TY - JOUR
T1 - Brain Regional Glucose Metabolism, Neuropsychiatric Symptoms, and the Risk of Incident Mild Cognitive Impairment
T2 - The Mayo Clinic Study of Aging
AU - Krell-Roesch, Janina
AU - Syrjanen, Jeremy A.
AU - Vassilaki, Maria
AU - Lowe, Val J.
AU - Vemuri, Prashanthi
AU - Mielke, Michelle M.
AU - Machulda, Mary M.
AU - Stokin, Gorazd B.
AU - Christianson, Teresa J.
AU - Kremers, Walter K.
AU - Jack, Clifford R.
AU - Knopman, David S.
AU - Petersen, Ronald C.
AU - Geda, Yonas E.
N1 - Funding Information:
Support for this research was provided by NIH grants: National Institute on Aging (R01 AG057708; U01 AG006786; P50 AG016574; R01 AG034676; R01 AG011378; R01 AG041851), National Institute of Mental Health (K01 MH068351), and National Institute of Neurological Disorders and Stroke (R01 NS097495). This project was also supported by the Robert Wood Johnson Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the GHR Foundation, the Mayo Foundation for Medical Education and Research, Project LQ1605 from the National Program of Sustainability II (MEYS CR), the Edli Foundation and the Arizona Alzheimer's Consortium. MV receives research funding from NIH, Roche, and Biogen. VJL serves on scientific advisory boards for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research, and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and NIH. PV receives funding from NIH. MMMi has consulted for Eli Lilly and Lysosomal Therapeutics, Inc. and receives unrestricted research grants from Biogen, and Lundbeck, and research funding from NIH and the Department of Defense. MMMa receives research funding from NIH. WKK receives research funding from the Department of Defense, NIH, Astra Zeneca, Biogen, and Roche. CRJ serves on scientific advisory board for Eli Lilly, and IDSMB for Roche. But, he receives no compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. DSK serves on a Data Safety Monitoring Board for the DIAN study. He is an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen, and the Alzheimer's Treatment and Research Institute at USC, and receives research support from NIH. RCP is a consultant for Roche, Biogen, Merck, Eli Lilly, and Genentech. He receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003) and research support from NIH. YEG receives funding from NIH and Roche, and served on Lundbeck Advisory Board. JKR, JAS, GBS, and TJC report no disclosures.
Funding Information:
Support for this research was provided by NIH grants: National Institute on Aging ( R01 AG057708 ; U01 AG006786 ; P50 AG016574 ; R01 AG034676 ; R01 AG011378 ; R01 AG041851 ), National Institute of Mental Health ( K01 MH068351 ), and National Institute of Neurological Disorders and Stroke ( R01 NS097495 ). This project was also supported by the Robert Wood Johnson Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the GHR Foundation, the Mayo Foundation for Medical Education and Research, Project LQ1605 from the National Program of Sustainability II (MEYS CR), the Edli Foundation and the Arizona Alzheimer's Consortium.
Publisher Copyright:
© 2020 American Association for Geriatric Psychiatry
PY - 2021/2
Y1 - 2021/2
N2 - Objective: The authors conducted a prospective cohort study to examine the risk of incident mild cognitive impairment (MCI) as predicted by baseline neuropsychiatric symptoms (NPS) and brain regional glucose metabolic dysfunction. Methods: About 1,363 cognitively unimpaired individuals (52.8% males) aged ≥50 years were followed for a median of 4.8 years to the outcome of incident MCI. NPS were assessed using Beck Depression and Anxiety Inventories and Neuropsychiatric Inventory Questionnaire. Glucose hypometabolism was measured by fluorodeoxyglucose positron emission tomography and defined as standardized uptake value ratio ≤ 1.47 in regions typically affected in Alzheimer disease. Cox proportional hazards models were adjusted for age, sex, education, and APOE ε4 status. Results: Participants with regional glucose hypometabolism and depression (Beck Depression Inventory-II ≥13) had a more than threefold increased risk of incident MCI (hazard ratio [95% confidence interval], 3.66 [1.75, 7.65], p <0.001, χ2 = 11.83, degree of freedom [df] = 1) as compared to the reference group (normal regional glucose metabolism and no depression), and the risk was also significantly elevated (7.21 [3.54, 14.7], p <0.001, χ2 = 29.68, df = 1) for participants with glucose hypometabolism and anxiety (Beck Anxiety Inventory ≥10). Having glucose hypometabolism and ≥1 NPS (3.74 [2.40, 5.82], p <0.001, χ2 = 34.13, df = 1) or ≥2 NPS (3.89 [2.20, 6.86], p <0.001, χ2 = 21.92, df = 1) increased the risk of incident MCI by more than three times, and having ≥3 NPS increased the risk by more than four times (4.12 [2.03, 8.37], p <0.001, χ2 = 15.39, df = 1). Conclusion: Combined presence of NPS with regional glucose hypometabolism is associated with an increased risk of incident MCI, with fluorodeoxyglucose positron emission tomography appearing to be a stronger driving force of cognitive decline than NPS.
AB - Objective: The authors conducted a prospective cohort study to examine the risk of incident mild cognitive impairment (MCI) as predicted by baseline neuropsychiatric symptoms (NPS) and brain regional glucose metabolic dysfunction. Methods: About 1,363 cognitively unimpaired individuals (52.8% males) aged ≥50 years were followed for a median of 4.8 years to the outcome of incident MCI. NPS were assessed using Beck Depression and Anxiety Inventories and Neuropsychiatric Inventory Questionnaire. Glucose hypometabolism was measured by fluorodeoxyglucose positron emission tomography and defined as standardized uptake value ratio ≤ 1.47 in regions typically affected in Alzheimer disease. Cox proportional hazards models were adjusted for age, sex, education, and APOE ε4 status. Results: Participants with regional glucose hypometabolism and depression (Beck Depression Inventory-II ≥13) had a more than threefold increased risk of incident MCI (hazard ratio [95% confidence interval], 3.66 [1.75, 7.65], p <0.001, χ2 = 11.83, degree of freedom [df] = 1) as compared to the reference group (normal regional glucose metabolism and no depression), and the risk was also significantly elevated (7.21 [3.54, 14.7], p <0.001, χ2 = 29.68, df = 1) for participants with glucose hypometabolism and anxiety (Beck Anxiety Inventory ≥10). Having glucose hypometabolism and ≥1 NPS (3.74 [2.40, 5.82], p <0.001, χ2 = 34.13, df = 1) or ≥2 NPS (3.89 [2.20, 6.86], p <0.001, χ2 = 21.92, df = 1) increased the risk of incident MCI by more than three times, and having ≥3 NPS increased the risk by more than four times (4.12 [2.03, 8.37], p <0.001, χ2 = 15.39, df = 1). Conclusion: Combined presence of NPS with regional glucose hypometabolism is associated with an increased risk of incident MCI, with fluorodeoxyglucose positron emission tomography appearing to be a stronger driving force of cognitive decline than NPS.
KW - Alzheimer Disease
KW - FDG-PET
KW - Neuropsychiatric symptoms
KW - mild cognitive impairment
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U2 - 10.1016/j.jagp.2020.06.006
DO - 10.1016/j.jagp.2020.06.006
M3 - Article
C2 - 32646634
AN - SCOPUS:85087413350
SN - 1064-7481
VL - 29
SP - 179
EP - 191
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 2
ER -