Premium
PL‐02‐01: Intergenerational Studies of Dementia Risk
Author(s) -
Wolf Philip A.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.241
Subject(s) - dementia , disease , family history , medicine , framingham heart study , cohort , concordance , risk factor , population , apolipoprotein e , cohort study , alzheimer's disease , gerontology , pediatrics , psychology , framingham risk score , environmental health
Background: First-degree relatives of patients with Alzheimer disease (AD) develop the disease at higher rates than unrelated individuals. Apart from dominantly inherited early-onset AD the sole genetic susceptibility factor for AD is the Apolipoprotein E (ApoEe4) allele which is neither necessary nor sufficient to cause disease. Family history studies show the familial risk for AD is approximately four times greater than that for the general population. Risk appears to increase with the number of affected first-degree relatives, particularly if the mother is affected. A tendency for a high concordance rate exists in identical twins with AD. The pathological processes leading to AD are underway for many years, probably decades prior to overt evidence of clinical disease. Identification of persons at high risk of AD is essential for a better understanding of the pathophysiology and for development of preventive and therapeutic interventions. Methods: In the Framingham Heart Study the study of AD and dementia has been underway for more than 30 years. Beginning in 1976 a dementia-free cohort was established among the Original cohort. These 3,042 subjects have been followed with a two-yearly MMSE & with intensive surveillance of all medical contacts and hospitalizations for the development of cognitive decline and dementia. Results: As of 2008, 507 subjects developed dementia, 384 fulfilled ADRDA criteria for AD. Through a brain donation program, over 130 brains have been studied and AD usually confirmed neuropathologically. Thus we have a large number of subjects fulfilling criteria for AD and didn’t have to rely on a family history. The children of these subjects, with and without dementia or AD have been studied with two successive quantitative brain MR scans and neuropsychological testing. A significant interaction was seen with ApoEe4 status and parental dementia. In ApoEe4carriers, parental AD was associated with poorer scores on tests of verbal and visual memory. Conclusions: On preliminary study, no significant association with brain volumes was seen though serial MR scans tended to show a steeper decline in Offspring with parental AD who were also carriers of the ApoEe4 allele. Using a 550K GWAS we are seeking other associations with a variety of phenotypes for AD and dementia.