Executive functioning and processing speed as predictors of global cognitive decline in Alzheimer's disease

John P Haran; A M Barrett; YuShuan Lai; Samuel N Odjidja; Protiva Dutta; Patrick M McGrath; Imane Samari; Lethycia Romeiro; Abigail Lopes; Vanni Bucci; Beth A McCormick

doi:10.1177/25424823251363549

Executive functioning and processing speed as predictors of global cognitive decline in Alzheimer's disease

J Alzheimers Dis Rep. 2025 Aug 6:9:25424823251363549. doi: 10.1177/25424823251363549. eCollection 2025 Jan-Dec.

Authors

John P Haran^{1

2

3}, A M Barrett⁴, YuShuan Lai^{2

3}, Samuel N Odjidja¹, Protiva Dutta¹, Patrick M McGrath¹, Imane Samari¹, Lethycia Romeiro¹, Abigail Lopes¹, Vanni Bucci^{2

3}, Beth A McCormick^{2

3}

Affiliations

¹ Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
² Department of Microbiology, University of Massachusetts Medical School, Worcester, MA, USA.
³ Program in Microbiome Research, University of Massachusetts Medical School, Worcester, MA, USA.
⁴ Department of Neurology, UMass Chan Medical School and UMass Memorial Healthcare, Worcester, MA, USA.

Abstract

Background: Better cognitive tools to predict disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD) are needed.

Objective: In this prospective longitudinal cohort, we are testing if changes in the cognitive domains of executive functioning and processing speed can predict global cognitive decline.

Methods: We assessed patients with MCI, AD, and cognitively healthy controls (cHC) using NIH toolbox assessments for processing speed and executive functioning and overall cognitive decline by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog).

Results: Among 184 participants over a median follow-up of 540 days, both between- and within-subjects variance in NIH toolbox and ADAS-Cog assessments increased from cHC to MCI to AD patients. Among patients with AD (n = 24), pattern comparison processing speed (PCPS) and dimensional change card sort tests (DCCS) declined at 3 and 6 months prior to global cognitive decline (p = 0.008 and 0.0012). A 5-point decrease in either PCPS or DCCS increased risk of global cognitive decline (HR 1.32 (1.08-1.60) and 1.62 (1.16-2.26)).

Conclusions: Testing for cognitive domains of processing speed and executive functioning may predict subsequent global cognitive.

Keywords: Alzheimer's disease; Alzheimer's disease assessment scale-cognitive; NIH toolbox; cognitive testing; mild cognitive impairment.

Grants and funding

R01 AG067483/AG/NIA NIH HHS/United States