CLINICAL AND NEUROPSYCHOLOGICAL CHARACTERISTICS IN FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE - RELATION TO APOLIPOPROTEIN-E POLYMORPHISM

Alzheimer's disease (AD) is a heterogeneous entity presenting as spora dic and familial disease. In familial AD, there is evidence for geneti c linkage to a yet undefined gene on chromosome 14 in early-onset pedi grees and on chromosome 19 in late-onset pedigrees. In a few early-ons et kindreds, there were mutations in the amyloid precursor gene on chr omosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon 4 allele in patients with late-onset AD. We studied the clini cal presentation and profile of cognitive deficits in 58 AD patients a t the early stage of the disease. We divided the AD patients into subg roups of sporadic late-onset (SLO) (greater than or equal to 65 years) , familial late-onset (FLO) (greater than or equal to 65 years), spora dic early-onset (SEO) (<65 years), and familial early-onset (FEO) (<65 Sears) patients and into three subgroups according to their ApoE geno type zero epsilon 4, one epsilon 4, and two epsilon 4 alleles. The AD subgroups did not differ in the global clinical severity of dementia o r the duration of the disease. SLO, FLO, SEO, and FEO subgroups did no t differ in clinical characteristics such as occurrence of rigidity, h ypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, la nguage, visuospatial, executive, and praxic functions. The epsilon 4 a llele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of on set. Patients with two epsilon 4 alleles had earlier age at onset of d ementia than those with no epsilon 4 allele (63 +/- 9 versus 68 +/- 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 all eles had lowest scores on memory tests and differ ed significantly fro m those with one or zero epsilon 4 allele in the delayed list learning (p < 0.05) and from those with zero epsilon 4 allele in the immediate and delayed story recall. In contrast, verbal functions were better p reserved in two epsilon 4 patients than in those with other ApoE genot ypes. This study failed to confirm the earlier reports of severe aphas ia, agnosia, and apraxia in familial AD patients, but the clinical phe notype was similar irrespective to the familial aggregation. However, AD patients with two epsilon 4 alleles are characterized by more sever e memory loss and earlier age of onset than those without the epsilon 4 allele.