Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016;3(2):92-100.
doi: 10.14283/jpad.2016.90.

Longitudinal Trajectories of Clinical Decline in Amyloid Positive and Negative Populations

P T Trzepacz  1 , H Hochstetler, S Wang, P Yu, M Case, D B Henley, E Degenhardt, J-M Leoutsakos, C G Lyketsos
Affiliations

Longitudinal Trajectories of Clinical Decline in Amyloid Positive and Negative Populations

P T Trzepacz et al. J Prev Alzheimers Dis. 2016.

Abstract

Background: Brain beta-amyloid status portends different trajectories of clinical decline.

Objective: Determine trajectories and predictive baseline variable(s).

Design: Longitudinal, up to 24 months.

Setting: ADNI sites.

Participants: Healthy control (n=325), early and late mild cognitive impairment (n=279; n=372), and Alzheimer's dementia (n=216) subjects from ADNI-1/GO/2.

Measurements: Baseline amyloid status was based on first available CSF Aβ1-42 or, [11C]PiB or [18F]florbetapir (FBP) PET. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) and Functional Activities Questionnaire (FAQ) were co-analyzed using Growth Mixture Modeling (GMM) to define latent class trajectories for each amyloid group. Classification and Regression Tree (CART) analysis determined which variables best predicted trajectory class membership using a number of variables available to clinicians.

Results: GMMs found two trajectory classes (C1, C2) each for amyloid-positive (P; n=722) and negative (N; n=470) groups. Most (90%) in the negative group were C2N with mildly impaired baseline ADAS-Cog13, normal FAQ and nonprogression; 10% were C1N with moderately impaired baseline FAQ and ADAS-Cog13 and trajectory of moderately worsening scores on the FAQ. C1P (26%) had more impaired baseline FAQ and ADAS-Cog13 than C2P (74%) and a steeper declining trajectory. CART yielded 4 decision nodes (FAQ <10.5, FAQ <6.5, MMSE ≥26.5, age <75.5) in positive and 1 node (FAQ <6.5) in negative groups, with 91.4% and 92.8% accuracy for class assignments, respectively.

Conclusions: The trajectory pattern of greater decline in amyloid positive subjects was predicted by greater baseline impairment of cognition and function. While most amyloid-negative subjects had nonprogression irrespective of their diagnosis, a subgroup declined similarly to the gradually declining amyloid-positive group. CART predicted likely trajectory class, with known amyloid status, using variables accessible in a clinical setting, but needs replication.

Keywords: Alzheimer’s disease; Trajectory; beta-amyloid.

PubMed Disclaimer

Conflict of interest statement

Drs. Hochstetler, Wang, and Henley, and Mr. Case are full-time employees and minor shareholders of Eli Lilly and Company. Drs. Trzepacz and Yu and Ms. Degenhardt were full-time employees and minor shareholders of Eli Lilly and Company at the time this work was completed. Dr. Lyketsos has or is currently receiving grant support (research or CME) from NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Eli Lilly and Company, Ortho-McNeil, Bristol-Myers, Novartis, National Football League, Elan, Functional Neuromodulation; payment as a consultant or advisor from Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Eli Lilly and Company, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, Abbvie, Janssen, Orion, Otsuka, Servier, Astellas, and honorarium or travel support from Pfizer, Forest, Glaxo-Smith Kline, Health Monitor. Dr. Leoutsakos has received NIH funding and has been an unpaid consultant for Eli Lilly and Company.

LinkOut - more resources