Memory for new information as a cognitive marker of liability to Alzheimer's disease in a high risk group: a research note

BACKGROUND: The development of Alzheimer's disease (AD) is often insidious and there is evidence that pre-morbid neuropsychological deficits exist. OBJECTIVES: To examine aspects of neuropsychological performance as cognitive markers in a group at high risk of developing AD. METHODS: Memory for novel information and verbal fluency were examined in 33 unaffected biological siblings of patients who fulfilled criteria for probable AD, and 22 controls who reported no family history of dementia. RESULTS: Comparisons between siblings and controls revealed significant differences on overall memory performance. This was also the case when siblings were grouped according to whether or not they possessed the apoE epsilon 4 allele. There were no significant differences between siblings and controls on verbal fluency measures. CONCLUSIONS: Detailed measures of memory performance may be clinically useful in groups at a high risk of developing AD. However, further longitudinal research in such high-risk groups is needed before conclusions can be made with confidence

Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer\u27s disease.

We performed an affected sib-pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late-onset Alzheimer\u27s disease (AD) in a sample comprising 428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD = 3.62), and was strongest in pairs with high mean AAO (\u3e80). A similar effect was observed on chromosome 2q in the NIMH sample (max LOD = 2.73); this region was not typed in the IADC/UK sample. Suggestive evidence was observed in the combined sample of linkage of AAO difference to chromosome 19q (max LOD = 2.33) in the vicinity of APOE and 12p (max LOD = 2.22), with linkage strongest in sib-pairs with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q in the whole sample (max LOD = 2.29), with the effect strongest in the NIMH sample (max LOD = 3.58), and in pairs with high mean ROD. Additional suggestive evidence was also observed in the NIMH sample with AAO difference on chromosome 6p (max LOD = 2.44) and 15p (max LOD = 1.87), with linkage strongest in pairs with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD = 2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive evidence of increased identical by descent (IBD) in APOE epsilon4 homozygotes on chromosome 1 (max LOD = 3.08) and chromosome 9 (max LOD = 3.34). The previously reported genome-wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied