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AlzRisk Paper Detail

Reference: Seshadri, 2002
Cohort: Framingham Heart Study
Risk Factor: Homocysteine

Average Follow-up Time Detail
Participants underwent plasma homocysteine (Hcy) measurements up to two times. From the earlier measurement, the median follow-up time was about 16 years (estimated). From the more recent measurement, the median follow-up time was 8 years (range, 1 to 13 years). The entry pertains to the findings related to the earlier Hcy measurement.

Exposure Detail
This entry pertains to plasma levels of homocysteine that were measured 8 years before dementia diagnoses began (i.e., the earlier measurements). The investigators computed quartiles of the "earlier" Hcy measurements for each 5-year age group, but did not report the ranges in their paper.

"Plasma total homocysteine levels were measured in all subjects at the 20th biennial examination (baseline). An earlier measure from the 16th biennial examination (performed between 1979 and 1982, approximately eight years before baseline) was also available for 935 of the subjects (86 percent). All plasma specimens were stored at or below –20°C. Homocysteine levels were determined with the use of high-performance liquid chromatography with fluorometric detection.[27] The coefficient of variation for this assay was 9 percent.[28]"

"The 75th percentile of the plasma homocysteine level (the cutoff point for quartile 4) was 13.2 μmol per liter for subjects 65 to 69 years old, 13.8 μmol per liter for subjects 70 to 74 years old, 14.5 μmol per liter for subjects 75 to 79 years old, 16.5 μmol per liter for subjects 80 to 84 years old, 19.3 μmol per liter for subjects 85 to 89 years old, and 26.6 μmol per liter for subjects 90 to 95 years old."

Screening and Diagnosis Detail
Screening Method:
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: "The diagnosis of dementia was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition; our definition also required a duration of symptoms greater than six months, and a score for severity of dementia of 1 or higher on the clinical dementia rating scale."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

"Cox proportional hazards regression models were used to examine the relation between the homocysteine level and the incidence of dementia and Alzheimer disease during follow up, after adjustment for age (in one year increments), sex, and APOE genotype (with or without an APOE e4 allele). In supplementary analyses, we also adjusted for vitamin levels and other covariates."

AD Covariates:
APOE4APOE e4 genotype

TD Covariates:
APOE4APOE e4 genotype