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<p>Substantia nigra hyperechogenicity (SN+) detected by transcranial sonography (TCS) has been proposed as a risk marker for synucleinopathies, particularly Parkinson’s disease. Its role in prodromal dementia with Lewy bodies (DLB) remains insufficiently explored. To examine clinical, cognitive, genetic, EEG, and plasma biomarker differences between SN+ and normal echogenicity (SN−) individuals in a well-characterized at-risk-of-DLB cohort, with additional sex-stratified analyses. A total of 121 participants aged 55–70 years from an at-risk-of-DLB cohort underwent TCS, neurological and neuropsychological assessment, nighttime wrist actigraphy, high-density EEG, genetic testing for APOE allelic variants, and plasma biomarker analysis (NfL, GFAP, pTau181). SN status was defined using laboratory-specific cut-offs. Group differences were assessed using non-parametric statistics with relevant corrections for multiple comparisons and adjustment for age. SN+ status as compared to SN− status was associated with poorer verbal memory performance and altered visuo-constructive performance (driven mostly by males), and significant differences in distinct actigraphy-derived sleep parameters. SN+ participants showed higher plasma NfL levels (particularly in males) and a higher prevalence of DLB-specific EEG patterns (driven by females). No significant associations were observed for global cognition, motor parkinsonism, cognitive fluctuations, hallucinations, REM sleep behavior disorder, depressive symptoms, olfactory function, plasma biomarkers of degeneration, neuroinflammation, β-amyloid deposition, or APOE status. In individuals at risk of DLB, SN hyperechogenicity is linked to early markers of neurodegeneration and cholinergic dysfunction, including elevated NfL and DLB-specific EEG abnormalities, as well as selective posterior cortical cognitive impairment and sleep disturbances. The observed sex-specific effects require further investigation.</p>

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The correlates of hyperechogenicity of the substantia nigra in subjects at risk of dementia with Lewy bodies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月14日

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  • Kateřina Zelníčková,
  • David Ondráček,
  • Marek Mikulec,
  • Jiří Mekyska,
  • Jan Farkaš,
  • Martin Lamoš,
  • Irena Rektorová

摘要

Substantia nigra hyperechogenicity (SN+) detected by transcranial sonography (TCS) has been proposed as a risk marker for synucleinopathies, particularly Parkinson’s disease. Its role in prodromal dementia with Lewy bodies (DLB) remains insufficiently explored. To examine clinical, cognitive, genetic, EEG, and plasma biomarker differences between SN+ and normal echogenicity (SN−) individuals in a well-characterized at-risk-of-DLB cohort, with additional sex-stratified analyses. A total of 121 participants aged 55–70 years from an at-risk-of-DLB cohort underwent TCS, neurological and neuropsychological assessment, nighttime wrist actigraphy, high-density EEG, genetic testing for APOE allelic variants, and plasma biomarker analysis (NfL, GFAP, pTau181). SN status was defined using laboratory-specific cut-offs. Group differences were assessed using non-parametric statistics with relevant corrections for multiple comparisons and adjustment for age. SN+ status as compared to SN− status was associated with poorer verbal memory performance and altered visuo-constructive performance (driven mostly by males), and significant differences in distinct actigraphy-derived sleep parameters. SN+ participants showed higher plasma NfL levels (particularly in males) and a higher prevalence of DLB-specific EEG patterns (driven by females). No significant associations were observed for global cognition, motor parkinsonism, cognitive fluctuations, hallucinations, REM sleep behavior disorder, depressive symptoms, olfactory function, plasma biomarkers of degeneration, neuroinflammation, β-amyloid deposition, or APOE status. In individuals at risk of DLB, SN hyperechogenicity is linked to early markers of neurodegeneration and cholinergic dysfunction, including elevated NfL and DLB-specific EEG abnormalities, as well as selective posterior cortical cognitive impairment and sleep disturbances. The observed sex-specific effects require further investigation.