digoxin and Cognitive-Dysfunction

We examined cognitive function in older hospitalised patients with chronic atrial fibrillation (AF).. A prospective substudy of a multicentre randomised trial of an AF-specific disease management intervention (the Standard versus Atrial Fibrillation spEcific managemenT studY; SAFETY).. Three tertiary referral hospitals within Australia.. A total of 260 patients with chronic AF: mean age 72±11 years, 53% men, mean CHA2DS2-VASc score 4±2.. Cognitive function was assessed at baseline (during inpatient stay) using the Montreal Cognitive Assessment (MoCA).. The extent of mild cognitive impairment (MCI-defined as a MoCA score <26) in AF patients and identification of independent predictors of MCI.. Overall, 169 patients (65%, 95% CI 59% to 71%) were found to have MCI at baseline (mean MoCA score 21±3). Multiple deficits in cognitive domains were identified, most notably in executive functioning, visuospatial abilities and short-term memory. Predictors of MCI (age and sex-adjusted) were lower education level (technical/trade school level OR 6.00, 95% CI 2.07 to 17.42; <8 years school education OR 5.29, 95% CI 1.95 to 14.36 vs 8-13 years), higher CHA2DS2-VASc score (OR 1.46, 95% CI 1.23 to 1.74) and prescribed digoxin (OR 2.19, 95% CI 1.17 to 4.10).. MCI is highly prevalent amongst typically older high-risk patients hospitalised with AF. Routine assessment of cognitive function with adjustment of clinical management is indicated for this patient group.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Attention; Australia; Cardiotonic Agents; Chronic Disease; Cognition; Cognitive Dysfunction; Digoxin; Educational Status; Executive Function; Female; Humans; Linear Models; Male; Memory, Short-Term; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Odds Ratio; Orientation; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Tertiary Care Centers

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.

Topics: Animals; Brain Ischemia; Carotid Stenosis; Cognitive Dysfunction; Digoxin; Disease Models, Animal; Mice; Mice, Inbred C57BL; White Matter