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AlzRisk Paper Detail
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Reference: Schrijvers, 2010
Cohort: Rotterdam Study
Risk Factor: Diabetes Mellitus


Average Follow-up Time Detail
The authors reported associations between insulin resistance and risk of AD separately for three strata of follow-up time, corresponding to:

-"short follow-up" (maximum of 3 years of follow-up from baseline),
-"medium follow-up" (3 to 5.5 years of follow-up from baseline), and
-"long follow-up" (5.5 to 9.7 years of follow-up from baseline)

This row of the table presents results obtained for individuals at risk of incident AD over the "medium follow-up" time frame.

Exposure Detail
Insulin resistance was estimated using the Homeostatic Model Assessment (HOMA) technique. The value for insulin resistance is determined from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) values and is given by the formula: HOMA-IR = (FPG in mmol/l x FPI in mU/l)/22.5.

At baseline, the median HOMA-IR was 2.26, and the interquartile range was 1.56 to 3.36.

Persons with a history of diabetes at baseline were excluded. History of diabetes was determined from self-reported use of diabetes medications/treatments, or from general practitioner or past Rotterdam cohort records indicative of a diabetes diagnosis.

"Fasting blood serum was drawn during the examination at the research center. The blood was stored at -80°C in a number of 5-mL aliquots. Glucose levels were measured within 1 week of sampling using the glucose hexokinase method.9 The remaining serum was kept frozen for later analyses. In 2008, stored serum that had not been thawed previously was used for insulin measurements. Serum insulin was determined by metric assay (Biosource Diagnostics, Camarillo, CA)."

"Data on fasting glucose and fasting insulin levels were used to calculate the degree of insulin resistance according to the homeostasis model assessment (HOMA). The HOMA index, which is calculated by dividing the product of fasting levels of glucose and insulin by a constant, has been shown to correlate well with the euglycemic hyperinsulinemic clamp method, which is the gold standard for measuring insulin resistance."

Ethnicity Detail
All participants were residents of a suburb of Rotterdam, The Netherlands. No other information on ethnicity or race has been reported.

Screening and Diagnosis Detail
Screening Method:
CAMDEXCambridge Examination for Mental Disorders of the Elderly
GMSGeriatric Mental State Schedule (Copeland 1976)
MMSEMini-Mental State Examination (Folstein 1975)

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: DSM-III-R used for total dementia.

"The diagnosis of dementia was made following a 3-step protocol.12 Two brief tests of cognition (Mini- Mental State Examination13 and Geriatric Mental State schedule14 organic level) were used to screen all subjects. Participants with screen-positive results (Mini-Mental State Examination score <26 or Geriatric Mental State organic level >0) underwent the Cambridge Examination for Mental Disorders of the Elderly.15 Subjects who were suspected of having dementia were, if necessary, examined by a neuropsychologist. In addition, the total cohort was continuously monitored for incident dementia through computerized linkage between the study database and digitized medical records from general practitioners and the Regional Institute for Outpatient Mental Health Care.12 The diagnoses of dementia and AD were made in accordance with internationally accepted criteria for dementia (DSM-III-R),16 and AD (National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association),17 by a panel of a neurologist, neuropsychologist, and research physician."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

"We added a time-dependent covariate to the model to test the proportionality assumption. Because this assumption was violated, we performed the analyses in 3 different strata according to follow-up time: 1) short follow-up (maximum 3 years), 2) medium follow-up (3–5.5 years), and 3) long follow-up (5.5–9.7 years). Cutoffs were chosen to have approximately equal numbers of incident cases within the follow-up intervals."

This row of the table corresponds to the results obtained for 2881 subjects at risk of incident AD over the "medium follow-up" period.

AD Covariates:
Aage
Eeducation
Ggender
APOE4APOE e4 genotype
DBPdiastolic blood pressure
HDLHDL cholesterol
SBPsystolic blood pressure
TGtriglycerides
WCwaist circumference