WHITE-MATTER LESIONS AND COGNITIVE DETERIORATION IN PRESYMPTOMATIC CARRIERS OF THE AMYLOID PRECURSOR PROTEIN GENE CODON-693 MUTATION

Objective: To determine early manifestations of hereditary cerebral he morrhage with amyloidosis (Dutch). Design: Survey. Setting: Neurologic outpatient department of the University Hospital Leiden in the Nether lands. Participants: Ten presymptomatic carriers of the amyloid precur sor protein gene codon 693 mutation. Main Outcome Measurements: Extens ive neuropsychological examination and cerebral magnetic resonance ima ging. Results: Six subjects older than 40 years she-wed white matter h yperintensities on magnetic resonance imaging. Three of these six indi viduals had signs of cognitive deterioration. The four younger subject s (age, <31 years) showed no abnormalities on magnetic resonance imagi ng or on neuropsychological examination. Conclusions: We suggest that white matter hyperintensities in hereditary cerebral hemorrhage with a myloidosis (Dutch) are probably caused by chronic ischemia due to sten osis of the meningocortical arterioles, which becomes visible on magne tic resonance imaging scans in individuals who are between the ages of 30 and 40 years. The finding of cognitive deterioration in three of 1 0 presymptomatic mutation carriers supports the finding that in heredi tary cerebral hemorrhage with amyloidosis (Dutch), deterioration can o ccur without stroke. A direct relation between cognitive deterioration and white matter hyperintensities is unlikely, because only half of t he individuals with white matter hyperintensities showed signs of dete rioration.