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;40(6):e70107.
doi: 10.1002/gps.70107.

Neuropsychiatric Symptoms and White Matter Hyperintensities in Older Cognitively Unimpaired Men Versus Women

Ioannis Liampas  1 , Daniil Tsirelis  1 , Silvia Demiri  2 , Vasileios Siokas  1 , Antonia Tsika  1 , Elli Zoupa  3 , Polyxeni Stamati  1 , Lambros Messinis  4 , Grigorios Nasios  5 , Efthimios Dardiotis  1   3
Affiliations

Neuropsychiatric Symptoms and White Matter Hyperintensities in Older Cognitively Unimpaired Men Versus Women

Ioannis Liampas et al. Int J Geriatr Psychiatry. 2025 Jun.

Abstract

Objectives: We aimed to examine association patterns of white matter hyperintensities (WMH) with neuropsychiatric symptoms (NPS) in men versus women.

Methods: We performed a cross-sectional analysis of data acquired from the National Alzheimer's Coordinating Center database. Cognitively unimpaired participants aged ≥ 50 years with data on WMH severity were studied. Using Cardiovascular Health Study scores, WMH were coded as no to mild (score: 0-4), moderate (score: 5-6) or extensive (score: 7-8). NPS were quantified on the Neuropsychiatric Inventory Questionnaire. For the purposes of the main analysis, participants were dichotomized for presence of each NPS (0: absent; 1: present). Adjusted binary logistic regression models estimated the odds of having each of 12 NPS by sex-WMH status. To confirm the validity of our findings, the correlations between NPS severity and WMH burden were also separately explored in men and women.

Results: Among 4617 participants with normal cognition, there were 1502 men and 2685 women with no to mild WMH changes, 102 men and 274 women with moderate WMH changes and 19 men and 35 women with extensive WMH changes. Greater WMH burden (especially extensive changes) was related to increased odds of lability symptoms (agitation, disinhibition, irritability) and apathy in men but not women. Elation and appetite disorders followed the same trend but failed to achieve statistical significance. The exploratory analysis revealed positive correlations between these symptoms' severity with WMH burden in men but not in women.

Conclusions: WMH burden was differentially associated with NPS in older men versus women with normal cognition.

Keywords: agitation; apathy; appetite disorders; disinhibition; elation; irritability.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Prevalence of neuropsychiatric manifestations per sex by white matter hyperintensities group.
FIGURE 2
FIGURE 2
Linear relationship between white matter hyperintensities' burden and neuropsychiatric symptoms' severity in men (blue coloring) women (orange coloring).
See this image and copyright information in PMC

References

    1. Wardlaw J. M., Valdés Hernández M. C., and Muñoz‐Maniega S., “What Are White Matter Hyperintensities Made of?: Relevance to Vascular Cognitive Impairment,” JAHA 4, no. 6 (June 2015): e001140, 10.1161/jaha.114.001140. - DOI - PMC - PubMed
    1. Lin J., Wang D., Lan L., and Fan Y., “Multiple Factors Involved in the Pathogenesis of White Matter Lesions,” BioMed Research International 2017 (2017): 1–9, 10.1155/2017/9372050. - DOI - PMC - PubMed
    1. Freeze W. M., Jacobs H. I. L., De Jong J. J., et al., “White Matter Hyperintensities Mediate the Association Between Blood‐Brain Barrier Leakage and Information Processing Speed,” Neurobiology of Aging 85 (January 2020): 113–122, 10.1016/j.neurobiolaging.2019.09.017. - DOI - PubMed
    1. Ryu W. S., Woo S. H., Schellingerhout D., et al., “Grading and Interpretation of White Matter Hyperintensities Using Statistical Maps,” Stroke 45, no. 12 (December 2014): 3567–3575, 10.1161/strokeaha.114.006662. - DOI - PubMed
    1. Zhuang F. J., Chen Y., He W. B., and Cai Z. Y., “Prevalence of White Matter Hyperintensities Increases With Age,” Neural Regen Res 13, no. 12 (2018): 2141, 10.4103/1673-5374.241465. - DOI - PMC - PubMed

LinkOut - more resources