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Observational Study
. 2024 Jun 6:13:e56726.
doi: 10.2196/56726.

Linking Dementia Pathology and Alteration in Brain Activation to Complex Daily Functional Decline During the Preclinical Dementia Stages: Protocol for a Prospective Observational Cohort Study

Pierfilippo De Sanctis  1   2 , Jeannette R Mahoney  1 , Johanna Wagner  3 , Helena M Blumen  1   4 , Wenzhu Mowrey  5 , Emmeline Ayers  1 , Claudia Schneider  1 , Natasha Orellana  1 , Sophie Molholm  2 , Joe Verghese  1   4
Affiliations
Observational Study

Linking Dementia Pathology and Alteration in Brain Activation to Complex Daily Functional Decline During the Preclinical Dementia Stages: Protocol for a Prospective Observational Cohort Study

Pierfilippo De Sanctis et al. JMIR Res Protoc. .

Erratum in

Abstract

Background: Progressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing).

Objective: Our goal is to establish the neural signature of decline in CdF during the preclinical dementia period.

Methods: Gait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF.

Results: We provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-β) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF.

Conclusions: By establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits.

International registered report identifier (irrid): DERR1-10.2196/56726.

Keywords: EEG; electroencephalographic; mobility; preclinical dementia stages.

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Conflict of interest statement

Conflicts of Interest: JRM has a financial interest in JET Worldwide Enterprises Inc, a digital health startup spun out of research conducted at the Albert Einstein College of Medicine that is not related to this project. All other authors report no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this paper apart from those disclosed.

Figures

Figure 1
Figure 1
Sequence of events leading to decline in CdF. CdF: complex daily function; Cog.: cognitive; MCI: mild cognitive impairment; Unimp.: unimpaired.
Figure 2
Figure 2
Recruitment and procedures conducted under this proposal. Aβ: amyloid beta; CdF: complex daily function; CU: cognitively unimpaired; fun.: function; max.: maximum; MoCA: Montreal Cognitive Assessment; MRI: magnetic resonance imaging; T: phosphorylated τ; WMH: white matter hyperintensities.
Figure 3
Figure 3
Participant during the visually perturbed walking task.
Figure 4
Figure 4
The neural signature of limitations in CdF and unique gait-related electroencephalographic activation. CdF: complex daily function; med.: medial; pert.: perturbed; PP: posterior parietal; SM: sensorimotor; unpert.: unperturbed; V.: visually.
Figure 5
Figure 5
Analysis pipeline for separating brain activity from non–brain related artifacts during MoBI recording. ERSP: event-related spectral perturbation; IC: independent components; ICA: independent component analysis; LH: left heel strike; LTO: left toe off; MoBI: mobile brain body imaging; RH: right heel strike; RTO: right toe off.
Figure 6
Figure 6
Individuals with unique grEEG pattern have smaller cuneus, lingual, ant. cingulate, and increased white matter burden of the fimbra, which connects the hippocampus. Act.: activity; ant.: anterior; Anteri.: anterior; grEEG: gait-related electroencephalographic; MRI: magnetic resonance imaging; WMH: white matter hyperintensities.
Figure 7
Figure 7
Less exercise is related to less β desynchronization during DTW. DTW: dual-task walking; W: walking.
See this image and copyright information in PMC

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