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AlzRisk Paper Detail

Reference: Eriksson, 2011
Cohort: Swedish Twin Registry
Risk Factor: Inflammatory Biomarkers

Average Follow-up Time Detail
Serum measurements were taken on average 4.3 years before dementia onset.

Samples used in this study were collected from two sources: the Swedish Twin Registry (STR), and from independent non-twin case-control Swedish AD samples from other prospective cohorts (see Reynolds CA, Hong MG, Eriksson UK, et al. (2009). A survey of ABCA1 sequence variation confirms association with dementia. Hum Mutat 30, 1348-1354).

Exposure Detail
CRP levels were determined with a high sensitivity near infrared particle immunoassay rate (NIPIA rate) method (measurement interval 0.2-380 mg/L) using Beckman reagents on Synchron LX20 automated equipment (Beckman Coulter, Fullerton, CA USA).

Authors did not provide the mean or range of the tertiles, but the geometric mean (SD) for CRP among those with AD was 1.8 (3.0) mg/L, and 2.1 (3.1) mg/L for controls.

Ethnicity Detail
Detailed information on ethnicity is not provided in the paper, but all participants were residents of Sweden.

Age Detail
The age presented in the table is a weighted average of the ages of case and controls in the nested case-control (incident) sample of this study (see Table 2 of paper).

For the larger cohort described in this paper, the average age at sampling (± SD) for controls was 77.7 ± 8.7 years and age at onset for dementia cases was 75.3 ± 8.2 years.

Screening and Diagnosis Detail
Screening Method:
Informant interview
MMSEMini-Mental State Examination (Folstein 1975)
Neuropsych Testing
TELETelephone assessment of dementia

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 and IV

The cases and controls from the STR and from the non-twin case control sample had different screening procedures, described below:

Twin sample: "In the twin samples, dementia was ascertained through a two-step procedure which entailed, first, a cognitive screening and, second, diagnostic assessment of each suspected case. In brief, the Mini Mental State Examination (MMSE) [13] or, if by telephone, the TELE [14] was used to screen for cognitive dysfunction. Twins who screened positive for suspicion of dementia (and their twin partners) were further evaluated through cognitive testing, physical and neurological examinations, informant interviews, reviews of medical records, and laboratory tests. Final diagnoses of dementia were set at a multidisciplinary consensus conference. Dementia was diagnosed according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders versions III-R [15] and IV [16] and differentially diagnosed as possible or probable (71%) AD(NINCDS/ADRDA criteria) [17], vascular dementia (NINDS-AIREN criteria) [18], mixed dementia (VaD + AD), other specified dementia, or unspecified dementia."

Swedish non-two case-control sample: "All clinically diagnosed AD patients underwent a thorough investigation, which included a medical history, physical, neurological and psychiatric examination, screening laboratory tests, ECG, X-ray of the chest, EEG, and computerized tomography (CT) of the brain. MMSE was administered by a trained nurse and recorded in journals. Clinical AD diagnoses were made according to the NINCDS-ADRDA criteria. All neuropathologically diagnosed AD patients also fulfilled the clinical NINCDS-criteria for probable AD and met the neuropathological CERAD criteria for definitive AD. Among controls, 140 were healthy volunteers without history, symptoms or signs of psychiatric or neurological disease, malignant disease, or systemic disorders. There were 108 autopsy controls consisting of patients who had died from cardiac disease or malignant disease and whose medical records revealed no history of dementia or other psychiatric or neurological diseases. Postmortem examination revealed no macroscopic infarcts."

Covariates & Analysis Detail
Analysis Type:
Conditional logistic regression

Quantile cutoffs were based on the marker distribution in the control groups. Non-normally distributed variables were log-transformed.

AD Covariates:
APOE4APOE e4 genotype
BMIbody mass index
CHDcoronary heart disease
DMdiabetes mellitus
DBPdiastolic blood pressure
SMsmoking status
SHstroke history
SBPsystolic blood pressure

Age and gender were matched by design of the study. Additional adjustment for APOE4, BMI, smoking, blood pressure, education, diabetes, CHD and stroke did not change the results.