Variant Alzheimer's disease with spastic paraparesis - Clinical characterization

Objective: To present the clinical, neuroimaging, and electrophysiologic ch aracteristics of a variant AD phenotype. Background: The authors have ident ified a large Finnish kindred with presenile dementia and spastic parapares is due to deletion of exon 9 of presenilin 1. Neuropathologic analysis show ed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyl oid peptide but lacking congophilic cores. Patients and Methods: Twenty-two affected individuals (16 men and 6 women) were identified in four successi ve generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine dec eased patients were evaluated. Electrophysiologic investigations were avail able in eight cases. CT or MRI of the head had been performed on 11 patient s and PET was performed on three patients. Result: The mean age at onset (/-SD) was 50.9 +/- 5.2 years (range 40 to 61 years). Memory impairment was present in all patients. Memory impairment appeared simultaneously with or was preceded by walking difficulty due to spasticity of the lower extremiti es (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14 ) in some patients suggested cerebellar involvement. EEG showed intermitten t generalized delta-theta activity. Head MRI showed temporal and hippocampa l atrophy; PET showed bilateral temporo-parietal hypometabolism. Conclusion : Spastic paraparesis or brisk stretch reflexes of lower extremities or clu msiness of hands combined with dementia suggests this variant of AD.