Neuropsychiatric Symptoms and Alzheimer Disease Biomarkers Independently Predict Progression to Incident Cognitive Impairment

Overview

Journal Am J Geriatr Psychiatry

Publisher Elsevier

Specialty Geriatrics

Date 2023 Aug 6

PMID 37544835

Authors

Ganesh M Babulal

Ling Chen

Samantha A Murphy

Jason M Doherty

Ann M Johnson

John C Morris

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate the effect of neuropsychiatric symptoms and depression symptoms, respectively, and Alzheimer disease (AD) biomarkers (cerebrospinal fluid [CSF] or Positron Emission Tomography [PET] imaging) on the progression to incident cognitive impairment among cognitively normal older adults.

Design: Prospective, observation, longitudinal study.

Setting: Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine.

Participants: Older adults aged 65 and above who participated in AD longitudinal studies (n = 286).

Measurements: CSF and PET biomarkers, Clinical Dementia Rating (CDR), Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q).

Results: Participants had an average follow-up of eight years, and 31 progressed from CDR 0 to CDR >0. After adjusting for sex, age, and education in the Cox proportional hazards survival models, neuropsychiatric symptoms as a time-dependent covariate was statistically significant in the three CSF (Aβ/Aβ, t-Tau/Aβ, p-Tau/Aβ) PET imaging models (HR = 1.33-1.50). The biomarkers were also significant as main effects (HR = 2.00-4.04). Change in depression symptoms was not significant in any models. The interactions between biomarkers and neuropsychiatric symptoms and depression were not statistically significant.

Conclusions: Changes in neuropsychiatric symptoms increase the risk of progression to cognitive impairment among healthy, cognitively normal adults, independent of AD biomarkers. Routine assessment of neuropsychiatric symptoms could provide valuable clinical information about cognitive functioning and preclinical disease state.

Citing Articles

Practical Assessment of Neuropsychiatric Symptoms: Updated Reliability, Validity, and Cutoffs for the Neuropsychiatric Inventory Questionnaire.

Gonzalez D, Finley J, Patel S, Soble J Am J Geriatr Psychiatry. 2024; 33(5):524-534.

PMID: 39551647 PMC: 11903187. DOI: 10.1016/j.jagp.2024.10.014.

Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms.

Frank B, Walsh M, Hurley L, Groh J, Blennow K, Zetterberg H J Alzheimers Dis. 2024; 100(3):1055-1073.

PMID: 38995786 PMC: 11805585. DOI: 10.3233/JAD-240125.

References

Morris J, Schindler S, McCue L, Moulder K, Benzinger T, Cruchaga C . Assessment of Racial Disparities in Biomarkers for Alzheimer Disease. JAMA Neurol. 2019; 76(3):264-273. PMC: 6439726. DOI: 10.1001/jamaneurol.2018.4249. View

Ruthirakuhan M, Ismail Z, Herrmann N, Gallagher D, Lanctot K . Mild behavioral impairment is associated with progression to Alzheimer's disease: A clinicopathological study. Alzheimers Dement. 2022; 18(11):2199-2208. PMC: 9339594. DOI: 10.1002/alz.12519. View

Lussier F, Pascoal T, Chamoun M, Therriault J, Tissot C, Savard M . Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals. Alzheimers Dement. 2020; 16(1):192-199. PMC: 7041633. DOI: 10.1002/alz.12007. View

Schindler S, Gray J, Gordon B, Xiong C, Batrla-Utermann R, Quan M . Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging. Alzheimers Dement. 2018; 14(11):1460-1469. PMC: 6119652. DOI: 10.1016/j.jalz.2018.01.013. View

Babulal G, Zhu Y, Trani J . Racial and ethnic differences in neuropsychiatric symptoms and progression to incident cognitive impairment among community-dwelling participants. Alzheimers Dement. 2023; 19(8):3635-3643. PMC: 10440214. DOI: 10.1002/alz.12988. View

Peters M, Schwartz S, Han D, Rabins P, Steinberg M, Tschanz J . Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's dementia and death: the Cache County Dementia Progression Study. Am J Psychiatry. 2015; 172(5):460-5. PMC: 4416978. DOI: 10.1176/appi.ajp.2014.14040480. View

Rockwood K, Strang D, Macknight C, DOWNER R, Morris J . Interrater reliability of the Clinical Dementia Rating in a multicenter trial. J Am Geriatr Soc. 2000; 48(5):558-9. DOI: 10.1111/j.1532-5415.2000.tb05004.x. View

Schindler S, Bollinger J, Ovod V, Mawuenyega K, Li Y, Gordon B . High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019; 93(17):e1647-e1659. PMC: 6946467. DOI: 10.1212/WNL.0000000000008081. View

Tsunoda K, Yamashita T, Osakada Y, Sasaki R, Tadokoro K, Matsumoto N . Early Emergence of Neuropsychiatric Symptoms in Cognitively Normal Subjects and Mild Cognitive Impairment. J Alzheimers Dis. 2019; 73(1):209-215. DOI: 10.3233/JAD-190669. View

10.

Tissot C, Therriault J, Pascoal T, Chamoun M, Lussier F, Savard M . Association between regional tau pathology and neuropsychiatric symptoms in aging and dementia due to Alzheimer's disease. Alzheimers Dement (N Y). 2021; 7(1):e12154. PMC: 8012244. DOI: 10.1002/trc2.12154. View

11.

Roe C, Ances B, Head D, Babulal G, Stout S, Grant E . Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers. Brain. 2018; 141(11):3233-3248. PMC: 6202574. DOI: 10.1093/brain/awy244. View

12.

Su Y, Flores S, Wang G, Hornbeck R, Speidel B, Joseph-Mathurin N . Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies. Alzheimers Dement (Amst). 2019; 11:180-190. PMC: 6389727. DOI: 10.1016/j.dadm.2018.12.008. View

13.

Abdoli N, Salari N, Darvishi N, Jafarpour S, Solaymani M, Mohammadi M . The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2021; 132:1067-1073. DOI: 10.1016/j.neubiorev.2021.10.041. View

14.

Storandt M, Grant E, Miller J, Morris J . Longitudinal course and neuropathologic outcomes in original vs revised MCI and in pre-MCI. Neurology. 2006; 67(3):467-73. DOI: 10.1212/01.wnl.0000228231.26111.6e. View

15.

Brookmeyer R, Abdalla N . Estimation of lifetime risks of Alzheimer's disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018; 14(8):981-988. PMC: 6097953. DOI: 10.1016/j.jalz.2018.03.005. View

16.

Yang L, Deng Y, Leng Y, Ou Y, Li Y, Chen S . Depression, Depression Treatments, and Risk of Incident Dementia: A Prospective Cohort Study of 354,313 Participants. Biol Psychiatry. 2022; 93(9):802-809. DOI: 10.1016/j.biopsych.2022.08.026. View

17.

Donovan N, Locascio J, Marshall G, Gatchel J, Hanseeuw B, Rentz D . Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults. Am J Psychiatry. 2018; 175(6):530-537. PMC: 5988933. DOI: 10.1176/appi.ajp.2017.17040442. View

18.

Fagan A, Mintun M, Mach R, Lee S, Dence C, Shah A . Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2005; 59(3):512-9. DOI: 10.1002/ana.20730. View

19.

Latalova K, Kamaradova D, Prasko J . Perspectives on perceived stigma and self-stigma in adult male patients with depression. Neuropsychiatr Dis Treat. 2014; 10:1399-405. PMC: 4122562. DOI: 10.2147/NDT.S54081. View

20.

Ghahremani M, Wang M, Chen H, Zetterberg H, Smith E, Ismail Z . Plasma Phosphorylated Tau at Threonine 181 and Neuropsychiatric Symptoms in Preclinical and Prodromal Alzheimer Disease. Neurology. 2022; 100(7):e683-e693. PMC: 9969916. DOI: 10.1212/WNL.0000000000201517. View