Abstract Body: Introduction: Stroke is a well-established independent risk factor for the development of dementia. Most dementia patients exhibit mixed brain pathologies, with histological evidence of ischemia and Aβ plaque accumulation, observed at autopsy. It is known that apnea/breathing disorders are independent risk factors for cognitive dysfunction and the progression of dementia. Our previous work suggested stroke impairs breathing control in wildtype mice. Here we hypothesize that, in mice with pre-existing dementia, stroke will exacerbate their respiratory dysfunction and further impair cognitive function.
Methods: We used Tg-SwDI mice as a model for cerebral amyloid angiopathy (CAA), a major type of dementia. Female (11 to 13 months old) Tg-SwDI mice underwent pd-MCAO (permanent distal middle cerebral artery occlusion surgery) with age and sex matched wildtype and sham controls. Barnes Maze and Novel Object Recognize Test (NORT) were used for cognitive assessment, while whole-body plethysmography captured respiratory metrics, including apnea rate at 6 weeks post-surgery. All data are presented as Mean±SEM.
Results: Tg-SwDI mice without stroke showed significant increases in apnea rates (per min) compared to the wide-type mice without stroke (5.8±0.26 vs. 1.04±0.11, p=0.0003, n=7 and 5) and displayed worsen performance in Barnes Maze (escape latency 59.5±11.6 vs. 23.7±6.1, p=0.044, n=7 and 5) and NORT (percentage time spent with novel object 42.0±5.8% vs. 61.9±6.2%, p=0.019, n=7 and 5). pd-MCAO increased apnea events in Tg-SwDI group (9.5±0.91 vs. 5.8±0.26, p=0.0009, n=9 and 7) vs. Tg-SwDI mice without stroke. Tg-SwDI mice with pd-MCAO exhibited worsen performance in Barnes Maze escape latencies (93.7±10.4 vs. 59.5±11.6, p=0.027, n=9 and 7) compared with Tg-SwDI mice without stroke. There was also a non-significant reduced novel object interaction time in NORT (36.8%±3.54 vs. 42.0%±5.8, p=0.43, n=9 and 7).
Conclusions: Stroke worsens both respiratory dysfunction and cognitive memory impairment in CAA mice. The increased breathing disorder may be a contributing factor for worsened cognition in CAA mice.