Variant Alzheimer's disease with spastic paraparesis: clinical characterization.
OBJECTIVE
To present the clinical, neuroimaging, and electrophysiologic characteristics of a variant AD phenotype.


BACKGROUND
The authors have identified a large Finnish kindred with presenile dementia and spastic paraparesis due to deletion of exon 9 of presenilin 1. Neuropathologic analysis showed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyloid peptide but lacking congophilic cores.


METHODS
Twenty-two affected individuals (16 men and 6 women) were identified in four successive generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine deceased patients were evaluated. Electrophysiologic investigations were available in eight cases. CT or MRI of the head had been performed on 11 patients and PET was performed on three patients.


RESULTS
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 extremities (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14) in some patients suggested cerebellar involvement. EEG showed intermittent generalized delta-theta activity. Head MRI showed temporal and hippocampal atrophy; PET showed bilateral temporo-parietal hypometabolism.


CONCLUSIONS
Spastic paraparesis or brisk stretch reflexes of lower extremities or clumsiness of hands combined with dementia suggests this variant of AD.
Verkkoniemi
A
A
Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Finland. Aulie@DLC.fi
Somer
M
M
Rinne
J O
JO
Myllykangas
L
L
Crook
R
R
Hardy
J
J
Viitanen
M
M
Kalimo
H
H
Haltia
M
M
D017668:Age of Onset; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D020336:Paraparesis, Spastic / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D011859:Radiography; D014055:Tomography, Emission-Computed