Zheng, Chengyi

BACKGROUND: The impact of covert cerebrovascular disease on falls in the general population is not well-known. Here, we determine the time to a first fall following incidentally detected covert cerebrovascular disease during a clinical neuroimaging episode. METHODS: This longitudinal cohort study assessed computed tomography (CT) and magnetic resonance imaging from 2009 to 2019 of patients aged >50 years registered with Kaiser Permanente Southern California which is a healthcare organization combining health plan coverage with coordinated medical services, excluding those with before stroke/dementia. We extracted evidence of incidental covert brain infarcts (CBI) and white matter hyperintensities/hypoattenuation (WMH) from imaging reports using natural language processing. We examined associations of CBI and WMH with falls requiring medical attention, using Cox proportional hazards regression models with adjustment for 12 variables including age, sex, ethnicity multimorbidity, polypharmacy, and incontinence. RESULTS: We assessed 241 050 patients, mean age 64.9 (SD, 10.42) years, 61.3% female, detecting covert cerebrovascular disease in 31.1% over a mean follow-up duration of 3.04 years. A recorded fall occurred in 21.2% (51 239/241 050) during follow-up. On CT, single fall incidence rate/1000 person-years (p-y) was highest in individuals with both CBI and WMH on CT (129.3 falls/1000 p-y [95% CI, 123.4–135.5]), followed by WMH (109.9 falls/1000 p-y [108.0–111.9]). On magnetic resonance imaging, the incidence rate was the highest with both CBI and WMH (76.3 falls/1000 p-y [95% CI, 69.7–83.2]), followed by CBI (71.4 falls/1000 p-y [95% CI, 65.9–77.2]). The adjusted hazard ratio for single index fall in individuals with CBI on CT was 1.13 (95% CI, 1.09–1.17); versus magnetic resonance imaging 1.17 (95% CI, 1.08–1.27). On CT, the risk for single index fall incrementally increased for mild (1.37 [95% CI, 1.32–1.43]), moderate (1.57 [95% CI, 1.48–1.67]), or severe WMH (1.57 [95% CI, 1.45–1.70]). On magnetic resonance imaging, index fall risk similarly increased with increasing WMH severity: mild (1.11 [95% CI, 1.07–1.17]), moderate (1.21 [95% CI, 1.13–1.28]), and severe WMH (1.34 [95% CI, 1.22–1.46]). CONCLUSIONS: In a large population with neuroimaging, CBI and WMH are independently associated with greater risks of an index fall. Increasing severities of WMH are associated incrementally with fall risk across imaging modalities.

Introduction While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins. Methods Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins. Results Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 to 53.9%) were not on statins within 6 months prior to the scan. Of those, 12.0% (95% CI 11.7 to 12.3%) were prescribed statins in the next 6 months compared with 9.3% (95% CI 9.1 to 9.4%) in those without CCD, a 2.7% (95% CI 2.4 to 3.1%) absolute increase in statin prescription for those with id-CCD. In adjusted analyses, the presence of id-CCD was only associated with minor increases in statin prescription (CBI or WMD (risk ratio (RR) 1.09, 95% CI 1.05 to 1.13), CBI alone (RR 1.34, 95% CI 1.21 to 1.47), WMD alone (RR 1.05, 95% CI 1.01 to 1.09), and CBI and WMD (RR 1.23, 95% CI 1.12 to 1.35)). Discussion Identification of id-CCD is not associated with substantial changes in statin prescription in routine clinical practice.

Background Covert cerebrovascular disease (CCD) has been shown to be associated with dementia in population‐based studies with magnetic resonance imaging (MRI) screening, but dementia risk associated with incidentally discovered CCD is not known. Methods and Results Individuals aged ≥50 years enrolled in the Kaiser Permanente Southern California health system receiving head computed tomography (CT) or MRI for nonstroke indications from 2009 to 2019, without prior ischemic stroke/transient ischemic attack, dementia/Alzheimer disease, or visit reason/scan indication suggestive of cognitive decline or stroke were included. Natural language processing identified incidentally discovered covert brain infarction (id‐CBI) and white matter disease (id‐WMD) on the neuroimage report; white matter disease was characterized as mild, moderate, severe, or undetermined. We estimated risk of dementia associated with id‐CBI and id‐WMD. Among 241 050 qualified individuals, natural language processing identified 69 931 (29.0%) with id‐WMD and 11 328 (4.7%) with id‐CBI. Dementia incidence rates (per 1000 person‐years) were 23.5 (95% CI, 22.9–24.0) for patients with id‐WMD, 29.4 (95% CI, 27.9–31.0) with id‐CBI, and 6.0 (95% CI, 5.8–6.2) without id‐CCD. The association of id‐WMD with future dementia was stronger in younger (aged <70 years) versus older (aged ≥70 years) patients and for CT‐ versus MRI‐discovered lesions. For patients with versus without id‐WMD on CT, the adjusted HR was 2.87 (95% CI, 2.58–3.19) for younger and 1.87 (95% CI, 1.79–1.95) for older patients. For patients with versus without id‐WMD on MRI, the adjusted HR for dementia risk was 2.28 (95% CI, 1.99–2.62) for younger and 1.48 (95% CI, 1.32–1.66) for older patients. The adjusted HR for id‐CBI was 2.02 (95% CI, 1.70–2.41) for younger and 1.22 (95% CI, 1.15–1.30) for older patients for either modality. Dementia risk was strongly correlated with id‐WMD severity; adjusted HRs compared with patients who were negative for id‐WMD by MRI ranged from 1.41 (95% CI, 1.25–1.60) for those with mild disease on MRI to 4.11 (95% CI, 3.58–4.72) for those with severe disease on CT. Conclusions Incidentally discovered CCD is common and associated with a high risk of dementia, representing an opportunity for prevention. The association is strengthened when discovered at younger age, by increasing id‐WMD severity, and when id‐WMD is detected by CT scan rather than MRI.

Objective This study aimed to examine the relationship between covert cerebrovascular disease, comprised of covert brain infarction and white matter disease, discovered incidentally in routine care, and subsequent Parkinson disease. Methods Patients were ≥50 years and received neuroimaging for non‐stroke indications in the Kaiser Permanente Southern California system from 2009 to 2019. Natural language processing identified incidentally discovered covert brain infarction and white matter disease and classified white matter disease severity. The Parkinson disease outcome was defined as 2 ICD diagnosis codes. Results 230,062 patients were included (median follow‐up 3.72 years). A total of 1,941 Parkinson disease cases were identified (median time‐to‐event 2.35 years). Natural language processing identified covert cerebrovascular disease in 70,592 (30.7%) patients, 10,622 (4.6%) with covert brain infarction and 65,814 (28.6%) with white matter disease. After adjustment for known risk factors, white matter disease was associated with Parkinson disease (hazard ratio 1.67 [95%CI, 1.44, 1.93] for patients <70 years and 1.33 [1.18, 1.50] for those ≥70 years). Greater severity of white matter disease was associated with increased incidence of Parkinson disease(/1,000 person‐years), from 1.52 (1.43, 1.61) in patients without white matter disease to 4.90 (3.86, 6.13) in those with severe disease. Findings were robust when more specific definitions of Parkinson disease were used. Covert brain infarction was not associated with Parkinson disease (adjusted hazard ratio = 1.05 [0.88, 1.24]). Interpretation Incidentally discovered white matter disease was associated with subsequent Parkinson disease, an association strengthened with younger age and increased white matter disease severity. Incidentally discovered covert brain infarction did not appear to be associated with subsequent Parkinson disease. ANN NEUROL 2022;92:620–630

Background: White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for stroke. Nevertheless, the predictive value of these changes when seen incidentally on routinely-obtained neuroimages is unknown. Methods: In this retrospective cohort study, Kaiser Permanente-Southern California health plan enrollees aged ≥ 50 years old with a brain CT or MRI scan between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the index neuroimaging report. We used Cox proportional hazards to estimate the risk of future ischemic stroke associated with the presence of SBI and of WMD, controlling for major stroke risk factors. Results: Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The Table below summarizes the crude stroke incidence rates. The crude hazard ratio (HR) was 3.40 (95% CI 3.25-3.56) for SBI and 2.63 (95% CI 2.54-2.71) for WMD. In the multivariable model controlling for all major stroke risk factors, the effect of SBI was found to be stronger in younger versus older patients and for MRI- versus CT-discovered lesions. With MRI, the average adjusted HR over time was 2.95 (95% CI 2.53-3.44) for those < age 65 and 2.15 (95% CI 1.91-2.41) for those ≥ age 65. With CT scan, the average adjusted HR over time was 2.48 (95%CI 2.19-2.81) for those < age 65 and 1.81 (95% CI 1.71-1.91) for those ≥ age 65. The adjusted HR associated with a finding of WMD was 1.76 (95% CI 1.69-1.82) and was not modified by age or imaging modality. The effect of SBI decreased gradually over time, while the effect of WMD remained constant. Conclusion: Incidentally-discovered SBI and WMD are common in patients ≥ age 50 and are associated with substantial increases in the risk of subsequent symptomatic stroke. The findings may represent an opportunity for stroke prevention.

Background: White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for dementia. Nevertheless, the effects of incidentally-discovered WMD and SBI on routinely-obtained neuroimages is unknown. Methods: In the retrospective cohort study, Kaiser Permanente-Southern California (KPSC) health plan enrollees aged ≥ 50 years old with a brain cross-sectional image (CT or MRI) between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the first qualifying neuroimaging report. Cox proportional hazards regression model was applied to estimate the effects of WMD and SBI on dementia, controlling for major cardiovascular risk factors. Results: Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The table below summarizes the crude dementia incidence rates. The crude hazard ratio (HR) was 3.69 (95% CI 3.58-3.80) for WMD and 2.80 (95% CI 2.68-2.93) for SBI. In the multivariable model controlling for all major cardiovascular risk factors, the effect of WMD on dementia risk was found to be stronger in younger compared to older patients and for CT- compared to MRI-discovered lesions. With CT, the adjusted HR was 3.08 (95% CI 2.84-3.34) for those < age 70 and 1.90 (95% CI 1.83-1.97) for those ≥ age 70. With MRI, the adjusted HR was 2.58 (95% CI 2.31-2.87) for those < age 70 and 1.59 (95% CI 1.45-1.75) for those ≥ age 70. The adjusted HR associated with a finding of SBI was 2.01 (95% CI 1.78-2.32) for patients age <70 and 1.26 (95% CI 1.20-1.32) for patients age ≥70, and was not modified by imaging modality. Conclusion: Incidentally-discovered WMD and SBI are common in patients ≥ age 50 and are associated with substantial increase in the risk of subsequent dementia. The findings may represent an opportunity for dementia prevention.

Introduction: Silent brain infarcts (SBIs) and white matter disease (WMD) are highly prevalent and associated with increased risk of ischemic stroke in patients with traditional stroke risk factors (RFs) in prospective cohort studies. Their frequency and associations with stroke RFs have not been well described in real world populations. Methods: This was a cross-sectional study of patients age ≥ 50 in the Kaiser Permanente-Southern California (KPSC) health system between 2009-2019 with a head CT or MRI for non-stroke indications and no history of ischemic stroke, transient ischemic attack, or dementia. A natural language processing (NLP) algorithm developed at Mayo Clinic and Tufts Medical Center was applied to the KPSC EHR to identify individuals with reported SBIs or WMD. Multivariable Poisson regression with robust error variance was used to estimate risk ratios of demographics, stroke RFs (from the Framingham Stroke Risk Score), and scan modality on the presence of SBIs or WMD. Results: Among 262,875 individuals, the NLP identified 13,154 (5.0%) with SBIs and 78,330 (29.8%) with WMD. Stroke RFs were highly prevalent in this cohort. The majority underwent CTs (74.8%) instead of MRIs as their initial neuroimaging. After adjustment for demographics and RFs, advanced age demonstrated a strong association with increased risk of SBIs and WMD (table). MRI was associated with a reduced risk of reported SBIs (ARR: 0.87, 95% CI 0.83-0.91) and an increased risk of reported WMD (ARR 2.86, 95% CI 2.83-2.90). Despite being prevalent, traditional stroke RFs had weak associations with increased risk of SBIs or increased risk of WMD. Conclusions: Advanced age is strongly associated with incidentally discovered SBIs and WMD on neuroimaging studies obtained in routine care. The development of SBIs and WMD may not be fully attributable to traditional stroke RFs.