Neurological soft signs in neurodegenerative dementias: Results of the DemeNSS study

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Abstract Aim Neurological soft signs (NSSs) encompass subtle neurological abnormalities, often indicative of impaired motor and sensory integration, observed in various neuropsychiatric conditions. NSSs have been recently investigated as potential diagnostic markers in neurodegenerative dementias. We aimed to confirm an NSS increase in subjects with cognitive decline and evaluate them in the differential diagnosis of neurodegenerative dementias. Methods A sample of 93 subjects with dementia (34 with Alzheimer's disease [AD], 29 with frontotemporal dementia [FTD], 16 with Lewy body disease [LBD], and 14 with corticobasal syndrome [CBS]) and 93 healthy controls (HCs) were assessed using the 16‐item Heidelberg NSS Scale. Results Subjects with neurodegenerative dementias exhibited significantly higher NSS scores than HCs (20.4 ± 7.9 vs. 5.7 ± 4.2, p < 0.01). Notably, those with CBS/LBD showed markedly elevated NSSs compared to those with AD and FTD (26.2 ± 6.7 vs. 18.4 ± 7.1 and 16.6 ± 6.5, respectively, p < 0.01). Diagnosis, Mini‐Mental State Examination (MMSE), Frontal Assessment Battery, and anticholinergic burden were significant predictors of NSS expression in subjects with dementia. In HCs, only age and MMSE were significant predictors. A reduced Neurological Soft Signs (rNSS) Scale, including only five items that can be administered in less than a minute, demonstrated diagnostic performances comparable to the full NSS Scale. Conclusion NSSs are increased across neurodegenerative dementia subtypes, particularly in CBS and LBD. The Heidelberg NSS Scale, as well as its variant rNSS, may serve as quick and informative tools to be added to the visits in memory clinics.

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