Affiliations: [a] Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy
| [b] Department of Experimental Medicine and Surgery, University of Roma Tor Vergata, Rome, Italy
| [c] IRCCS Fondazione Santa Lucia, Rome, Italy
Correspondence:
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Correspondence to: Tommaso Schirinzi, MD, Neurology Unit, Department of Systems Medicine, University of Roma Tor Vergata, via Montpellier 1, 00133, Rome, Italy. Tel.: +0039 06 72596010; Fax: +0039 06 72596006; E-mail: t.schirinzi@yahoo.com.
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 (Aβ42), 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 Aβ42 levels but not with t-tau and p-tau. AD patients also presented SAI impairment directly related to UPDRS part 3 score and Aβ42 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 Aβ42 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.
