[R01] Circuit-based multi-focal neurostimulation to target depression and memory in older adults with Alzheimer's dementia
Ente: National Institute on Aging
Scadenza: 2031-07-31
Importo max: 889.728 EUR
Paese: US
Descrizione
Project Summary: In older adults with mild dementia due to Alzheimer’s disease (AD), difficulties with
instrumental activities of daily living stem not only from memory loss, but also from co-occurring depressive
symptoms (DEP). DEP + AD is highly prevalent and major driver of disability in older adults, yet most patients
with this combination of symptoms do not derive meaningful benefit from current treatments. There is a
pressing need to develop safe, multi-component interventions designed to maximize functional capacity in this
vulnerable population by simultaneously targeting memory and DEP. It is now well established that depressive
and memory symptoms arise from altered function within specific brain circuits, and, that different types of
transcranial electrical stimulation (tES) can target these brain circuits to provide symptomatic relief to this
population. Parallel lines of preliminary evidence specifically suggest that transcranial direct current stimulation
targeting left prefrontal cortex (tDCSPFC) can improve depressive symptoms in people with major depressive
disorder, whereas transcranial alternating current stimulation targeting the left angular gyrus (tACSAG) at
gamma frequency (40Hz) can improve episodic memory in people with moderate dementia. At the same time,
technological advances now allow researchers to: (1) study and optimize multi-channel stimulation montages
(i.e., electrode placement and current parameters) using individualized electric field (E-field) modeling; (2)
target multiple brain networks simultaneously within a single montage; (3) implement active-sham protocols
that enhance double-blinding and control for potential peripheral stimulation effects; and (4) deliver stimulation
at home utilizing a remotely monitored caregiver-led administration that has been found to be safe and
effective, while increasing treatment access, relieving patients of travel burden, and limiting geographical
selection bias. Building upon these preliminary studies and advances, we propose to conduct a phase II,
randomized, sham-controlled, double-blinded, parallel-arm trial. The first aim of this study is to assess the
separate and combined effects of tACSAG at gamma frequency and tDCSPFC on memory, depressive
symptoms, and instrumental activities of daily living in DEP + AD. The second aim is to determine how much of
the clinical effects on memory on the one hand, and DEP on the other hand, depend upon the amount of the E-
field induced respectively in the left angular gyrus and the left dorsolateral prefrontal cortex, as assessed by
individualized E-field high-resolution modelling. The third aim will assess intervention-related changes in brain
activity using resting-state EEG. This project aims to demonstrate that tACS and tDCS can be effectively
integrated into a single, scalable home-based intervention to maximize functional gains in older adults with mild
dementia due to AD + DEP. It will also provide insights into the specificit
Istituzione: TUFTS MEDICAL CENTER
PI: Davide Cappon
Progetto: 1R01AG099908-01
Settori: National Institute on Aging
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