Linguistic Performance in Vascular Dementia (original) (raw)

2010, Alzheimer's & Dementia

Background: Presenilin 1 (PSEN1) gene mutations are known to affect the clinical phenotype in relation to the age at onset and neurological signs of Alzheimer's disease (AD). Methods: Clinical data for this study were obtained by reviewing the records provided by the subjects' neurologists. Genetic analysis was carried out on DNA extracted from postmortem brain tissue. We present a novel family in which five of eight siblings had dementia. Results: Variable amounts of clinical information is available on three of the affected siblings (1 male, the proband, and 2 females) who had onset of dementia at ages 44y, 58y, and 60y, respectively. Their father had dementia in his 40s and died in his 50s. The proband presented with deficits of recent memory and inability to follow complex instructions, which appeared to have led to the loss of several jobs. At the age of 49, the proband underwent a brain MRI and EEG, which showed mild atrophy and diffuse background rhythm slowing, respectively. Memory deficits became more severe and he became progressively apathetic, confused, and impulsive. His sleep pattern changed and he presented with paranoia. He died at age 63y. The proband's elder sister presented with dementia at age 60y. She died at age 68y. The proband's younger sister sustained a head trauma when falling down a flight of stairs at the age of 55y. Subsequent to that event, she experienced intermittent headaches, memory loss, and attention and visuo-spacial deficits. She died at age 67y. Genetic analyses on all three siblings revealed a single nucleotide (T to G) substitution in codon 105 of PSEN1 resulting in a leucine for phenalanine amino acid change (F105L). Analysis of the Apolipoprotein E (ApoE) gene revealed e3/3, 32/3 and 32/3, respectively. Neuropathologically, all three met the NIA-Reagan criteria for high likelihood AD. Conclusions: We describe a new family in which some members are affected with early-onset AD associated with the F105L PSEN1 mutation. Remarkably, two subjects that carry an ApoE 32 allele developed the disease at a more advanced age than the proband that did not have that allele. Whether this represents a protective role of ApoE 32 allele is unknown.