Clinical Manifestations

Area of Science:

• Neurology
• Neuropsychiatry
• Gerontology

Background:

• Apathy and depression frequently co-occur in neurocognitive disorders (NCDs).
• White matter hyperintensities (WMH), markers of microvascular damage, are individually linked to apathy and depression.
• Limited understanding exists regarding the spatial distribution and sex-specific patterns of these co-occurring symptoms and their relation to WMH.

Purpose of the Study:

• To investigate the association between comorbid apathy and depression (A+D) and white matter hyperintensities (WMH) severity in individuals with NCDs.
• To explore potential sex-specific differences in the relationship between apathy, depression, and WMH.

Main Methods:

• Longitudinal data from the COMPASS-ND cohort of 803 participants with various NCDs were analyzed.
• Participants were categorized into four groups: apathy only (AO), depressive symptoms only (DO), A+D, and neither apathy nor depression (NAD).
• WMH severity was assessed using the Fazekas scale in periventricular (PV) and subcortical (SC) regions; ordinal regression analyses examined group differences, with separate analyses for sex-specific patterns.

Main Results:

• Comorbid apathy and depression (A+D) were significantly associated with higher periventricular WMH (PVWMH) severity (β=0.508, p=0.01), but not subcortical WMH (SCWMH).
• Neither apathy only (AO) nor depressive symptoms only (DO) were associated with PVWMH or SCWMH.
• In sex-specific analyses, males with A+D showed significantly higher PVWMH severity (β=0.765, p=0.002), while no significant associations were found in females.

Conclusions:

• The study found a positive association between comorbid apathy and depression (A+D) and periventricular white matter hyperintensities (PVWMH), particularly in males.
• No significant associations were observed between WMH severity and isolated apathy or depressive symptoms, nor in females with comorbid symptoms.
• Findings highlight the importance of regional and sex-specific analyses in understanding the relationship between WMH and comorbid apathy/depression in NCDs for potential treatment implications.