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AlzRisk Paper Detail

Reference: Luchsinger, 2004
Cohort: Washington Heights-Inwood Columbia Aging Project
Risk Factor: Homocysteine

Exposure Detail
The median homocysteine level was 15.6 µmol/L (interquartile range: 10.5 to 19.7 µmol/L).

"Blood was drawn at baseline under fasting conditions. It was drawn into EDTA tubes, and centrifuged, separated into plasma aliquots, and stored at -70C within 2 hours of collection. Homocysteine and cysteine levels were measured from plasma using high performance liquid chromatography with fluorescence detection."

"The distributions of homocysteine, cysteine, vitamin B12, folate, and vitamine B6 levels were skewed and were transformed using natural logarithm to achieve normal distributions. Individuals were compared according to homocysteine categories defined by the median."

"Low" homocysteine was defined as ≤15.6 µmol/L (n=361), and "high" homocysteine was defined as >15.6 µmol/L (n=318).

Ethnicity Detail
Among the 361 participants with "low" homocysteine, 28.9% were African American, 52.9% were Hispanic and 18.1% were White.

Among the 318 participants with "high" homocysteine, 31.6% were African American, 50.7% were Hispanic and 17.8% were White.

Age Detail
The mean(± standard deviation) age of participants with "low" homocysteine was 76.4±6.9, and for those with "high" homocysteine, it was 78.0±6.6.

Screening and Diagnosis Detail
AD Diagnosis:
NINCDS ADRDA National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association Criteria (McKhann 1984)

"Diagnosis of AD was based on the National Institute of Neurologic and Cognitive Disorders and Stroke–AD and Related Disorders Association criteria.11 Diagnosis of DAS was made in all subjects with a history of stroke. Brain imaging was available in 85% of cases of stroke; in the remainder, World Health Organization criteria were used to define stroke.12 Subjects without dementia but with a history of stroke at the baseline examination were included in the analyses. These criteria and diagnostic methods have been used extensively in analysis of data in this cohort.7 Measurement of cognitive change with time. A battery of neuropsychological tests was repeated at each interval visit with a neuropsychological battery that has been validated for use in this community.8 We transformed each test into z-scores for purposes of standardization and conducted factor analyses that yielded three factors (Appendix). We added the tests with correlations of 0.5 or higher to obtain three scores: a memory score, a visuo- patialcognitive score, and a language score. The memory score included the sum of the subtests of the selective reminding test.13 Language was evaluated using the Boston Naming Test,14 the controlled word association test,15 category naming, the complex ideational material subtest, and the repetition of phrases from the Boston Diagnostic Aphasia Evaluation. Abstract reasoning was evaluated using Wechsler Adult Intelligence Scale–R similarities subtest,16 and the nonverbal identities and oddities subtest of the Mattis Dementia Rating Scale.17 Visuospatial ability was evaluated using the Rosen Drawing Test,18 and a matching version of the Benton Visual Retention Test.19"

"At baseline and each follow-up, physicians examined all subjects clinically according to a standardized protocol, trained personnel administered neuropsychological tests, and nurses collected data on family and personal history. [28]."

Covariates & Analysis Detail
Analysis Type:
Cox proportional hazards regression

"Cox proportional hazards regression was used for multivariate analyses relating quartiles of homocysteine to incident AD; the time to event variables in the models was specified as time from baseline examination to onset of dementia. Individuals with dementia not caused by the subtype of interest were censored at the time of onset of dementia."

"... We explored several models: a model with homocysteine quartiles, a model adjusting for age, a model adjusting for age and sex, and a model also adjusting for education and presence of APOE-e4 allele; all analyses were repeated including natural logarithm transformed creatinine levels."

AD Covariates:
APOE4APOE e4 genotype