The Role of Amyloid, Tau, and APOE Genotype on the Relationship Between Informant-Reported Sleep Disturbance and Alzheimer’s Disease Risks
Article type: Research Article
Authors: Kim, Hyuna; b; * | Levine, Alinac | Cohen, Danielb | Gehrman, Philipd; e | Zhu, Xia; f | Devanand, Davangere P.a; b; g | Lee, Seonjooc; h | Goldberg, Terry E.a; b; i | on behalf of the Alzheimer’s Disease Neuroimaging Initiative1
Affiliations: [a] Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA | [b] Division of Geriatric Psychiatry, New York State Psychiatric Institute, NewYork, NY, USA | [c] Division of Mental Health Data Science, New York State Psychiatric Institute, New York, NY, USA | [d] Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA | [e] Mental Illness Research, Education, and Clinical Center, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA | [f] Division of Anxiety, Mood, Eating, and Related Disorder, New York State Psychiatric Institute, New York, NY, USA | [g] Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA | [h] Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA | [i] Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA
Correspondence: [*] Correspondence to: Hyun Kim, PhD, T32 Post-doctoral Fellow, Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Clinic 1501, New York, NY 10032, USA. Tel.: +1 646 774 7202; [email protected].
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data-base (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/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf>
Abstract: Background:The association between sleep and Alzheimer’s disease (AD) biomarkers are well-established, but little is known about how they interact to change the course of AD. Objective:To determine the potential interaction between sleep disturbance and Aβ, tau, and APOE4 on brain atrophy and cognitive decline. Methods:Sample included 351 participants (mean age 72.01 ± 6.67, 50.4%female) who were followed for approximately 5 years as part of the Alzheimer’s Disease Neuroimaging Initiative. Informant-reported sleep disturbance (IRSD) was measured using the Neuropsychiatric Inventory (NPI). Changes in magnetic resonance imaging (MRI)-measured AD signature brain regions and cognitive performance and IRSD’s interaction with cerebrospinal fluid amyloid-β (Aβ42) and p-Tau depositions and APOE4 status were examined using the linear mixed models. Results: Baseline IRSD was not significantly associated with the rate of atrophy after adjusting for covariates (age, sex, education, total NPI severity score, and sleep medications). However, there was a significant interaction between IRSD and AD biomarkers on faster atrophy rates in multiple brain regions, including the cortical and middle temporal volumes. Post-hoc analyses indicated that Aβ and p-Tau/Aβ predicted a faster decline in these regions/domains in IRSD, compared with biomarker-negative individuals with IRSD (ps≤0.001). There was a significant IRSD*APOE4 interaction for brain atrophy rate (ps≤0.02) but not for cognition. Conclusion:IRSD may increase the future risk of AD by contributing to faster brain atrophy and cognitive decline when combined with the presence of AD biomarkers and APOE4. Early intervention for sleep disturbance could help reduce the risk of developing AD.
Keywords: All sleep disorders, Alzheimer’s disease, cognitive aging, insomnia, volumetric MRI
DOI: 10.3233/JAD-215417
Journal: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1567-1580, 2022
