Post-Stroke Cognitive Impairment and Dementia

Abstract

Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbid neurodegenerative pathology, which is common in elderly individuals and can contribute to the clinical expression of PSCID. Manifestations of cerebral small vessel disease, such as covert brain infarcts, white matter lesions, microbleeds, and cortical microinfarcts, are also common in patients with stroke and likewise contribute to cognitive outcomes. Although studies of PSCID historically varied in the approach to timing and methods of diagnosis, most of them demonstrate that older age, lower educational status, socioeconomic disparities, premorbid cognitive or functional decline, life-course exposure to vascular risk factors, and a history of prior stroke increase risk of PSCID. Stroke characteristics, in particular stroke severity, lesion volume, lesion location, multiplicity and recurrence, also influence PSCID risk. Understanding the complex interaction between an acute stroke event and preexisting brain pathology remains a priority and will be critical for developing strategies for personalized prediction, prevention, targeted interventions, and rehabilitation. Current challenges in the field relate to a lack of harmonization of definition and classification of PSCID, timing of diagnosis, approaches to neurocognitive assessment, and duration of follow-up after stroke. However, evolving knowledge on pathophysiology, neuroimaging, and biomarkers offers potential for clinical applications and may inform clinical trials. Preventing stroke and PSCID remains a cornerstone of any strategy to achieve optimal brain health. We summarize recent developments in the field and discuss future directions closing with a call for action to systematically include cognitive outcome assessment into any clinical studies of poststroke outcome.

Alzheimer’s Disease Connected Genes in the Post-Ischemic Hippocampus and Temporal Cortex

“…Both disease entities, i.e. AD and BI, are characterized by cerebral amyloid angiopathy [ 30 ]. Second, brain ischemia and AD have shared risk factors such as: hyperlipidemia, hypertension, obesity and diabetes [ 31 , 32 ].…”

“…BI is the second naturally happening pathology after AD, which triggers predominantly the death of pyramidal neuronal cells in the CA1 area of the hippocampus [ 2 , 4 ]. Post-ischemic hippocampus is considered to be the main neuronal area underlying the impairment of episodic memory, which is the earliest and most visible clinical symptom before dementia following ischemia with AD phenotype [ 3 , 30 , 41 , 42 , 43 , 44 , 45 ]. Also, ischemia is responsible for serious damage to the temporal cortex [ 37 ], which is the target region of the main axonal output network from the hippocampus.…”

“…Also, ischemia is responsible for serious damage to the temporal cortex [ 37 ], which is the target region of the main axonal output network from the hippocampus. These areas are structurally and functionally connected to each other and are important for learning and memory phenomena [ 3 , 30 , 41 , 42 , 43 , 44 , 45 ]. The connotation of increased risk of dementia following ischemic brain injury with age, atrophy of the hippocampus and neurodegenerative damages in the temporal cortex with hemorrhages has been observed [ 2 , 30 , 37 , 46 , 47 , 48 ].…”

Ischemic Brain Neurodegeneration

“…Stroke is divided into two categories: ischemic and hemorrhagic. Ischemic stroke accounts for approximately 70–85% of all cases [ 5 , 6 ]. Clinically, stroke is defined as local damage to the parenchyma of the brain caused by a lack of blood supply by occlusion or narrowing of an artery to a specific region, resulting in the death of neurons [ 5 ].…”

“…Third, the neuroinflammatory response plays an important role in the progression of post-ischemic neurodegeneration of the brain as well as in Alzheimer’s disease [ 14 ]. Fourth, data suggest that post-ischemic brain neurodegeneration induces the neuropathology of Alzheimer’s disease-specific folding proteins, such as amyloid and tau protein, leading to the development of plaques, neurofibrillary tangles and cerebral amyloid angiopathy [ 6 , 13 ]. Fifth, dysfunction of the autophagy, mitophagy, and apoptosis ( Table 2 ) genes is involved in post-ischemic neurodegeneration as in Alzheimer’s disease [ 7 , 13 ].…”