As the population ages, the prevalence of dementia and stroke increases. Stroke remains a leading cause of death and disability among older adults, and a substantial proportion of stroke patients have preexisting cognitive impairment or a formal diagnosis of dementia. Observational studies have reported that approximately one-tenth of stroke patients have prestroke dementia,¹ and another study found that 16.3% were already demented before stroke onset.²

However, definitive evidence regarding the efficacy and safety of acute ischemic stroke (AIS) revascularization therapy in patients with premorbid dementia is limited, because these patients have conventionally been excluded from randomized controlled trials.^3,4 Previous studies have indicated that patients with dementia are less likely to receive revascularization therapy and tend to experience poorer outcomes with treatment.⁵ However, available data remain limited and inconsistent. Furthermore, current clinical guidelines provide little direction for managing AIS in patients with preexisting cognitive impairment, leading to significant uncertainty in clinical decision-making.

This study aimed to investigate the clinical characteristics, treatment patterns, and early outcomes of patients with AIS and a prior diagnosis of dementia who underwent intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) based on data collected from eight medical centers.

This retrospective, multicenter, observational study was conducted across eight hospitals affiliated with the Catholic University of Korea. Data were obtained from the Clinical Data Warehouse (CDW), encompassing patient records collected over a 5-year period from November 2018 to November 2023.

The institutional review boards of all the participating centers approved this study. Patients diagnosed with AIS who received revascularization therapy—either IVT, EVT, or both—during the study period were included in the study. Dementia was defined on the basis of documented medical diagnoses and active prescription of anti-dementia medications (donepezil, rivastigmine, galantamine, or memantine) before the index stroke.

For each patient, a comprehensive set of variables was collected by reviewing medical records. The demographic data included age and sex. Stroke-related variables included the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores at admission and discharge, lesion location, and stroke subtype classified according to the TOAST criteria. Treatment-related information included the mode of revascularization therapy (IVT, EVT, or both); time metrics such as onset-to-door time, door-to-treatment time, and total onset-to-treatment time; and the presence or absence of vessel recanalization. For patients with an unclear onset mode, we used the first abnormal time as the onset time.

Radiological assessments included the evaluation of cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) on gradient-echo (GRE) or susceptibility-weighted imaging (SWI) magnetic resonance imaging (MRI) sequences. The clinical outcomes included the occurrence of hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and mortality within 3 months of the index stroke. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Study (ECASS) criteria.

Given the limited sample size, the statistical analyses were restricted to descriptive methods, and continuous variables summarized as means or medians with ranges, and categorical variables are expressed as absolute frequencies and percentages.

Among the 1,379 patients who underwent revascularization therapy for AIS during the study period, 13 (0.94%) were identified as cognitively impaired individuals receiving anti-dementia medication. Of these, 11 had Alzheimer’s disease and 2 had mild cognitive impairment (MCI) under anti-dementia treatment. The mean age of the dementia group was 83 years (range, 72–94 years), and eight patients (61.5%) were female. The median NIHSS score at presentation was 9.

Most patients (84.6%) presented with strokes of unclear onset, including wake-up strokes, and events witnessed by caregivers who were unable to determine the exact onset time. The mean onset-to-door time was 142 minutes (range, 21–555 minutes), and the mean door-to-treatment time was 120 minutes (Table 1).

Regarding revascularization therapy, 11 patients underwent EVT alone, while 2 received a combination of IVT and EVT.

Based on the TOAST classification, six patients had cardioembolic strokes and seven had large vessel occlusions. The stroke lesions were distributed as follows: right middle cerebral artery (MCA; n=7), left MCA (n=3), bilateral MCAs (n=1), and posterior circulation (n=2).

Radiological evaluation using GRE or SWI MRI sequences revealed cerebral microbleeds (CMBs) in two patients and cortical superficial siderosis (CSS) in one patient. No CMBs or CSS were observed in the remaining 10 patients.

Recanalization was achieved in 10 of the 13 patients. HT occurred in six patients (46%), including three (23%) with symptomatic intracranial hemorrhage (Fig. 1). Notably, none of the three patients who failed to achieve recanalization developed hemorrhagic transformation. Four patients (31%) died within 3 months, and none achieved favorable functional outcomes at discharge (mRS ≤2). Five patients (38%) had poor baseline functional status before stroke onset (mRS=2 in three patients, mRS=3 in one, and mRS=4 in one).

This study revealed that patients with pre-existing dementia rarely undergo revascularization therapy for AIS. Among patients with AIS who received revascularization therapy, only 0.94% were taking anti-dementia medications. This proportion is strikingly low considering that approximately 9.7% of patients with transient ischemic attack or stroke in a previous study had prestroke dementia. ⁶ Several factors may explain this disparity, including diagnostic uncertainty due to unclear symptom onset, concerns about poor prognosis, and a perceived higher risk of complications, such as hemorrhagic transformation.

Previous studies have also reported that patients with dementia are less likely to receive revascularization therapy or stroke care.⁵ In our cohort, most patients (84%, 11/13) presented with strokes of unclear onset, including three wake-up strokes and eight unwitnessed events identified by caregivers. These patients are often unable to report the exact time of onset, which leads to their ineligibility for treatment. The proportion of unclear-onset strokes in our study was notably higher than that reported in a previous study, in which 36% of patients identified within 24 hours had an unclear onset (13.6% unwitnessed and 22.6% wake-up strokes).⁷ This discrepancy may reflect reduced stroke awareness among individuals with dementia and their greater likelihood of living alone or in care facilities where symptom recognition and timely hospital arrival are often delayed. These factors may have contributed to the lower rates of revascularization therapy in this population.

The delayed door-to-treatment time observed in our study may also reflect difficulties in obtaining accurate clinical histories from elderly patients with cognitive impairment, which complicates the determination of the onset time. In addition, part of the study period overlapped with the COVID-19 pandemic, which may have contributed to delays in seeking or accessing acute stroke care.

Our cohort exhibited a high rate of hemorrhagic transformation (46%), with 23% of patients being symptomatic. This rate is higher than that reported in major clinical trials, such as the MR CLEAN trial (6–7%).⁸ None of our patients achieved favorable functional outcomes at discharge, and 31% died within 3 months. These poor outcomes likely reflect both the high rate of hemorrhagic complications and poor baseline functional status—five patients in our series had a premorbid modified Rankin Scale score ≥2.

Previous studies have shown that among patients treated within 4.5 hours, those with premorbid dementia did not exhibit significantly higher rates of hemorrhage or mortality than those without dementia. However, these patients are less likely to achieve favorable outcomes and are less frequently treated with IVT.⁹ Similarly, a large U.S. inpatient database study found that patients with dementia were less likely to undergo endovascular thrombectomy, while IVT rates were comparable between the groups. In-hospital mortality was higher in the dementia group, although it appeared to be primarily driven by greater stroke severity. Among the patients who underwent endovascular thrombectomy, those with dementia also showed a higher risk of hemorrhagic complications.¹⁰

Taken together, these findings suggest that, while premorbid dementia may not directly increase the risk of hemorrhage or death, patients with dementia tend to have poorer functional outcomes and are less likely to receive revascularization therapy. Because our study was a descriptive case series without a control group, direct comparison with prior studies is limited. It remains uncertain whether the poor outcomes in patients with dementia are primarily attributable to age and comorbidities or to an intrinsic vulnerability associated with dementia.

This study has several limitations. First, this was a retrospective observational study rather than a prospective study. Nonetheless, eligible cases were identified from consecutively collected data across eight tertiary centers, which enhanced the representativeness of the sample. Second, dementia was defined based on a documented diagnosis and use of anti-dementia medications. Therefore, patients with untreated or undiagnosed dementia were excluded. The duration of medication use was not predefined and was inconsistently recorded; however, the inclusion of medication use as a criterion was intended to enhance the diagnostic specificity. Third, this study analyzed a small number of patients (n=13) without a matched non-dementia comparison group, limiting the statistical inference. Future studies should include larger prospectively collected datasets with matched controls to enable robust comparative analyses. Moreover, the small sample size and descriptive design limit the generalizability of our findings.

Given that approximately 10% of adults aged ≥65 years have dementia and that dementia is a known stroke risk factor, the finding that only 0.94% of the 1,379 patients receiving revascularization therapy were prescribed anti-dementia medication suggests that dementia patients are substantially underrepresented in the reperfusion treatment cohorts. This may reflect underdiagnosis, incomplete medical record review, or exclusion of patients with historical but discontinued medication use. Therefore, larger prospective studies focusing on acute stroke management in patients with dementia are warranted.

In conclusion, patients with pre-existing dementia comprise a small proportion of those receiving revascularization therapy for AIS. Their clinical course is often complicated by an unclear onset, delayed treatment, higher hemorrhagic risk, and poor functional recovery. Therefore, efforts to improve the timely recognition, diagnostic precision, and treatment safety in this vulnerable population are urgently required.