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AlzRisk Paper Detail

Reference: Peila, 2004
Cohort: Honolulu-Asia Aging Study
Risk Factor: Diabetes Mellitus

Average Follow-up Time Detail
Baseline assessments took place between 1991 and 1993. Two follow-up assessments were done to determine dementia status: the first between 1994-1996, and the second between 1997-1999. The authors report participation rates for the first and second follow-up assessments of 84% and 90%, respectively.

Exposure Detail
Insulin was measured following an overnight fast using a double-antibody radioimmunoassay method. The authors categorized insulin into three levels for analysis: low (<7.2 mIU/L), medium (7.2-23.0 mIU/L) and high (>23.0 mIU/L).

"In 1991, glucose and insulin levels were measured after an overnight fast. Insulin was measured by a double-antibody radioimmunoassay method...For the analysis, the study sample was divided in three groups based on the insulin levels—low (insulin <7.20 mIU/L), medium (insulin between 7.20 mIU/L and 23.0 mIU/L), and high (insulin >23.0 mIU/L)—so that the cutoffs of the groups were the 15th and the 85th percentiles of the insulin distribution, corresponding to one SD from the mean."

Ethnicity Detail
The study cohort was made up of Japanese-American men living in Hawaii as described here.

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-III-R.

All participants received the 100-point Cognitive Abilities Screening Instrument (CASI), a well recognized instrument to assess cognitive function validated among Japanese and Western sample populations. In the prevalent phase, CASI score and age were used to identify a subgroup for dementia evaluation. At the follow-up exam, participants with a CASI score less than an education-adjusted cutoff (77 for those with low education and 79 for those with high education) or an absolute drop >9 CASI points from baseline underwent a specific dementia examination. At each exam, evaluation of clinical dementia included a proxy interview, detailed neuropsychological assessment, neurological examination, and neuroimaging. Final diagnosis of clinical dementia was determined by a consensus committee that included the study neurologist and at least two other physicians expert in geriatric medicine and dementia.

"Dementia was diagnosed according to DSM-III-R criteria (19). Probable and possible AD were diagnosed following the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (20), and diagnosis of VsD was based on the California Alzheimer’s Disease Diagnostic and Treatment Centers guidelines (21). Diagnosis of dementia due to multiple etiologies included AD with cerebrovascular disease (CVD) for which probable or possible AD was either the primary or secondary cause of dementia and that was accompanied by probable or possible VaD. For these diagnoses, clinical criteria and neruoimaging data were used, as suggested by the DSM-IV criteria (22)."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

"We examined the association of fasting insulin level to dementia with a Cox-proportional-hazard regression model using age as the time scale30 and with the nonparametric log-rank test for equality of survivor functions. Age at dementia onset was assigned at the midpoint date between the last examination without dementia and the first in which the subject was diagnosed with dementia. Subjects who died or did not return to the next follow-up were censored as of the time of the last evaluation."

Individuals with vascular dementia and other types of dementia were excluded from the analysis which used Alzheimer's Disease as the outcome.

AD Covariates:
APOE4APOE e4 genotype
FGLUfasting glucose

TD Covariates:
APOE4APOE e4 genotype
FGLUfasting glucose