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AlzRisk Paper Detail

Reference: Tan, 2007
Cohort: Framingham Heart Study
Risk Factor: Inflammatory Biomarkers

Average Follow-up Time Detail
Follow up time ranged from 4 to 10 years.

Exposure Detail
Serum CRP levels were categorized into groups: low (0), intermediate (1 to 2 mg/L), or high (>3 mg/L).

The assay differed by exam cycle. For cycle 22, "CRP was measured with an immunoprecipitation assay (IncStar). The interassay variability was <10% and the intraassay variability was <5% for both inflammatory markers.” For cycle 16, CRP was “measured with an ultrasensitive enzyme immunoassay using monospecific polyclonal and monoclonal antibodies produced by immunization with highly purified CRP.”

Ethnicity Detail
No race or ethnicity information was provided.

Screening and Diagnosis Detail
Screening Method:
MMSEMini-Mental State Examination (Folstein 1975)

AD Diagnosis:
Brain Imaging
Medical History
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)
Neurologic examination
Neuropsychological examination

Dementia evaluation: "The methods used for dementia screening and follow-up by the Framingham dementia study have previously been described.11 Briefly, surviving cohort members who attended biennial examination cycles 14 and 15 were given a standardized neuropsychological test battery to establish a dementia-free cohort. Beginning at examination cycle 17 (1982), the Mini-Mental State Examination (MMSE)12 was administered biennially to the cohort. An MMSE score below the education-specific cutoff score, a decline of 3 or more points on subsequent administrations, or a decline of more than 5 points as compared with any previous examination prompted more in-depth testing.13 For each case of possible dementia, neurologic and neuropsychological examinations were performed. A panel consisting of at least one neurologist and a neuropsychologist reviewed cases designated as moderate or severe dementia (Clinical Dementia Rating [CDR]14 greater than or equal to 1) by the examining neurologists. Mild dementia cases (CDR = 0.5) were reexamined within 1 or 2 years and reassessed, at least biennially for the onset of moderate to severe dementia. We used data from the neurologist's examination, neuropsychological test performance, Framingham study records, hospital records, information from primary care physicians, CT and MRI records, and autopsy confirmation when available. All subjects identified to have dementia satisfied the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders criteria15 and had dementia of severity greater than or equal to 1 on the CDR scale, and had symptoms of dementia for a period of at least 6 months. All subjects identified as having Alzheimer dementia meet the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association16 criteria for definite, probable, or possible AD."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

AD Covariates:
APOE4APOE e4 genotype
BMIbody mass index
HCYplasma homocysteine
SMsmoking status
SHstroke history

Educational achievement was "dichotomized at high school completion."