title: Insula and Inferior Frontal Gyrus' Activities Protect Memory Performance Against Alzheimer's Disease Pathology in Old Age.
abstract: Apolipoprotein E (APOE) ɛ4 carriers and patients with amnestic mild cognitive impairment (MCI) have high risk of developing Alzheimer's disease (AD). The Scaffolding Theory of Aging and Cognition proposes that recruitment of additional frontal brain regions can protect cognition against aging. This thesis has yet to be fully tested in older adults at high risk for AD. In the present study, 75 older participants (mean age: 74 years) were included. Applying a voxel-wise approach, fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional neuroimaging data were analyzed as a function of APOEɛ4 status (carrier versus noncarrier) and clinical status (healthy control [HC] versus MCI) using a 2×2 analysis of covariance (ANCOVA). Measures of cognition and cerebrospinal fluid levels of amyloid- β were also obtained. Three frontal regions were identified with significant interaction effects using ANCOVA (corrected p < 0.01): left-insula, left-inferior frontal gyrus (IFG), and right-precentral gyrus. The HC/APOEɛ4 carrier group had significantly higher fALFF in all three regions than other groups. In the entire sample, for two regions (left insula and left IFG), a significant positive relationship between amyloid-β and memory was only observed among individuals with low fALFF. Our results suggest higher activity in frontal regions may explain being cognitively normal among a subgroup of APOEɛ4 carriers and protect against the negative impact of AD-associated pathology on memory. This is an observation with potential implications for AD therapeutics.
authors.affiliation: School of Nursing, University of Rochester Medical Center, Rochester, NY, USA.|Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.|Department of Brain and Cognitive Science, University of Rochester, Rochester, NY, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: School of Nursing, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Ren
authors.affiliation: Department of Neurology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Taiwan, Taipai.
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Lo
authors.affiliation: Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.|Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Chapman
authors.affiliation: School of Nursing, University of Rochester Medical Center, Rochester, NY, USA.|Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Alanna
authors.initials: A
authors.lastname: Jacobs
authors.affiliation: Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Baran
authors.affiliation: Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.|Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Anton P
authors.initials: AP
authors.lastname: Porsteinsson
authors.affiliation: Department of Neuroscience & The Ernest J. Del Monte Institute for Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Foxe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000502:physiology*
chemical_list: D053327:Apolipoprotein E4; D010100:Oxygen
keywords: Amyloid-β; apolipoprotein E ɛ4; frontal cortex; memory; mild cognitive impairment; resting state functional MRI