# Impact of Diabetes on Cognitive and Perfusion Inefficiencies in Preclinical AD

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2021 · —

## Abstract

Diabetes affects more than 30 million Americans over the age of 18, including nearly one quarter of
Veterans. The estimated yearly cost of diabetes in the United States is $245 billion, and the medical
expenditures of people with diabetes is 2.3 times higher than they would be in the absence of diabetes. In
addition to the many medical complications and co-existing conditions associated with diabetes, diabetes also
confers a greater risk for developing Alzheimer’s disease (AD) and dementia. AD pathogenesis is thought to
begin many years prior to the clinical diagnosis, so there has been significant focus on the use of biological
methods to detect AD prior to the frank cognitive impairment that is observed in the mild cognitive impairment
(MCI) and dementia phases. While PET neuroimaging with radioactive tracers and lumbar puncture (LP) to
obtain cerebrospinal fluid levels of AD markers (Ab, p-tau, total tau) have drawn significant attention and are
important for our understanding of the pathogenesis of AD, these methods are not without limitations.
Specifically, these approaches are expensive, still in experimental phases in regard to understanding
implications of “positive” findings, invasive (require injection of radioactive tracers or LP), and often
inaccessible due to location (e.g., rural setting), cost, or medical contraindications (e.g., on blood thinners).
Therefore, there is a significant need to develop and implement sensitive neuropsychological markers that
capture subtle, preclinical cognitive changes, before objective impairment associated with MCI and dementia.
 The proposed study aims to examine neuropsychological (NP) process scores as a method for
detecting the earliest cognitive changes associated with diabetes and to use these scores to predict cognitive
and functional decline. NP process scores are derived from standard NP tests, but provide information about
how the Veteran obtained an overall total score (e.g., types of errors that were made, learning slope). Process
scores have been shown to add value in predicting future cognitive decline and can be used to identify subtle
cognitive decline in preclinical AD. This study will involve 1) a retrospective record review of 200 Veterans (100
with diabetes) without a neurocognitive disorder who previously completed a neuropsychological assessment
as part of their VA clinical care, 2) recruitment of a subset of these 200 Veterans (n=46; [23 with diabetes]) to
be followed longitudinally, and 3) prospective recruitment of 66 new Veterans (33 with diabetes) who will have
baseline arterial spin labeling magnetic resonance imaging to examine cerebral blood flow as a potential
marker of cognitive inefficiency in diabetes; they will also be followed longitudinally [(total longitudinal
n=112)]. This study is highly innovative in that it is the first to use NP process scores to identify subtle cognitive
changes and predict future decline in diabetic Veterans that do not yet have a neurocog...

## Key facts

- **NIH application ID:** 10041705
- **Project number:** 5IK2CX001865-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Kelsey R Thomas
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041705

## Citation

> US National Institutes of Health, RePORTER application 10041705, Impact of Diabetes on Cognitive and Perfusion Inefficiencies in Preclinical AD (5IK2CX001865-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10041705. Licensed CC0.

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