Genetic studies on an Alzheimer Clinic population

Abstract

All patients attending the Clinic for Alzheimer Disease and Related Disorders have detailed family histories taken by a geneticist. To date, genetic histories are available for 446 consecutive, unrelated individuals. Of these, 151 (33.9%) are diagnosed as having "probable" (N = 141) or "autopsy-confirmed" (N = 10) Alzheimer disease according to recognized criteria. This data base represents a relatively unselected population with respect to more than one person in the family having dementia. Seventy-one of these 151 index cases (47.0%) have a positive family history of dementia, of which 8 (5.3%) may represent the familial (autosomal dominant) form of Alzheimer disease (FAD). Age-corrected empiric recurrence risks for Alzheimer disease/dementia were calculated for first-degree relatives of these 151 index cases using the Kaplan-Meier lifetable method.

Morbid Risk to First Degree Relatives of Neuropathologically Confirmed Cases of Alzheimer's Disease

“…Taken together, the findings of prior studies of cumula tive risk for primary dementia in the first degree relatives of AD probands arc consistent in demonstrating morbid risks ranging from approximately 39-61% [but see 23], depending on the methods employed, and the exclusion of parents from the analysis. The data generated in this series of autopsied AD probands is unique in that the variance due to uncertainty of proband diagnosis has been eliminated, and confirms a substantial familial com ponent.…”

“…The most deviant results of the application of life-table methods to estimate morbid risk for dementia are those reported by Sadovnick et al [23] and likely reflect several methodological considerations. This group excluded in dex cases whose families expressed concern regarding the possibility of familial transmission, used a highly liberal operational definition of onset, diminishing the age at which secondary cases contribute to the estimate of risk [35], and used stringent criteria for the identification and documentation of affected secondary cases.…”

“…Diag nostic certainty with respect to probands in this scries confers improved accuracy in the estimate of cumulative risk to relatives. Studies utilizing life-table methods to estimate cumulative morbid risk of relatives of clinically selected AD samples have, with few exceptions [ 12,23], produced consistent results. When calculated for parents and siblings, morbid risk has ranged from 39 to 50% by the eighth to the ninth decades [13, 16-22, 24, 34], and has been shown to be significantly greater for relatives of AD subjects than elderly controls.…”

Bipolar disorder: Evidence for a major locus

“…The model used to establish this MDS database [Sadovnick et al, 19941 was based on the internationally recognized genetic databases for multiple sclerosis (MS) and Alzheimer's disease, established at the University of British Columbia. These databases have been in operation for 13 and 8 years, respectively [Sadovnick et al, 1988[Sadovnick et al, , 1989[Sadovnick et al, , 1991a All British Columbia residents have virtually equal financial access to the MDS. When established, the MDS had 6 psychiatrists treating approximately 500 new inpatients and outpatients annually.…”

Is Dementia of the Alzheimer Type a Purely Genetic Illness? A Modelling Approach

“…In a genetic disease with an autosomal mode of inheritance, first-degree relatives of the index subject have a p = 0.5 probability of carrying the causal gene; therefore, in a sample of firstdegree relatives, the LTR is expected to be close to 50%. Most authors have found that the LTR in first-degree relatives of index DAT cases was lower than 25% [10,13,15]. Breitner and Folstein [16], using the Wein berg morbidity table found a LTR of 55.25%, but this high value could be partly due to biases [17,18].…”