Amyloid-Mediated Cholinergic Dysfunction in Motor Impairment Related to Alzheimer's Disease

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Abstract

Background: Although motor disturbances parallel the course of dementia, worsening both quality of life and social costs, the pathogenesis remains still unclear. Objective: Through the combination of cerebrospinal fluid (CSF) biomarkers assessment and transcranial magnetic stimulation (TMS) protocols, here we provided a cross-sectional study to understand pathogenic mechanisms of Alzheimer's disease (AD)-related early motor disturbances. Methods: The motor phenotype, as defined with Unified Parkinson's Disease Rating Scale (UPDRS) part 2-3, Rating Scale for Gait Evaluation in Cognitive Deterioration (RSEGCD) and Tinetti scale, together with CSF profile of amyloid-β 42 (Aβ 42), total-tau, and phosphorylated-tau were determined in 37 AD patients and compared to 18 patients with vascular dementia (VaD). A TMS protocol of short afferent inhibition (SAI) was further applied on a subset of AD patients. Clinical, biochemical, and neurophysiological data were then compared and correlated in order to find significant associations. Results: AD patients exhibited subtle locomotor impairment and slight extrapyramidal signs. Main motor features (UPDRS part 3, RSGECD, and Tinetti scale scores) correlate with Aβ 42 levels but not with t-tau and p-tau. AD patients also presented SAI impairment directly related to UPDRS part 3 score and Aβ 42 levels. Motor disturbances of VaD group did not differ statistically from AD and did not correlate with CSF biomarkers. Conclusions: The association of motor disturbances with low Aβ 42 CSF levels and individual SAI suggests that amyloid-mediated degeneration of cholinergic system may account for early AD-related motor impairment, providing interesting insights either for frailty stratification of patients or personalized therapies.

Original languageEnglish
Pages (from-to)525-532
Number of pages8
JournalJournal of Alzheimer's Disease
Volume64
Issue number2
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • Alzheimer's disease
  • amyloid
  • cholinergic
  • frailty
  • gait
  • locomotor
  • vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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