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Randomized Controlled Trial
. 2022;88(4):1411-1421.
doi: 10.3233/JAD-215707.

Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project

Kat Toups  1 , Ann Hathaway  2 , Deborah Gordon  3 , Henrianna Chung  4 , Cyrus Raji  5 , Alan Boyd  6 , Benjamin D Hill  7 , Sharon Hausman-Cohen  8 , Mouna Attarha  9 , Won Jong Chwa  10 , Michael Jarrett  4 , Dale E Bredesen  11
Affiliations
Randomized Controlled Trial

Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project

Kat Toups et al. J Alzheimers Dis. 2022.

Abstract

Background: Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy.

Objective: To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial.

Methods: Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months.

Results: All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved.

Conclusion: Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.

Keywords: Clinical trial; MRI volumetrics; mild cognitive impairment; neurodegeneration; systems medicine.

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Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/21-5707r2).

Figures

Fig. 1
Fig. 1
Neurocognitive index for all 25 patients at baseline, 3 months, 6 months, and 9 months of treatment.
Fig. 2
Fig. 2
Neurocognitive indices (NCI) for the 25 patients at baseline, 3 months, 6 months, and 9 months. Dots represent scores, boxes represent second and third quartiles, horizontal lines within boxes represent medians, x represents means, and whiskers represent first and fourth quartiles. The ordinate represents NCI as percentile for age.
Fig. 3
Fig. 3
MoCA scores (dots), means (x), medians (bars; note that the median at 6 months was 29), and lowest and highest quartiles (whiskers) for the 25 subjects.
See this image and copyright information in PMC

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