Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 25;4(2):e70143.
doi: 10.1002/pcn5.70143. eCollection 2025 Jun.

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

Federico Emanuele Pozzi  1   2   3 , Anna Falco  3 , Gaia Gotti  3 , Giuseppe Fiamingo  3 , Giulia Remoli  1   2   3 , Ildebrando Appollonio  1   2   3 , Carlo Ferrarese  1   2   3 , Lucio Tremolizzo  1   2   3
Affiliations

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

Federico Emanuele Pozzi et al. PCN Rep. .

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.

Keywords: Alzheimer' disease; clinical neurology; cognition; dementia; neurodegeneration.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
NSS expression across diagnostic categories with the full Heidelberg Neurological Soft Sign (NSS) Scale. AD, Alzheimer's disease; CBS, corticobasal syndrome; FTD, frontotemporal dementia; LBD, Lewy body disease.
Figure 2
Figure 2
Receiver operating characteristic (ROC) curves for neurological soft signs (NSSs) performances in differentiating (a) patients from healthy controls and (b) patients with corticobasal syndrome (CBS)/Lewy body disease (LBD) from those with Alzheimer's disease (AD)/frontotemporal dementia (FTD) on the full Heidelberg NSS Scale.
Figure 3
Figure 3
Receiver operating characteristic (ROC) curves for neurological soft signs (NSSs) performances in differentiating (a) patients from healthy controls and (b) patients with corticobasal syndrome (CBS)/Lewy body disease (LBD) from those with Alzheimer's disease (AD)/frontotemporal dementia (FTD) on the reduced Neurological Soft Signs (rNSS) Scale.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Zhao Q, Li Z, Huang J, Yan C, Dazzan P, Pantelis C, et al. Neurological soft signs are not “soft” in brain structure and functional networks: evidence from ALE meta‐analysis. Schizophr Bull. 2014;40(3):626–641. - PMC - PubMed
    1. Dimitri‐Valente G, Rigucci S, Manfredi G, Girardi P, Ferracuti S. [Neurological soft signs: meaning and relevance along the course of psychiatric illness. An objective and rapid screening for psychosis?]. Rivista di psichiatria. 2012;47(6):465–478. - PubMed
    1. Tucker G, Campion E, Silberfarb P. Sensorimotor functions and cognitive disturbance in psychiatric patients. Am J Psychiatry. 1975;Jan 132(1):17–21. - PubMed
    1. Mechri A, Gassab L, Slama H, Gaha L, Saoud M, Krebs MO. Neurological soft signs and schizotypal dimensions in unaffected siblings of patients with schizophrenia. Psychiatry Res. 2010;175(1–2):22–26. - PubMed
    1. Tapancı Z, Yıldırım A, Boysan M. Neurological soft signs, dissociation and alexithymia in patients with obsessive‐compulsive disorder (OCD) and healthy subjects. Psychiatry Res. 2018;Feb 260:90–97. - PubMed

LinkOut - more resources