Get Newsletter
AlzRisk Paper Detail
Back

Reference: Larson, 2006
Cohort: Adult Changes in Thought-Group Health Cooperative
Risk Factor: Physical Activity


Average Follow-up Time Detail
These figures pertain to the analysis of total dementia, but are expected to be reasonably similar for the analysis of AD. Study participants were followed from May 1994 to October 2003.

Exposure Detail
"Physical exercise was assessed at baseline by asking participants the number of days per week they did each of the following activities for at least 15 minutes at a time during the past year: walking, hiking, bicycling, aerobics or calisthenics, swimming, water aerobics, weight training or stretching, or other exercise. The frequency of exercise was calculated by the times per week that participants engaged in any of these forms of exercise. In this study, persons who exercised at least 3 times a week, above the lowest quartile, were classified as exercising regularly."

Exercising < 3 times/ week (the reference category) represents the lowest quartile of reported physical activity.

Ethnicity Detail
"Other" ethnicities were not specified.

"Declining to participate was more common among the oldest age group (>85 years), women, and African-American and minority groups (22)."

Age Detail
"Declining to participate was more common among the oldest age group (>85 years), women, and African-American and minority groups (22)."

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 Definition: Dementia via DSM IV.

"We conducted biennial examinations to identify cases of incident dementia, when participants were rescreened with the CASI. Those who scored 86 or higher on the CASI remained in the ACT cohort. Scores on the CASI that were less than 86 at follow-up prompted a full standardized clinical examination. The results of rescreening by the CASI and by the clinical and neuropsychological examinations were reviewed at a consensus diagnosis conference that included at least the examining physician, a neuropsychologist, another study physician, and the study nurse. Persons who did not meet the criteria for dementia were considered as not having dementia and were followed in the ACT cohort (22, 23). Persons who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria (25) for dementia were considered to have incident dementia. Dementia type was determined by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria (27) for Alzheimer disease and by the DSM-IV criteria (25) for other types of dementia."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

The authors found a significant interaction of exercise and performance-based physical function for AD (p=0.021).

"To evaluate the temporal relationship of exercise with incident dementia, we used Cox proportional hazards regression models (31). Because dementia is highly age-related, we used years of age during the study as the time axis, with left truncation at age of entering the study, and kept age at baseline as a covariate in Cox models. Thereby, age was completely adjusted for in our analyses. The primary outcome was age of onset of dementia. The risk factor of primary interest was exercise at baseline. Persons who left the study before developing dementia were censored at their last examinations. Persons who remained dementia-free during the study were censored at the most recent follow-up date. The Schoenfeld residual test (32) was used to check the proportional hazards assumption. The age- and sex-adjusted hazard ratio of dementia by exercise was estimated from the Cox model.

"To investigate which baseline factors influence the association of exercise with incident dementia, we fit a separate Cox model on potentially confounding baseline variables by keeping exercise as the primary predictor and adjusting for age and sex. We examined whether the hazard ratio of dementia for exercise was changed by adding the baseline variable into a model. To further examine potential effect modifications, the interaction terms of exercise and each baseline variable were added into those Cox models. Effect modification was considered to be present if the coefficient for the interaction was found to be statistically significant (P < 0.05). Finally, we examined the hazard ratio of dementia for exercise by adjusting for all potential confounders simultaneously. For the principal analyses reported here, we compared participants in the lowest quartile of frequency of exercise (< 3 times/week) with those in the top 3 quartiles."

AD Covariates:
Aage
Eeducation
Ggender
ALCalcohol intake
APOE4APOE e4 genotype
CVDcardiovascular disease
CFcognitive function
CHDcoronary heart disease
DEPdepression
DMdiabetes mellitus
DSUdietary supplement use
HShealth status
HTNhypertension
PPphysical performance
SMsmoking status
§ Covariates for total dementia are different.

TD Covariates:
Aage
Ggender
APOE4APOE e4 genotype
CVDcardiovascular disease
CFcognitive function
CHDcoronary heart disease
DEPdepression
DMdiabetes mellitus
HShealth status
HTNhypertension
PPphysical performance

"The point estimate and confidence interval of the hazard ratio of dementia for exercise changed negligibly each time we added a single covariate to the model. Covariates that were considered included alcohol consumption, smoking, supplement use, education, presence of apolipoprotein E {epsilon}4 alleles, diabetes, hypertension, cerebrovascular disease, coronary heart disease, self-rated health, physical performance, depression, and cognitive functioning. We found that alcohol consumption, smoking, supplement use, and level of education were not associated with dementia and that adjusting for those variables did not change the point estimate for exercise; therefore, they were not included as potential confounders in the final model."