TY - CHAP
T1 - Precision medicine approach to Alzheimer's disease
T2 - Successful pilot project
AU - Toups, Kat
AU - Hathaway, Ann
AU - Gordon, Deborah
AU - Chung, Henrianna
AU - Raji, Cyrus
AU - Boyd, Alan
AU - Hill, Benjamin D.
AU - Hausman-Cohen, Sharon
AU - Attarha, Mouna
AU - Chwa, Won Jong
AU - Jarrett, Michael
AU - Bredesen, Dale E.
N1 - Publisher Copyright:
© 2024 IOS Press. All rights reserved.
PY - 2024/2/22
Y1 - 2024/2/22
N2 - 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.
AB - 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.
KW - Clinical trial
KW - Mild cognitive impairment
KW - MRI volumetrics
KW - Neurodegeneration
KW - Systems medicine
UR - http://www.scopus.com/inward/record.url?scp=85189572914&partnerID=8YFLogxK
U2 - 10.3233/AIAD230086
DO - 10.3233/AIAD230086
M3 - Chapter
AN - SCOPUS:85189572914
SN - 9781643685007
SP - 256
EP - 267
BT - Handbook of Intervention and Alzheimer's Disease
PB - IOS Press
ER -