [CI]) between ranges of distance walked, proportional hazards regression models were used.29 Time to dementia was defined as the time to diagnosis of dementia cases observed in the course of follow-up. Men who died without a diagnosis of dementia prior to the end of follow-up were censored at the time of death and those who remained alive were censored at the close of the second repeat examination (1999). Adjustments were made for age, the markers of preclinical dementia, and the other characteristics as separate independent variables in a single regression model. Presence of apolipoprotein {epsilon}4 alleles (yes vs no), status as a skilled professional (yes vs no), hypertension, diabetes, and prevalent coronary heart disease were modeled as dichotomous variables and the other characteristics were modeled as continuous variables. All reported P values were based on 2-sided tests of significance and P values <.05 were considered statistically significant."

Taafe et al (2008) examined 2,263 HAAS participants for the association between physical activity and AD and total dementia stratified by level of performance-based physical function. There were 83 cases of AD (6.2 per 1000 person-years). There was a significant interaction effect on the
risk of AD between physical activity and physical function
after adjustment for age (p=0.012) and the other study
characteristics (p=0.021). When stratified by physical function score (low, moderate high), there was a significant trend in the age-adjusted model for a reduced risk of AD with increasing levels of physical activity in men with poor physical function (p=0.033), but not in men with moderate or high functioning levels. In summary, risk of dementia and AD declined significantly with increasing physical activity, yet similar associations were absent in men with moderate and high physical function.

AD Covariates:
Aage
Eeducation
APOE4APOE e4 genotype
BMIbody mass index
CHDcoronary heart disease
DMdiabetes mellitus
HTNhypertension
Oother
PPphysical performance
TCtotal cholesterol

TD Covariates:
Aage
Eeducation
APOE4APOE e4 genotype
BMIbody mass index
CHDcoronary heart disease
DMdiabetes mellitus
HTNhypertension
Oother
PPphysical performance
TCtotal cholesterol

The authors reported multivariate analysis adjusting for: age, presence of apolipoprotein e4 alleles, Cognitive Abilities Screening Instrument score, decline in physical activity since mid adulthood, physical performance score, years of education, body mass index, childhood years spent living in Japan, status as a skilled professional, hypertension, diabetes, prevalent coronary heart disease, and total cholesterol.