Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/1/2007
Publication Date: 2/7/2007
Citation: Haan, M.N., Miller, J.W., Aiello, A.E., Whitmer, R.A., Jagust, W.J., Mungas, D.M., Allen, L.H., Green, R. 2007. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. American Journal of Clinical Nutrition. 85:511-517. Interpretive Summary: The goal of this analysis is to evaluate the association between baseline plasma homocysteine and 4.5-year incidence of a combined outcome of dementia and cognitive impairment without dementia (CIND). This is done in a population-based cohort study of Mexican Americans aged 60 and older recruited in 1998-99. Subjects and Methods. Population. The analysis presented here is based on an ongoing cohort study (n=1779) of older (60 to 100) Latinos who are primarily Mexican American and were residing in the Sacramento Valley of California in 1997-99. Details of the recruitment and baseline assessment and the protocols for diagnosing baseline dementia and CIND have been published elsewhere(14),(15). Informed consent procedures were followed and approved by both University of California, Davis and the University of Michigan, Institutional Review Boards. Diagnosis. After baseline assessment, the cognitive screening protocol required that any participant should be referred for clinical evaluation who declined from the baseline score by more than 3 points (standard error of measurement) on the Verbal Episodic Memory (VEM) test or by more than 8 points on the Modified Minimental State Exam (3MSE) (16), or whose current 3MSE or VEM score was <20th percentile on either test. These individuals underwent an expanded neuropsychological test battery and a clinical examination by a geriatrician. Case adjudication was done by an expert panel including a neurologist, a geriatrician and a neuropsychologist. Dementia and CIND cases were referred for MRI for use in assigning etiology. Cases were classified as demented if they failed one or more cognitive tests on the battery (including one memory test) at the 10th percentile, were limited in daily independent function as measured by the IQCODE, a standard interview done with informants (17) and were judged by the expert panel to meet DSM IV criteria for dementia. They were diagnosed as CIND if they failed (<10%) one additional cognitive test battery after screening but did not meet criteria for dementia, usually because of impairment in only one cognitive domain or non-memory multi-domain impairment that was judged by the review panel as clinically questionable or insignificant. Ten (10) dementia cases that were not previously diagnosed by the study were identified from a mortality search that obtained multiple causes from death certificates. These were assigned a diagnosis of dementia after case review by the same panel and the year of death was given as the year of diagnosis.
Technical Abstract: Background: Folic acid supplementation reduces homocysteine (HCY). Recent studies have linked elevated homocysteine (HCY) to an increased risk of Alzheimer’s disease, dementia, cognitive decline and underlying brain pathology, independently of B vitamins. Objective: To evaluate the association between homocysteine and the incidence of dementia and CIND. Design: The associations of baseline plasma homocysteine, erythrocyte folate, and plasma B12 with 4.5 year incidence of combined dementia and cognitive impairment not dementia (CIND) were examined in an ongoing cohort of 1,779 Mexican Americans. New cases of dementia/ CIND were ascertained by neuropsychological, clinical exams and expert adjudication. The association between HCY and dementia/CIND incidence was examined using a series of proportional hazards models. Results:HCY (log) was associated with an increased risk of dementia/CIND: (HR: 2.13, 95% CI: 1.07-4.44). Simultaneous adjustment for plasma B12, red blood cell folate, renal function, stroke, age, education, gender, country of birth, and vitamin use did not influence this association. Exclusion of participants with stroke at baseline did not affect these associations. Those in the middle tertile of plasma B12 (340 pg/mL to <498 pg/mL) were at significantly lower risk for dementia/CIND (HR: 0.40, 95% CI: 0.22-0.76, p=0.005) compared to those in the highest B12 tertile (=> 498 pg/mL) and compared to the lowest tertile (HR: 1.62: 95% CI: 0.88-3.01). Conclusions: HCY is a significant risk factor for combined dementia and cognitive impairment independent of B vitamins. Plasma B12 appears to have an inverted u-shaped association with dementia/CIND.