Brain perivascular diffusion and cognitive impairment in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic cardiovascular disorder that may involve extra-cardiac organs, including the brain. This study aimed to investigate whether brain perivascular diffusivity, assessed using diffusion tensor image analysis along the perivascular space (DTI-ALPS), is associated with cognitive performance, assessed with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), in patients with HFpEF.

Thirty-five patients with HFpEF and 20 healthy controls underwent brain diffusion kurtosis imaging and neuropsychological assessment. Left, right, and mean DTI-ALPS indices were calculated for each participant. Group differences were evaluated using independent-samples t tests, Mann-Whitney U tests, or chi-square tests as appropriate. Associations between DTI-ALPS indices and cognitive outcomes were examined using Spearman correlation analyses and multivariable linear regression models adjusted for age, sex, and educational level.

Compared with healthy controls, patients with HFpEF had lower MoCA (22.34 ± 3.38 vs. 28.70 ± 1.69; t = 9.29, p < 0.01) and MMSE scores (median 24.00 vs. 28.50; Z = -5.03, p < 0.01), together with poorer visuospatial/executive function, attention, language, abstraction, and delayed recall (all p < 0.01), whereas naming and orientation did not differ between groups (both p > 0.05). The left DTI-ALPS index was lower in patients than in controls (1.64 ± 0.24 vs. 1.77 ± 0.21, t = 2.08, p = 0.04), whereas the right and mean indices showed no significant group difference (p = 0.54 and p = 0.16, respectively). After adjustment for age, sex, and educational level, a lower left DTI-ALPS index was independently associated with worse MMSE (β = 0.031, p = 0.001), MoCA (β = 0.021, p = 0.007), and delayed recall scores (β = 0.050, p = 0.009).

HFpEF was associated with cognitive impairment and a left-predominant reduction in perivascular diffusivity as reflected by DTI-ALPS. These findings suggest that DTI-ALPS may be a candidate neuroimaging marker of brain involvement in HFpEF. Given the cross-sectional design, causal and predictive interpretations should be avoided until confirmed by longitudinal multimodal studies.