# Long-Term Nicotine Treatment of Mild Cognitive Impairment - Bridge Funding

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $784,085

## Abstract

Precursor conditions to Alzheimer's disease (AD) such as Mild Cognitive Impairment (MCI) are now a target of
patient identification and potential treatment, as studies clearly showing that the risk of progression to dementia
is very high. Despite attempts to develop new treatments for AD and its precursor, MCI, methods of interrupting
the course of illness and preventing progression have proven elusive. Treatment strategies for AD based on
molecular pathologies (such as Aβ) have thus far produced equivocal or negative results. Investigation is thus
shifting to the potential treatment of precursor conditions, including MCI, pre-MCI, and subjects at risk with
identification via genetics or other biomarkers.
 Losses of cholinergic neurons and particularly nicotinic cholinergic receptors have been shown to be
principally related to cognitive decline in AD. However, approved treatments for AD have not significantly
improved MCI, despite clear evidence of alteration of cholinergic function at this stage, Thus nonspecific
enhancement of cholinergic function does not appear to be a fruitful strategy for either enhancing long-term
cognitive functioning in MCI, nor retarding the progression to AD.
 There is a continuing search for new treatments that will improve cognitive symptoms while potentially be
disease modifying. Nicotine may be one of those molecules and is easily available, inexpensive, and easy to
use. We have performed a double-blind 6 month pilot trial showing that nicotine treatment significantly
improved cognitive performance in the areas of attention and episodic memory, showed improving global
ratings of functioning and self-rated memory problems, and was well tolerated with an impressive safety profile
and no abuse liability (Newhouse, P., K. Kellar, et al. (2012). Neurology 78(2): 91-101). We now propose a
definitive 2-year multi-center clinical trial to test whether daily transdermal nicotine will produce sustained
cognitive, clinical, and functional benefits in patients with MCI. We also plan to test whether nicotine will
change the underlying biology related to developing AD by monitoring biological markers including structural
and functional brain imaging and measures of AD pathology in spinal fluid. Our primary hypothesis is that
transdermal nicotine will enhance cognitive performance and symptoms of cognitive dysfunction compared to
placebo and that this difference will be sustained over two years.
 This proposed study has broad clinical and scientific significance. If the hypotheses were validated,
these findings would support a novel, broadly available, and inexpensive intervention for MCI and would
encourage early treatment intervention to improve symptoms and/or retard progression of cognitive
impairment. This would be the longest trial of nicotine or nicotinic agonists to date and if successful would lead
to combined trials with other symptomatic agents and/or agents that might directly interact with Aβ or tau-
related mechani...

## Key facts

- **NIH application ID:** 10209485
- **Project number:** 3R01AG047992-06S1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Paul S. Aisen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $784,085
- **Award type:** 3
- **Project period:** 2015-09-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209485

## Citation

> US National Institutes of Health, RePORTER application 10209485, Long-Term Nicotine Treatment of Mild Cognitive Impairment - Bridge Funding (3R01AG047992-06S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10209485. Licensed CC0.

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