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From the Department of Neurology (Drs. Lehtovirta, Soininen, Helkala, Hartikainen, Hanninen, and Riekkinen) and the Unit of Clinical Genetics of the Department of Gynecology and Obstetrics (Drs. Helisalmi, Mannermaa, and Ryynanen), University Hospital and University of Kuopio, Kuopio, Finland.
Supported by the Medical Research Council of the Academy of Finland.
Received January 5, 1995. Accepted in final form June 22, 1995.
Address correspondence and reprint requests to Dr. Maarit Lehtovirta, Department of Neurology, University Hospital of Kuopio, P.O. Box 1627, SF-70211 Kuopio, Finland.
Alzheimer's disease (AD) is a heterogeneous entity presenting as sporadic and familial disease.In familial AD, there is evidence for genetic linkage to a yet undefined gene on chromosome 14 in early-onset pedigrees and on chromosome 19 in late-onset pedigrees. In a few early-onset kindreds, there were mutations in the amyloid precursor gene on chromosome 21. There is an increased frequency of apolipoprotein E (ApoE) epsilon 4 allele in patients with late-onset AD. We studied the clinical presentation and profile of cognitive deficits in 58 AD patients at the early stage of the disease. We divided the AD patients into subgroups of sporadic late-onset (SLO) (more than equals to 65 years), familial late-onset (FLO) (more than equals to 65 years), sporadic early-onset (SEO) (less than 65 years), and familial early-onset (FEO) (less than 65 years) patients and into three subgroups according to their ApoE genotype zero epsilon 4, one epsilon 4, and two epsilon 4 alleles. The AD subgroups did not differ in the global clinical severity of dementia or the duration of the disease. SLO, FLO, SEO, and FEO subgroups did not differ in clinical characteristics such as occurrence of rigidity, hypokinesia, tremor, myoclonus, hallucinations, delusions, or epileptic seizures nor in the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions. The epsilon 4 allele frequency was 0.43 for all AD patients and did not differ across subgroups divided according to the familial aggregation and age of onset. Patients with two epsilon 4 alleles had earlier age at onset of dementia than those with no epsilon 4 allele (63 plus minus 9 versus 68 plus minus 9 years), but otherwise the clinical symptoms and signs were not related to the ApoE genotype. However, the AD patients with two epsilon 4 alleles had lowest scores on memory tests and differed significantly from those with one or zero epsilon 4 allele in the delayed list learning (p less than 0.05) and from those with zero epsilon 4 allele in the immediate and delayed story recall. In contrast, verbal functions were better preserved in two epsilon 4 patients than in those with other ApoE genotypes. This study failed to confirm the earlier reports of severe aphasia, agnosia, and apraxia in familial AD patients, but the clinical phenotype was similar irrespective to the familial aggregation. However, AD patients with two epsilon 4 alleles are characterized by more severe memory loss and earlier age of onset than those without the epsilon 4 allele.
NEUROLOGY 1996;46: 413-419
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