Insula and Inferior Frontal Gyrus’ Activities Protect Memory Performance Against Alzheimer’s Disease Pathology in Old Age

Article type: Research Article

Authors: Lin, Feng^{a; b; c; *} | Ren, Ping^a | Lo, Raymond Y.^d | Chapman, Benjamin P.^{b; e} | Jacobs, Alanna^{a; b} | Baran, Timothy M.^f | Porsteinsson, Anton P.^{b; g} | Foxe, John J.^h | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] School of Nursing, University of Rochester Medical Center, Rochester, NY, USA | [b] Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA | [c] Department of Brain and Cognitive Science, University of Rochester, Rochester, NY, USA | [d] Department of Neurology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Taiwan, Taipai | [e] Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, USA | [f] Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA | [g] Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA | [h] Department of Neuroscience & The Ernest J. Del Monte Institute for Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA

Correspondence: [*] Correspondence to: Feng Lin, PhD, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. Tel.: +1 585 276 6002; E-mail: vankee_lin@urmc.rochester.edu.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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.

Keywords: Amyloid-β, apolipoprotein E ɛ4, frontal cortex, memory, mild cognitive impairment, resting state functional MRI

DOI: 10.3233/JAD-160715

Journal: Journal of Alzheimer's Disease, vol. 55, no. 2, pp. 669-678, 2017