Post-stroke dementia (PSD) refers to all types of dementia that occur after stroke, including vascular dementia (VaD), Alzheimer’s disease (AD) or other degenerative dementias, and mixed dementias. Epidemiological investigations have shown that stroke increases the risk of dementia by at least 2-fold; the incidence of dementia within 1 year of stroke onset ranges from 7.4% to 41.3%, depending on the study population and study methods. Long-term follow-up studies have shown that PSD affects at least half of stroke survivors, increases stroke mortality and disability rates, and severely affects survival time. I. Prevention of PSD The pathogenesis of PSD involves various pathophysiological processes such as inflammatory response, oxidative stress, glutamate excitotoxicity, Ca2+ overload, immunosuppression, and cholinergic system dysfunction. Stroke leads to lesions at key sites, such as hippocampal or cerebral white matter lesions and microhemorrhages, resulting in structural and functional disruption of the cortico-subcortical loop, which is the main anatomical mechanism for the development of PSD. Vascular risk factors such as hypertension, diabetes, hyperlipidemia, atrial fibrillation, cerebrovascular disease, heavy smoking, and cellular aging and degeneration are important factors that promote vascular damage and P-amyloid deposition and ultimately lead to the development of PSD. Therefore, interventions targeting vascular risk factors, neurodegenerative factors and their pathophysiological processes are the main measures to prevent and treat PSD. Systematic evaluation and pooled analysis showed that multiple strokes, stroke-related risk factors and stroke complications are significantly associated with PSD, and active post-stroke rehabilitation and secondary prevention are important measures to prevent the development of PSD. Lifestyle modifications such as antithrombotic therapy, control of various risk factors, dietary and nutritional management and functional exercise can prevent PSD directly or indirectly by preventing stroke recurrence. Interventions for vascular risk factors 1. Antihypertensive therapy Antihypertensive therapy is the most widely studied and promising intervention for the prevention of post-stroke cognitive impairment (PSCI) and PSD. However, the preventive effect of antihypertensive therapy on PSD remains controversial due to differences in diagnostic criteria, level of blood pressure control, choice of antihypertensive drugs, and short follow-up periods. A large sample follow-up study in the United Kingdom confirmed that antihypertensive therapy reduced the relative risk of distant PSCI. The magnitude of blood pressure reduction may be an important factor influencing the extent of cognitive improvement with antihypertensive therapy, and this is being further explored in three studies. One of these studies, the Subcortical Small Stroke Secondary Prevention Study (SPS3), will look at the effect of 4 years of intensive BP lowering (<130 mmHg systolic; 1 mmHg=0.133 kPa) versus conventional BP lowering (130-149 mmHg systolic) on the incidence of stroke recurrence and cognitive decline; the Post Stroke Cognitive Decompensation Prevention Trial (PODCAST) will also look at the effect of intensive BP lowering (<130 mmHg systolic; 1 mmHg=0.133 kPa) versus conventional BP lowering (130-149 mmHg systolic) on the incidence of cognitive decline after stroke. The Post Stroke Cognitive Decompensation Prevention Trial (PODCAST) will also look at the long-term effects of intensive (systolic <125 mmHg) versus conventional (systolic <140 mmHg) hypotension on reducing the risk of developing PSD; the Systolic Blood Pressure Intervention Trial (SPRINT) will analyze a subgroup of people with a prior history of cardiovascular disease and look at the effects of 2 hypotensive strategies (systolic <140 mmHg versus systolic <120 mmHg) on the incidence of VaD and on vascular cognitive impairment. The effect of the two antihypertensive strategies (systolic blood pressure <140 mmHg and systolic blood pressure <120 mmHg) on the incidence of VaD and the protective effect on vascular cognitive impairment (VCI) was also investigated. Lipid-lowering therapy Statin therapy has been shown to reduce the risk of PSCI, but pooled analyses and randomized controlled trials (RCTs) have not found a significant improvement in cognitive function in people with cerebrovascular disease. Recent studies have focused on the relationship between the magnitude of lipid lowering and improvement in cognitive function, with PODCAST examining the protective effect of intensive lipid lowering (LDL cholesterol <2 mmol/L) versus conventional lipid lowering (<3 mmol/L) therapy on PSCI. 3. Antiplatelet therapy Antiplatelet therapy is the mainstay of stroke recurrence prevention. The London Stroke Registry follow-up study confirmed that aspirin combined with dipyridamole was associated with a reduced risk of PSCI, and the SPS3 study will also look at the protective effect of aspirin combined with clopidogrel on cognitive function during the 4-year follow-up after lacunar cerebral infarction. 4. Combination therapy In recent years, several studies have investigated the preventive effects of combined vascular risk factor interventions on PSCI. Among them, various combination therapies such as antiplatelet aggregation, antihypertensive and lipid-lowering have been shown to significantly reduce the risk of PSCI. In addition, an RCT in first-time stroke patients showed that intensive interventions for multiple vascular risk factors improved executive and memory function, but a beneficial effect of intensive control of risk factors on cognitive function 1 year after stroke has not been derived, possibly related to a follow-up period of only 1 year and a non-optimal intensive intervention regimen. Lifestyle interventions 1. Diet and nutrition Diet can directly or indirectly influence the occurrence and development of vascular risk factors and may prevent and delay the onset of PSD by reducing stroke sequelae and attenuating ischemic neurological damage. The Mediterranean diet is a very beneficial dietary pattern for human health, and long-term adherence to the Mediterranean diet in individuals at high risk of vascular events significantly improves cognitive function and significantly reduces the incidence of cognitive impairment. A systematic evaluation of 14 retrospective or cross-sectional studies of the association between nutrition and VaD showed that intake of antioxidants (especially vitamins C and E) and lipid-rich fish prevented the occurrence of VaD, but that dietary antioxidant supplementation had no significant effect on cognitive function. In addition, there are conflicting findings on dietary lipid content and insufficient evidence for its prevention of the risk of VaD development. 2. Functional exercise Aerobic exercise improves cognitive function after stroke and may be associated with increased serum brain-derived nerve growth factor expression. Numerous RCTs suggest that functional exercise has a significant improvement in cognitive function, but studies have mostly excluded patients with previous stroke. Marzolini et al. found significant improvements in cognitive function, including attention, visuospatial and executive abilities, and a significant decrease in the prevalence of PSCI after 6 months of aerobic and resistance exercise training in 41 post-stroke patients with motor impairment. Rand et al. found that delayed recall improved to normal levels after 6 months of aerobic and recreational training in people with mild declines in executive function after stroke. A systematic evaluation also confirmed that functional exercise significantly improved post-stroke cognitive function, especially executive function. II. Treatment of PSD Cholinesterase inhibitors Cholinesterase inhibitors can delay cognitive impairment by inhibiting cholinesterase to enhance the effect of acetylcholine, and are the main clinical drugs currently used to treat PSD, including donepezil, galantamine and carboplatin. Numerous clinical studies have confirmed that cholinesterase inhibitors can significantly improve cognitive function in patients with VaD, but not overall neurological function. 1. donepezil Donepezil is the most well-documented cholinesterase inhibitor for the treatment of VaD or PSD (Table 1). A multicenter, open 30-week extension study based on 2 24-week RCTs showed that although donepezil did not improve Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) scores as much as the first 24 weeks, it still resulted in sustained stabilization up to 54 weeks, thus confirming the long-term efficacy of donepezil in improving cognitive impairment. A small sample study showed a significant improvement in Simple Intelligence Checklist (MMSE) scores after 4 weeks of treatment with donepezil in right hemisphere stroke patients and confirmed that this improvement may be related to parietal-frontal neural network remodeling. Another study of 168 CADASIL patients with mildly reduced cognitive function given donepezil for 18 weeks showed an improvement in executive function, although no significant difference was seen in ADAS-Cog scores. The effect of donepezil in overall function remains controversial (Table 1). A 24-week RCT suggested that donepezil significantly improved cognitive function in patients with VaD, but had no significant effect on overall function. In contrast, a small sample of phase II controlled studies showed that donepezil given within 24 h of stroke onset and maintained until 60 d significantly improved neurological regression at 90 d, suggesting that it may be beneficial for overall neurological function after stroke. Another open study in patients with VaD and mixed dementia treated with donepezil for 24 weeks showed that donepezil significantly improved cognitive executive function and confirmed a significant improvement in overall function. 2. cabalactam and galantamine There is still a lack of sufficient evidence for the effectiveness of cabalactam and galantamine in improving cognitive function in patients with VaD or PSD (Table 2). A recent exploratory study showed that carboplatin improved executive function in patients with PSCI. A Cohrane systematic evaluation showed that carboplatin significantly improved cognitive function but not overall function, behavior, or activities of daily living, a finding derived primarily from one of the large sample studies. Previous studies have shown that galantamine has a significant delaying effect on cognitive and overall functional decline in patients with mixed dementia, while it has no significant effect on daily functioning in patients with VaD. The only study with mild to moderate mixed dementia indirectly confirmed that galantamine not only improved cognitive function but also quality of life.The Cochrane systematic evaluation showed that galantamine improved both cognition and overall function in patients with VaD, but with a high incidence of gastrointestinal adverse effects. Glutamate receptor antagonists Memantine improves cognitive function by antagonizing glutamate receptors and reducing excitotoxicity. In addition to being approved for the treatment of AD, memantine has been shown to significantly improve cognitive function in patients with mild to moderate VaD, but again, the improvement in overall neurological function is not significant. Recent experimental animal studies have made some progress, showing in various ways that memantine can reduce neurological damage caused by cerebral ischemia, delay microinfarct development and cognitive impairment, and promote angiogenesis and recovery of sensory and motor functions by increasing brain-derived neurotrophic factor signaling and reducing reactive astrocyte aggregation. These findings provide some basis for the possibility that memantine may improve cognitive function and overall prognosis in PSD. Nimodipine has been shown to significantly improve cognitive function after stroke, and the mechanism may be related to specific action in important cognitive areas such as the cortex, dentate gyrus, and hippocampus, but its efficacy remains controversial. It is currently thought that the timing of administration may influence the efficacy of nimodipine, and that starting treatment in the acute or subacute phase may have a greater cognitive benefit. A recent study is investigating the protective effect of 6 months of nimodipine treatment starting within 7 d from stroke onset on PSCI. Cytarabine Cytarabine improves executive, attentional, and orienting abilities after stroke, and the mechanism may be related to enhanced repair of injured neurons and increased brain levels of acetylcholine, norepinephrine, and dopamine. Recent studies have confirmed that cytarabine delays VCI, but its overall functional effects remain controversial. 349 patients with mild VCI were shown in the IDEALE study to have significantly delayed cognitive decline after 9 months of cytarabine treatment, but failed to improve daily activities. Another RCT including 347 first-time stroke patients confirmed that cytarabine treatment for 12 months significantly improved attention, executive function and spatio-temporal orientation, as well as overall function. However, a recent RCT with a large sample showed that cytarabine did not significantly improve neurological regression and daily activities at 90 d after acute ischemic stroke onset. Antidepressants Post-stroke depression affects patients' cognitive function, and impairment of executive function increases the incidence of geriatric depression. It has been shown that fluoxetine, a 5-hydroxytryptamine reuptake inhibitor, and nortriptyline, a tricyclic antidepressant, improve recovery of motor function and overall neurological function. In addition, fluoxetine improved both cognitive and motor function recovery, sertraline improved executive function in stroke patients, and escitalopram treatment for 12 months significantly improved memory and overall function in stroke patients. It is hypothesized that the mechanisms by which antidepressants improve PSCI, motor and global function may be related to modulation of cholinergic transmission, hippocampal plasticity, and enhanced neuroangiogenesis. Other drugs There are various other drugs that have made progress in the study of VaD or PSD prevention and treatment. Ginkgo biloba extract has some neuroprotective effects. A recent animal experiment on VaD showed that Ginkgo biloba extract attenuated free radical damage and inhibited neuronal apoptosis in the cerebral cortex and hippocampal CA1 region, thereby protecting learning and memory functions. A clinical study including 71 patients with VaD showed that 24 weeks of treatment with Ginkgo biloba extract significantly improved cognitive function and daily activities. Another clinical study also confirmed that cognitive function and cerebral blood flow were significantly improved in VCI patients treated with Ginkgo biloba extract for 3 months. Cerebrolysin injection has been shown to mimic neurotrophic factor function in cognitive protection, and a recent Cochrane evaluation showed that cerebrolysin injection significantly improved not only overall neurological function but also overall cognitive and executive function in patients with VaD. The ARTEMIDA study is evaluating the effect of calf blood deprotein extract injection on improving cognitive function in patients with PSCI. Another RCT will evaluate changes in cognition, mood, and activities of daily living after 24 weeks of application of the herbal medicine MLC901 (containing nine traditional Chinese herbal ingredients) to patients with VCI. In addition, cognitive interventions, repetitive transcranial magnetic stimulation, and acupuncture treatment all have the potential to improve cognitive function in patients with PSD. PSD has a high prevalence in the stroke population and is an independent risk factor for poor outcome in stroke patients, which seriously affects the quality of life and survival time of stroke patients. Therefore, preventing and delaying the onset and progression of PSD is important in improving the quality of life and prolonging the life expectancy of stroke patients. In recent years, a large number of exploratory studies have been conducted on vascular interventions and lifestyle modifications, among which antihypertensive therapy and functional exercise are particularly promising in reducing the risk of PSD, and a Mediterranean-style diet and some antioxidant nutrients may be beneficial in preventing PSD. In terms of treatment, in addition to cholinesterase inhibitors and glutamate receptor antagonists, which have clinical evidence supporting their role in improving cognitive and overall function in PSD, some progress has been made in pharmacotherapeutic studies with nimodipine, cytarabine, antidepressants, and ginkgo biloba extract. However, recent prevention and treatment studies generally lack the credibility of evidence-based medicine, and a number of ongoing large sample studies, including SPRINT (antihypertensive therapy), SPS3 (antihypertensive and antiplatelet therapy), PODCAST (antihypertensive and lipid-lowering therapy), NICE (nimodipine), ICTUS (cytarabine), ARTEMIDA (calf blood deprotein extract injection), and NEURITES (MLC901 in Chinese medicine), all of which will bring further value for exploration. More high-quality clinical studies with PSCI or PSD as study subjects, with cognitive function as the main observation index, with unified PSD diagnostic criteria and cognitive function evaluation scale as evaluation methods, and with large sample RCT and long-term follow-up observation should be conducted in the future.