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Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults.
J Alzheimers Dis. 2017; 60(4):1451-1459.JA

Abstract

BACKGROUND

Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages.

OBJECTIVE

To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults.

METHODS

84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1-42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models.

RESULTS

14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score.

CONCLUSIONS

Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.

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Authors+Show Affiliations

Dumurgier J
Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA. INSERM U942 and Memory Clinical Center, Saint Louis - Lariboisiere - Fernand Widal Hospital, AP-HP, University Paris VII Denis Diderot, Paris, France.
Hanseeuw BJ
Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
Hatling FB
Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
Judge KA
Department of Radiology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA. Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
Schultz AP
Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
Chhatwal JP
Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
Blacker D
Department of Psychiatry, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
Sperling RA
Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
Johnson KA
Department of Radiology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
Hyman BT
Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.
Gómez-Isla T
Department of Neurology, Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA.

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrainCognitionFemaleFollow-Up StudiesHumansLinear ModelsLongitudinal StudiesMagnetic Resonance ImagingMaleOrgan SizePeptide FragmentsPhosphorylationPositron-Emission TomographyPrognosisProportional Hazards ModelsRisk Factorstau Proteins

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29036824

Citation

Dumurgier, Julien, et al. "Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults." Journal of Alzheimer's Disease : JAD, vol. 60, no. 4, 2017, pp. 1451-1459.
Dumurgier J, Hanseeuw BJ, Hatling FB, et al. Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. J Alzheimers Dis. 2017;60(4):1451-1459.
Dumurgier, J., Hanseeuw, B. J., Hatling, F. B., Judge, K. A., Schultz, A. P., Chhatwal, J. P., Blacker, D., Sperling, R. A., Johnson, K. A., Hyman, B. T., & Gómez-Isla, T. (2017). Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. Journal of Alzheimer's Disease : JAD, 60(4), 1451-1459. https://doi.org/10.3233/JAD-170511
Dumurgier J, et al. Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. J Alzheimers Dis. 2017;60(4):1451-1459. PubMed PMID: 29036824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. AU - Dumurgier,Julien, AU - Hanseeuw,Bernard J, AU - Hatling,Frances B, AU - Judge,Kelly A, AU - Schultz,Aaron P, AU - Chhatwal,Jasmeer P, AU - Blacker,Deborah, AU - Sperling,Reisa A, AU - Johnson,Keith A, AU - Hyman,Bradley T, AU - Gómez-Isla,Teresa, PY - 2017/10/19/pubmed PY - 2018/7/24/medline PY - 2017/10/18/entrez KW - Biomarkers KW - cerebrospinal fluid KW - cognitive decline KW - epidemiology KW - neuroimaging SP - 1451 EP - 1459 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 60 IS - 4 N2 - BACKGROUND: Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages. OBJECTIVE: To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults. METHODS: 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1-42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models. RESULTS: 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score. CONCLUSIONS: Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/29036824/Alzheimer's_Disease_Biomarkers_and_Future_Decline_in_Cognitive_Normal_Older_Adults_ DB - PRIME DP - Unbound Medicine ER -