title: Clinical findings in nondemented mutation carriers predisposed to Alzheimer's disease: a model of mild cognitive impairment.
abstract: Individuals carrying a mutation associated with Alzheimer's disease (AD) may serve as a model of mild cognitive impairment (MCI). Nondemented individuals from these families can be subdivided into asymptomatic and symptomatic groups. Four families were studied. Two families are associated with APP mutations (KN670/671ML, E693G) and two with PS1 mutation (M146V, H163Y). Clinical symptoms, level of global cognitive functioning as evaluated by Mini-Mental State Examination, neuropsychological test results, neuroradiological examinations (magnetic resonance imaging (MRI) and single-photon emission tomography (SPECT)), as well as cerebrospinal fluid (CSF) measurements of tau and beta-amyloid are reported. Nondemented mutation carriers did not report any symptoms indicating cognitive decline. In addition, no clinical signs of dementia or marked cognitive impairment in neuropsychological tests were found. A reduction of temporal blood flow with SPECT was indicated in 5/13 nondemented mutation carriers. Two of these 13 individuals had moderate hyperintensities in deep white matter as observed on MRI. CSF measurements of A beta 42/43 were inconclusive because of large biological variation. A nonsignificant elevation of tau was detected in mutation carriers. In conclusion, clinical examinations of relatively young individuals carrying an AD mutation did not reveal any marked abnormalities before the clinical onset of dementia.
authors.affiliation: Division of Clinical Geriatrics and Experimental Geriatrics, Department of Neurotec, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. ove.almqvist@neurotec.ki.se
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.forename: Karin
authors.initials: K
authors.lastname: Axelman
authors.forename: Hans
authors.initials: H
authors.lastname: Basun
authors.forename: Malene
authors.initials: M
authors.lastname: Jensen
authors.forename: Matti
authors.initials: M
authors.lastname: Viitanen
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D018450:Disease Progression; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D053764:Presenilin-1; D013548:Sweden / Q000453:epidemiology; D013702:Temporal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins