TY - JOUR
T1 - Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels
AU - Babulal, Ganesh M.
AU - Ghoshal, Nupur
AU - Head, Denise
AU - Vernon, Elizabeth K.
AU - Holtzman, David M.
AU - Benzinger, Tammie L.S.
AU - Fagan, Anne M.
AU - Morris, John C.
AU - Roe, Catherine M.
N1 - Funding Information:
Funding for this study was provided by the National Institute on Aging ( R01-AG043434 , P50-AG05681 , P01-AG03991 , P01-AG026276 , and K12 HD001459 ); Fred Simmons and Olga Mohan, and the Charles and Joanne Knight Alzheimer's Research Initiative of the Washington University Knight Alzheimer's Disease Research Center (ADRC) . The authors thank the participants, investigators, and staff of the Knight ADRC Clinical Core (participant assessments), the investigators and staff of the Driving Performance In Preclinical Alzheimer's Disease study (R01-AG043434), the investigators and staff of the Biomarker Core for the Adult Children Study (P01-AG026276) for cerebrospinal fluid analysis, and the investigators and staff of the Imaging Core of the Healthy Aging and Senile Dementia study (P01-AG03991) for amyloid imaging. Imaging facilities were supported by the Washington University Institute of Clinical and Translational Sciences grant UL1-TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). Imaging analyses used the services of the Neuroimaging Informatics and Analysis Center, supported by NIH grant 5P30NS048056 .
Funding Information:
Dr. Ghoshal has participated in clinical trials of antidementia drugs sponsored by: Bristol Myers Squibb, Eli Lilly/Avid Radiopharmaceuticals, Janssen Immunotherapy, Novartis, Pfizer, Wyeth, SNIFF (The Study of Nasal Insulin to Fight Forgetfullness) study, and A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease) trial. Dr. Holtzman reports receiving research support from Eli Lilly and C2N Diagnostics smf consulting for AstraZeneca, Genentech, and Eli Lilly. He is on the Scientific Advisory Board of C2N Diagnostics and Neurophage. He co-founded and has ownership interests in C2N Diagnostics. Dr. Benzinger reports support from research grants from Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) and clinical trials involving Eli Lilly and Hoffman LaRoche. Dr. Fagan reports being on the scientific advisory boards of IBL International and Roche and is a consultant for AbbVie and Novartis. Dr. John C. Morris reports that he owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Dr. Morris has participated or is currently participating in clinical trials of antidementia drugs sponsored by the following companies: Janssen Immunotherapy, Pfizer, Eli Lilly/Avid Radiopharmaceuticals, SNIFF (The Study of Nasal Insulin to Fight Forgetfullness) study, and A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease) trial. Dr. Morris has served as a consultant for Lilly USA, ISIS Pharmaceuticals, and Charles Dana Foundation. He receives research support from Eli Lilly/Avid Radiopharmaceuticals and is funded by NIH grants P50AG005681 , P01AG003991 , P01AG026276 , and U19AG032438 .
Publisher Copyright:
© 2016 American Association for Geriatric Psychiatry
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Objectives To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. Setting Knight Alzheimer's Disease Research Center (ADRC) at Washington University (WU). Participants Participants, 65 years of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. Measurements CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p > 0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < 0.05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning. Conclusions Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults.
AB - Objectives To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. Setting Knight Alzheimer's Disease Research Center (ADRC) at Washington University (WU). Participants Participants, 65 years of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. Measurements CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p > 0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < 0.05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning. Conclusions Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults.
KW - Alzheimer disease
KW - biomarkers
KW - depression
KW - mood
KW - older adults
UR - http://www.scopus.com/inward/record.url?scp=84992188111&partnerID=8YFLogxK
U2 - 10.1016/j.jagp.2016.04.004
DO - 10.1016/j.jagp.2016.04.004
M3 - Article
C2 - 27426238
AN - SCOPUS:84992188111
SN - 1064-7481
VL - 24
SP - 1095
EP - 1104
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 11
ER -