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AlzRisk Paper Detail
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Reference: Schmidt, 2002
Cohort: Honolulu-Asia Aging Study
Risk Factor: Inflammatory Biomarkers


Exposure Detail
A high-sensitivity CRP (hs-CRP) assay was used. Quartiles of hs-CRP were created based on the distribution of the hs-CRP concentration in the entire study cohort.

“Nonfasting blood samples were taken from all study participants at the Honolulu Heart Program examination 2 and stored at -70°C. Hs-CRP was assayed with an enzymelinked immunosorbent assay developed by Macy and colleagues [32] in the Laboratory for Clinical Biochemistry Research, University of Vermont (Dr R. Tracy). The World Health Organization CRP reference standard was used. The interassay coefficient of variation for this assay was 5.14%. The technicians were blinded to the case-control status of the samples.”

Ethnicity Detail
Japanese-American men living in Hawaii

Screening and Diagnosis Detail
Screening Method:
CASICognitive Abilities Screening Instrument (Teng 1994)
IQ-CODEInformant Questionnaire for Cognitive Decline in the Elderly (Jorm 1989)

AD Diagnosis:
Brain Imaging
CERAD Consortium to Establish a Registry for Alzheimer’s Disease (Morris 1989)
DSM IIIR Diagnostic and Statistical Manual III-Revised
Neuropsychological examination

Total dementia definition: AD or vascular dementia (VaD), where VaD was diagnosed via California Alzheimer's Disease Diagnostic and Treatment Centers criteria (Chui et al. 1992).

Screening:“At examinations 4 and 5, all subjects underwent cognitive screening using the Cognitive Abilities Screening Instrument (CASI). The CASI is a well-recognized instrument to assess cognitive function and has been validated among Japanese and Western samples. In examination 4, the CASI score, age, and the Informant Questionnaire on Cognitive Decline in the Elderly were used to identify a subgroup for dementia evaluation. At the follow-up examination 5, all subjects with a score below the education-adjusted cutoff values or subjects who had an absolute decrease of 9 or more CASI points underwent the dementia evaluation.”

Diagnosis:“Diagnosis was based on neuropsychological testing using the Consortium to Establish a Registry for Alzheimer’s Disease battery, a neurological examination by a physician trained in dementia diagnosis, an informant interview,and neuroimaging (in 86% of the cases). All recognized subtypes of dementia were considered in the diagnostic consensus conference that included a neurologist, and at least 2 other study investigators. Dementia was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders IIIR criteria, AD according to National Institute of Neurological Disorders and Stroke–Alzheimer’s Disease and Related Dementias Association criteria,29 and VaD according to California Alzheimer’s Disease Diagnostic and Treatment Centers criteria.”

Covariates & Analysis Detail
Analysis Type:
Logistic regression

AD Covariates:
Aage
Eeducation
ABIankle-brachial index
APOE4APOE e4 genotype
AFatrial fibrillation
BMIbody mass index
CHDcoronary heart disease
DMdiabetes mellitus
DBPdiastolic blood pressure
FUTfollow up time
LVHleft ventricular hypertrophy
SMsmoking status
SHstroke history
SBPsystolic blood pressure
TCtotal cholesterol

TD Covariates:
Aage
Eeducation
ABIankle-brachial index
APOE4APOE e4 genotype
AFatrial fibrillation
BMIbody mass index
CHDcoronary heart disease
DMdiabetes mellitus
DBPdiastolic blood pressure
FUTfollow up time
LVHleft ventricular hypertrophy
SMsmoking status
SHstroke history
SBPsystolic blood pressure
TCtotal cholesterol

The authors report results from two different adjusted models. The first model is adjusted for possible confounders including level of education (categorized by low (< 8 years), middle (8-11 years), and high (>11 years)), midlife smoking status, midlife average cholesterol, midlife blood pressure, age at examination 2, years of follow-up, any apolipoprotein E ε4,and body mass index at examination 2. The second model includes all confounder variables of model 1 and the possible mediating variables: stroke, coronary heart disease, left ventricular hypertrophy, atrial fibrillation, diabetes mellitus, and the index of ankle to brachial blood pressure at the time of dementia assessment. The results entered here are from model 2. The results were the same for both models, suggesting that the association between hs-CRP and increased risk of AD is independent of cardiovascular risk factors and disease.