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Clinical Manifestations
Ramit Ravona-Springer1,2,3, Shiraz Vered4, Abigail Livny3,5,6,7
1Geriatric psychiatry and memory unit, Sheba Medical Center, Ramat Gan, Israel.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
Summary
Reduced white matter integrity in specific brain areas is linked to more depressive symptoms in middle-aged individuals at high risk for Alzheimer's disease and related disorders (ADRD). This suggests white matter changes may be early neurodegeneration markers.
Area of Science:
- Neuroimaging
- Neurodegenerative Diseases
- Mental Health
Background:
- Reduced white-matter integrity may precede other brain imaging findings in individuals at risk for Alzheimer's disease and related disorders (ADRD).
- This integrity loss could be involved in the development and consequences of depression.
- Investigating this link in high-risk middle-aged individuals may reveal early neurodegeneration markers.
Purpose of the Study:
- To examine the relationship between white matter integrity and depressive symptoms.
- To identify potential early markers of neurodegeneration in individuals at high risk for ADRD.
Main Methods:
- Diffusion tensor imaging (DTI) assessed white matter integrity (fractional anisotropy and mean diffusivity).
- The Center for Epidemiological Studies-Depression (CESD) scale measured depressive symptoms.
- Linear and logistic regression models analyzed associations in 301 cognitively normal offspring of ADRD patients.
Main Results:
- Higher fractional anisotropy (FA) in the genu and cingulum was associated with lower CESD scores.
- Increased FA in these areas also correlated with decreased odds of clinical depression.
- No significant associations were found between other white matter tracts or mean diffusivity (MD) and depressive symptoms.
Conclusions:
- Disrupted white matter integrity in specific tracts is linked to depressive symptoms in midlife individuals at increased ADRD risk.
- These white matter alterations may serve as early biomarkers for neurodegeneration.
- Findings suggest potential for timely intervention and prevention strategies targeting white matter health.
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