title: Early onset APOE E4-negative Alzheimer's disease patients show faster cognitive decline on non-memory domains.
abstract: Age at onset and APOE E4-genotype have been shown to influence clinical manifestation of Alzheimer's disease (AD). We investigated rate of decline in specific cognitive domains according to age at onset and APOE E4-genotype in patients with AD. 199 patients with probable AD underwent at least two annual neuropsychological assessments. Patients were classified according to age-at-onset (≤ 65 years vs >65 years) and APOE genotype (positive vs negative). The neuropsychological test battery compromised tests for memory, language, attention, executive and visuo-spatial functioning. For each domain compound z-scores were calculated, based on the baseline performance of patients. Average duration of follow-up was 1.5 ± 1 years. We used linear mixed models (LMM) to estimate effects of age, APOE and age⁎APOE on cognitive decline over time. At baseline, patients were 65 ± 8 years, 98(49%) were female and MMSE was 22 ± 4. LMM showed that early onset patients declined faster on executive functioning (β ± SE:-0.09 ± 0.06) than late onset patients, but age was not related to decline in the other cognitive domains. APOE E4 negative patients declined faster on language than APOE E4 positive patients (β ± SE:-0.1 ± 0.06). When we took age and APOE genotype into account simultaneously, we found that compared to late onset-E4 positive patients, early onset-E4 negative patients declined faster on language (β ± SE:-0.36 ± 0.1), attention (β ± SE:-0.42 ± 0.1), executive (β ± SE:-0.41 ± 0.1) and visuo-spatial functioning (β ± SE:-0.43 ± 0.1). Late onset-E4 negative and early onset-E4 positive patients showed intermediate rates of decline. We found no differences in decline on memory. We found that patients who develop AD despite absence of the two most important risk factors, show steepest cognitive decline on non-memory cognitive domains.
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: l.smits@vumc.nl.
authors.forename: Lieke L
authors.initials: LL
authors.lastname: Smits
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annelies E
authors.initials: AE
authors.lastname: van der Vlies
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Esther L G E
authors.initials: EL
authors.lastname: Koedam
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Femke H
authors.initials: FH
authors.lastname: Bouwman
authors.affiliation: Alzheimer Center and Departments of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ilona E W
authors.initials: IE
authors.lastname: Reuling
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Alzheimer Center and Departments of Neurology, VU University Medical Center, Amsterdam, The Netherlands; Alzheimer Center and Departments of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: wm.vdflier@vumc.nl.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics*; D053318:Apolipoprotein E3 / Q000235:genetics*; D001288:Attention; D003072:Cognition Disorders / Q000209:etiology*; D056344:Executive Function; D005260:Female; D006801:Humans; D007802:Language; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D013028:Space Perception
chemical_list: D053318:Apolipoprotein E3; C049579:apolipoprotein E7, human
keywords: Alzheimer׳s disease; cognitive decline; cognitive neuropsychology in dementia; longitudinal design; neuropsychology