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AlzRisk Paper Detail

Reference: Ronnemaa, 2009
Cohort: Uppsala Longitudinal Study of Adult Men
Risk Factor: Diabetes Mellitus

Average Follow-up Time Detail
The incident cohort was 1125 non-demented 71 year old individuals. Cognitive testing was done twice over the follow-up period: at age 77 (n = 804 returning participants), and at age 82 (n = 520).

The median follow-up time was 12 years.

Exposure Detail
The exposure was fasting plasma insulin (mU/L).

"An OGTT was performed by measuring the plasma concentrations of glucose, fasting insulin and insulin 30 and 120 min after ingestion of 75 g anhydrous dextrose. The early insulin response (EIR) was calculated as the ratio of the increment in plasma insulin to that in plasma glucose during the first 30 min of the OGTT [8]...The concentrations of proinsulin and 32–33 split proinsulin were analyzed using the two-site immunometric assay technique [14] in plasma samples that had been stored frozen (−70°C) since baseline. Insulin concentrations were also determined in these samples, using the Access Immunoassay System (Sanofi Pasteur Diagnostics; Redmond, WA, USA)."

Ethnicity Detail
No race or ethnicity information was provided in the report. According to a description of the cohort , nearly all the members of the original cohort were Caucasian.

Screening and Diagnosis Detail
Screening Method:
7MS7 Minute Screen (Solomon 1998)
MMSEMini-Mental State Examination (Folstein 1975)
TMTTrail Making Test (Reitan 1958)

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

Total dementia definition:
Defined as 'any dementia or cognitive impairment'.

The Mini Mental State Examination (MMSE), the Trail Making Test (TMT), and a Swedish version of the 7 Minute Screen (7MS) were administered as screening tests. Individuals with low scores were referred to the geriatric memory clinic for further follow-up. The MMSE and TMT were administered for screenings at ages 71 and 77, while the MMSE and the 7MS were administered for screenings at age 82.

"The original work-up of participants with diagnosed
specific dementia subtypes varied but always included a
detailed medical history, relevant neuropsychological testing, physical examination and laboratory tests to rule out other systemic or brain diseases that might account for the deficits...To standardize any differences between the original work-ups, the records of all possible cases of dementia and cognitive impairment were reviewed, and the definitive diagnoses in the present study were confirmed by two experienced geriatricians, independently of each other and blinded to the baseline data. In the event of disagreement, a third geriatrician reviewed the case and the diagnosis was determined by majority decision. Our primary endpoint, Alzheimer’s disease, was diagnosed according to the criteria of the National Institute of Neurological and Communicative Diseases and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) and the criteria from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM IV)."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

The final reported analysis adjusted for diabetes mellitus. In this study, individuals were classified as having diabetes mellitus if they had a fasting plasma glucose concentration > 7.0 mmol/l, or if they used pharmacologic treatments for diabetes. There were 121 diabetic individuals in this analysis sample.

AD Covariates:
BMIbody mass index
DMdiabetes mellitus
SMsmoking status
SBPsystolic blood pressure
TCtotal cholesterol

TD Covariates:
BMIbody mass index
DMdiabetes mellitus
SMsmoking status
SBPsystolic blood pressure
TCtotal cholesterol