title: Relationship of medial temporal lobe atrophy, APOE genotype, and cognitive reserve in preclinical Alzheimer's disease.
abstract: This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow-up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE-ɛ4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE-ɛ4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of Alzheimer's disease.
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Anja
authors: http://orcid.org/0000-0002-6193-0418
authors: A
authors: Soldan
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Corinne
authors: C
authors: Pettigrew
authors: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Yi
authors: Y
authors: Lu
authors: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors: Mei-Cheng
authors: MC
authors: Wang
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Ola
authors: O
authors: Selnes
authors: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Marilyn
authors: M
authors: Albert
authors: Center for Imaging Science and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors: Timothy
authors: T
authors: Brown
authors: Center for Imaging Science and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors: J Tilak
authors: JT
authors: Ratnanather
authors: Center for Imaging Science and Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA.
authors: Laurent
authors: L
authors: Younes
authors: Center for Imaging Science and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors: Michael I
authors: MI
authors: Miller
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000679:Amygdala / Q000473:pathology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy / Q000473:pathology; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D058245:Cognitive Reserve / Q000502:physiology*; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D062706:Prodromal Symptoms; D011379:Prognosis
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E
keywords: amygdala; apolipoprotein E; education; entorhinal cortex; hippocampus; mild cognitive impairment; structural MRI