Imaging Biomarkers of VCI: A Focused Update.

Vascular cognitive impairment is common after stroke, in memory clinics, medicine for the elderly services, and undiagnosed in the community. Vascular disease is said to be the second most common cause of dementia after Alzheimer disease, yet vascular dysfunction is now known to predate cognitive decline in Alzheimer disease, and most dementias at older ages are mixed. Neuroimaging has a major role in identifying the proportion of vascular versus other likely pathologies in patients with cognitive impairment. Here, we aim to provide a pragmatic but evidence-based summary of the current state of potential imaging biomarkers, focusing on magnetic resonance imaging and computed tomography, which are relevant to diagnosing, estimating prognosis, monitoring vascular cognitive impairment, and incorporating our own experiences. We focus on markers that are well-established, with a known profile of association with cognitive measures, but also consider more recently described, including quantitative tissue markers of vascular injury. We highlight the gaps in accessibility and translation to more routine clinical practice.

Risk of Alzheimer's Disease and Related Dementias in Persons with Glaucoma: A National Cohort Study.

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort. DESIGN: National matched cohort study. PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia. METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for sociodemographic factors and comorbidities. MAIN OUTCOME MEASURES: Alzheimer's disease, VaD, and all-cause dementia identified from nationwide inpatient and outpatient diagnoses through 2018. RESULTS: In 16 million person-years of follow-up, 32 339 persons (10%) with glaucoma and 226 896 controls (7%) were diagnosed with dementia. Persons with glaucoma had increased risks for AD (adjusted HR, 1.39; 95% confidence interval [CI], 1.35-1.43), VaD (1.66; 1.61-1.72), and all-cause dementia (1.57; 1.54-1.59). Among glaucoma subtypes, both primary open-angle and normal-tension glaucoma were associated with increased risk for AD (adjusted HR, 1.31; 95% CI, 1.27-1.36; and 1.28; 1.20-1.36, respectively) and VaD (1.61; 1.54-1.68; and 1.39; 1.28-1.50, respectively), whereas primary angle-closure glaucoma was associated with VaD (1.26; 1.02-1.56) but not AD (0.98; 0.82-1.18). These findings were similar in men and women. All risks were highest in persons diagnosed with glaucoma at ages ≥ 70 years and were not elevated for ages < 60 years. CONCLUSIONS: In this large national cohort, persons with glaucoma had increased risks for AD, VaD, and all-cause dementia, particularly those diagnosed with glaucoma at older ages. Persons with glaucoma may need increased monitoring for dementia to facilitate earlier detection and treatment. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Health Conditions Associated with Alzheimer's Disease and Vascular Dementia.

OBJECTIVE: We examined medical records to determine health conditions associated with dementia at varied intervals prior to dementia diagnosis in participants from the Baltimore Longitudinal Study of Aging (BLSA). METHODS: Data were available for 347 Alzheimer's disease (AD), 76 vascular dementia (VaD), and 811 control participants without dementia. Logistic regressions were performed associating International Classification of Diseases, 9th Revision (ICD-9) health codes with dementia status across all time points, at 5 and 1 year(s) prior to dementia diagnosis, and at the year of diagnosis, controlling for age, sex, and follow-up length of the medical record. RESULTS: In AD, the earliest and most consistent associations across all time points included depression, erectile dysfunction, gait abnormalities, hearing loss, and nervous and musculoskeletal symptoms. Cardiomegaly, urinary incontinence, non-epithelial skin cancer, and pneumonia were not significant until 1 year before dementia diagnosis. In VaD, the earliest and most consistent associations across all time points included abnormal electrocardiogram (EKG), cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss. Atrial fibrillation, occlusion of cerebral arteries, essential tremor, and abnormal reflexes were not significant until 1 year before dementia diagnosis. INTERPRETATION: These findings suggest that some health conditions are associated with future dementia beginning at least 5 years before dementia diagnosis and are consistently seen over time, while others only reach significance closer to the date of diagnosis. These results also show that there are both shared and distinctive health conditions associated with AD and VaD. These results reinforce the need for medical intervention and treatment to lessen the impact of health comorbidities in the aging population. ANN NEUROL 2023;93:805-818.

Developmental priming of early cerebrovascular ageing: Implications across a lifetime.

INTRODUCTION: Neurological conditions such as Alzheimer's disease and stroke represent a substantial health burden to the world's ageing population. Cerebrovascular dysfunction is a key contributor to these conditions, affecting an individual's risk profile, age of onset, and severity of neurological disease. Recent data shows that early-life events, such as maternal health during pregnancy, birth weight and exposure to environmental toxins can 'prime' the vascular system for later changes. With age, blood vessels can become less flexible and more prone to damage. This can lead to reduced blood flow to the brain, which is associated with cognitive decline and an increased risk of stroke and other cerebrovascular diseases. These in turn increase the risk of vascular dementia and Alzheimer's disease. OBJECTIVES: We aim to explore how early life factors influence cerebrovascular health, ageing and disease. METHODS: We have reviewed recently published literature from epidemiological studies, clinical cases and basic research which explore mechanisms that contribute to cerebrovascular and blood-brain barrier dysfunction, with a particularly focus on those that assess contribution of early-life events or vascular priming to subsequent injury. RESULTS: Perinatal events have been linked to acute cerebrovascular dysfunction and long-term structural reorganisation. Systemic disease throughout the lifetime that produce inflammatory or oxidative stress may further sensitise the cerebrovasculature to disease and contribute to neurodegeneration. CONCLUSIONS: By identifying these early-life determinants and understanding their mechanisms, scientists aim to develop strategies for preventing or mitigating cerebrovascular ageing-related issues.

Ethoxyquin, a Lipid Peroxidation Inhibitor, Has Protective Effects against White Matter Lesions in a Mouse Model of Chronic Cerebral Hypoperfusion.

White matter lesions induced by chronic cerebral hypoperfusion can cause vascular dementia; however, no appropriate treatments are currently available for these diseases. In this study, we investigated lipid peroxidation, which has recently been pointed out to be associated with cerebrovascular disease and vascular dementia, as a therapeutic target for chronic cerebral hypoperfusion. We used ethoxyquin, a lipid-soluble antioxidant, in a neuronal cell line and mouse model of the disease. The cytoprotective effect of ethoxyquin on glutamate-stimulated HT-22 cells, a mouse hippocampal cell line, was comparable to that of a ferroptosis inhibitor. In addition, the administration of ethoxyquin to bilateral common carotid artery stenosis model mice suppressed white matter lesions, blood-brain barrier disruption, and glial cell activation. Taken together, we propose that the inhibition of lipid peroxidation may be a useful therapeutic approach for chronic cerebrovascular disease and the resulting white matter lesions.

Prevalence of Concomitant Neurological Disorders and Long-Term Outcome of Patients Hospitalized for Intracerebral Hemorrhage with Versus without Cerebral Amyloid Angiopathy.

BACKGROUND: Patients with intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) are at increased risk of developing epilepsy and cognitive disorders such as Alzheimer's disease (AD), mild cognitive impairment (MCI), and vascular dementia. In a retrospective cohort observation study of patients hospitalized for ICH with CAA versus ICH without CAA, we evaluated the prevalence of neurological comorbidities at admission and the risk of new diagnosis of epilepsy, relevant cognitive disorders, and mortality at 1 year. METHODS: In the TriNetX health research network, adult patients aged ≥ 55 years hospitalized with a diagnosis of ICH were stratified based on presence or absence of concomitant CAA diagnosis. Demographics and medical comorbidities were compared by using χ2 test and Student's t-test. After 1:1 propensity score matching, 1-year survival was assessed with Kaplan-Meier curves. The 1-year risk of new diagnosis of epilepsy, AD, MCI, vascular dementia, and dementia unspecified was assessed with Cox proportional hazards estimate. RESULTS: The study included a total of 1757 patients with ICH and CAA and 53,364 patients with ICH without CAA. Patients with CAA were older compared with those without CAA (74.1 ± 7.5 vs. 69.8 ± 8.8 years, p ≤ 0.001). Compared with ICH without CAA, patients with ICH and CAA had higher baseline prevalence of cerebral infarction (30% vs. 20%), nontraumatic ICH (36% vs. 7%), nontraumatic subarachnoid hemorrhage (14% vs. 5%), epilepsy (11% vs. 6%), and AD (5% vs. 2%) with significance at p < 0.001. After propensity score matching, a total of 1746 patients were included in both cohorts. In the matched cohorts, compared with patients with ICH without CAA, patients with ICH and CAA had lower 1-year all-cause mortality (479 [27%] vs. 563 [32%]; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.71-0.90) and higher risk of new diagnosis of epilepsy (280 [18%] vs. 167 [11%]; HR 1.70; 95% CI 1.40-2.06), AD (101 [6%] vs. 38 [2%]; HR 2.62; 95% CI 1.80-3.80), MCI (85 [5%] vs. 35 [2%]; HR 2.39; 95% CI 1.61-3.54), vascular dementia (117 [7%] vs. 60 [4%]; HR 1.92; 95% CI 1.41-2.62), and dementia unspecified (245 [16%] vs. 150 [9%]; HR 1.70; 95% CI 1.39-2.08). CONCLUSIONS: Among patients admitted for ICH, patients with CAA have lower mortality but have 2-3 times more risk of diagnosis of epilepsy and dementia at 1 year, compared with those without CAA.

The risk of dementia or cognitive impairment in patients with cataracts: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to investigate whether cataract disease is associated with the risk of developing dementia or cognitive impairment. METHODS: A systematic search of the literature in PubMed, the Extracts Database (Embase), the Cochrane Library and the Web of Science databases was performed from the inception data of each database until 1 September 2022. Sensitivity analyses were performed to assess the robustness and reliability of the overall findings. All extracted data were statistically analyzed using Stata software v.16.0. Publication bias was assessed using funnel plots and the Egger test. RESULTS: There were 11 publications included in this study, which consisted of 489,211participants, spanning 10 countries from 2012 to 2022. Aggregation suggested that cataracts were associated with cognitive impairment (odds ratio [OR] = 1.32; 95% CI: 1.21-1.43; I 2 = 45.4.%; p = 0.000). The presence of cataracts is significantly associated with an increased risk of developing all-cause dementia (relative risk [RR] = 1.17; 95% CI: 1.08-1.26; I2 = 0.0%; p = 0.000). In subgroup analyses, having cataracts may increase the risk of Alzheimer's disease (hazard ratio [HR] = 1.28; 95% CI: 1.13-1.45; I2 = 0.0%; p = 0.000) and vascular dementia (HR = 1.35; 95% CI = 1.06-1.73; I2 = 0.0%, p = 0.015). The data from the Egger's test showed no significant evidence of publication bias. CONCLUSIONS: Cataracts are associated with the risk of cognitive impairment and dementia, including Alzheimer's disease, and vascular dementia.

Innate Sleep Apnea in Spontaneously Hypertensive Rats Is Associated With Microvascular Rarefaction and Neuronal Loss in the preBötzinger Complex.

BACKGROUND: Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia. METHODS: To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders: plethysmography and electroencephalographic/electromyographic recordings were used to assess sleep-wake state, breathing parameters, and sleep-disordered breathing; immunocytochemistry was used to assess vascular and neural health; the forced alteration Y maze and Barnes maze were used to assess short- and long-term memories, respectively; and an anesthetized preparation was used to assess baroreflex sensitivity. RESULTS: Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories. CONCLUSIONS: Therefore, we postulate that hypertension induces SA through vascular damage in the respiratory column, culminating in neuronal loss in the inspiratory oscillator. This induction of SA, which, in turn, will independently exacerbate hypertension and neural inflammation, increases the rate of vascular dementia.

Age-related immune alterations and cerebrovascular inflammation.

Aging is associated with chronic systemic inflammation, which contributes to the development of many age-related diseases, including vascular disease. The world's population is aging, leading to an increasing prevalence of both stroke and vascular dementia. The inflammatory response to ischemic stroke is critical to both stroke pathophysiology and recovery. Age is a predictor of poor outcomes after stroke. The immune response to stroke is altered in aged individuals, which contributes to the disparate outcomes between young and aged patients. In this review, we describe the current knowledge of the effects of aging on the immune system and the cerebral vasculature and how these changes alter the immune response to stroke and vascular dementia in animal and human studies. Potential implications of these age-related immune alterations on chronic inflammation in vascular disease outcome are highlighted.

BPSD Patterns in Patients With Severe Neuropsychiatric Disturbances: Insight From the RECAGE Study.

OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD. METHODS: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE. RESULTS: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms. CONCLUSION: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.

Ablation of atrial fibrillation and dementia risk reduction during long-term follow-up: a nationwide population-based study.

AIMS: This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia. METHODS AND RESULTS: We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer's disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer's disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58-0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49-1.50). CONCLUSION: Patients with AF have a higher incidence of all types of dementia, including Alzheimer's disease, vascular dementia, and a mixed type of dementia. Alzheimer's disease is less likely to occur in patients with AF undergoing catheter ablation.

Blood Pressure and Vascular Cognitive Impairment.

High blood pressure (BP) is detrimental to brain health. High BP contributes to cognitive impairment and dementia through pathways independent of clinical stroke. Emerging evidence shows that the deleterious effect of high BP on cognition occurs across the life span, increasing the risk for early-onset and late-life dementia. The term vascular cognitive impairment includes cognitive disorders associated with cerebrovascular disease, regardless of the pathogenesis. This focused report is a narrative review that aims to summarize the epidemiology of BP and vascular cognitive impairment, including differences by sex, race, and ethnicity, as well as the management and reversibility of BP and vascular cognitive impairment. It also discusses knowledge gaps and future directions.

Metabolic Syndrome and Vascular-Associated Cognitive Impairment: a Focus on Preclinical Investigations.

PURPOSE OF REVIEW: Metabolic syndrome is associated with an increased risk of vascular cognitive impairment or, in the more extreme, vascular dementia. Animal models are used to investigate the relationship between pathology and behaviour. This review summarizes the latest understanding of the role of the hippocampus and prefrontal cortex in vascular cognitive impairment, the influence of inflammation in this association while also commenting on some of the latest interventions proposed. RECENT FINDINGS: Models of vascular cognitive impairment and vascular dementia, whether they develop from an infarct or non-infarct base, demonstrate increased neuroinflammation, reduced neuronal function and deficits in prefrontal and hippocampal-associated cognitive domains. Promising new research shows agents and environmental interventions that inhibit central oxidative stress and inflammation can reverse both pathology and cognitive dysfunction. While preclinical studies suggest that reversal of deficits in vascular cognitive impairment models is possible, replication in patients still needs to be demonstrated.

New Onset Poststroke Dementia at one Year in Africans.

BACKGROUND: There is limited information on new onset poststroke dementia (NPSD) in sub-Saharan Africa (SSA). We estimated incidence, cumulative incidence, risk factors and outcome of NPSD at 1 year in Nigerian survivors of a first-ever stroke. METHODS: Hospital-based prospective observational study. Assessments for global cognition, learning, memory, executive and activities of daily life (ADL) functioning were conducted at 3 poststroke timepoints (Baseline, 3- and 12 months). NPSD was ascertained according to the "National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria." Outcomes were assessed using the modified Rankin Scale (mRS), center for epidemiologic studies depression scale (CES-D 10), health related quality of life in stroke patients (HRQOLISP-26) and caregivers strain index (CSI). RESULTS: Among 144 stroke survivors who were free of dementia at baseline, we found a 1-year cumulative incidence of 4.52% (95% C.I = 3.20, 6.39). In multivariate Cox regression analyses, diabetes was associated with NPSD (Hazard Ratio = 2.10, 95% CI = 1.02, 4.35). NPSD at 3 months was independently associated with motor decline [Mean difference (MD) in mRS = 1.6, 95% C.I = 0.9, 2.3)], depression (MD in CES-D = 2.9, 95% C.I = 0.3, 5.4), caregivers burden (MD in CSI = 1.2, 95% C.I = 0.5, 1.8), and poor quality of life (MD in HRQOLISP-26 = -11.2, 95% C.I = -15.7, -6.8) at 1 year. CONCLUSION: Approximately 4.5% of stroke survivors in Nigeria had NPSD at 1 year. Diabetes, which can be prevented, represent a primary prevention target for NPSD and its consequences in SSA.

Systemic infection exacerbates cerebrovascular dysfunction in Alzheimer's disease.

We studied the effects of systemic infection on brain cytokine level and cerebral vascular function in Alzheimer's disease and vascular dementia, in superior temporal cortex (Brodmann area 22) from Alzheimer's disease patients (n = 75), vascular dementia patients (n = 22) and age-matched control subjects (n = 46), stratified according to the presence or absence of terminal systemic infection. Brain cytokine levels were measured using Mesoscale Discovery Multiplex Assays and markers of cerebrovascular function were assessed by ELISA. Multiple brain cytokines were elevated in Alzheimer's disease and vascular dementia: IL-15 and IL-17A were maximally elevated in end-stage Alzheimer's disease (Braak tangle stage V-VI) whereas IL-2, IL-5, IL12p40 and IL-16 were highest in intermediate Braak tangle stage III-IV disease. Several cytokines (IL-1ß, IL-6, TNF-α, IL-8 and IL-15) were further raised in Alzheimer's disease with systemic infection. Cerebral hypoperfusion-indicated by decreased MAG:PLP1 and increased vascular endothelial growth factor-A (VEGF)-and blood-brain barrier leakiness, indicated by raised levels of fibrinogen, were exacerbated in Alzheimer's disease and vascular dementia patients, and also in non-dementia controls, with systemic infection. Amyloid-ß42 level did not vary with infection or in association with brain cytokine levels. In controls, cortical perfusion declined with increasing IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and tumour necrosis factor-α (TNF-α) but these relationships were lost with progression of Alzheimer's disease, and with infection (even in Braak stage 0-II brains). Cortical platelet-derived growth factor receptor-ß (PDGFRß), a pericyte marker, was reduced, and endothelin-1 (EDN1) level was increased in Alzheimer's disease; these were related to amyloid-ß level and disease progression and only modestly affected by systemic infection. Our findings indicate that systemic infection alters brain cytokine levels and exacerbates cerebral hypoperfusion and blood-brain barrier leakiness associated with Alzheimer's disease and vascular dementia, independently of the level of insoluble amyloid-ß, and highlight systemic infection as an important contributor to dementia, requiring early identification and treatment in the elderly population.

Migraine and the risk of dementia: a meta-analysis and systematic review.

OBJECTIVES: To conduct a comprehensive systematic review and meta-analysis to explore the correlation between migraine and the risk of dementia. METHODS: The PubMed, EMBASE, and Cochrane library databases were searched systematically. We selected cohort studies (prospective and retrospective) and case-control studies that reported migraine in patients with dementia, including vascular dementia. The pooled effects were analyzed to evaluate relative risk with 95% confidence intervals. RESULTS: In total, nine studies (two case-control and seven cohort studies) including 291,549 individuals were identified. These studies indicated that people with migraine (relative risk = 1.33; 95% confidence interval: 1.16-1.53) have an increased risk of all-cause dementia. Additionally, the pooled results of four studies showed that migraine is associated with an increased risk of vascular dementia (relative risk = 1.85; 95% confidence interval: 1.22-2.81; P = 0.004). CONCLUSIONS: Data from observational studies suggest that migraine may be a risk factor for dementia, particularly vascular dementia. More studies are warranted to explore the association between migraine and dementia and the potential common pathophysiological mechanisms.

Dementia in Africa: Current evidence, knowledge gaps, and future directions.

In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.

Shared Risk Factors between Dementia and Atherosclerotic Cardiovascular Disease.

Alzheimer's disease is the most common form of dementia, and the prodromal phases of Alzheimer's disease can last for decades. Vascular dementia is the second most common form of dementia and is distinguished from Alzheimer's disease by evidence of previous stroke or hemorrhage and current cerebrovascular disease. A compiled group of vascular-related dementias (vascular dementia and unspecified dementia) is often referred to as non-Alzheimer dementia. Recent evidence indicates that preventing dementia by lifestyle interventions early in life with a focus on reducing cardiovascular risk factors is a promising strategy for reducing future risk. Approximately 40% of dementia cases is estimated to be preventable by targeting modifiable, primarily cardiovascular risk factors. The aim of this review is to describe the association between risk factors for atherosclerotic cardiovascular disease and the risk of Alzheimer's disease and non-Alzheimer dementia by providing an overview of the current evidence and to shed light on possible shared pathogenic pathways between dementia and cardiovascular disease. The included risk factors are body mass index (BMI); plasma triglyceride-, high-density lipoprotein (HDL) cholesterol-, low-density lipoprotein (LDL) cholesterol-, and total cholesterol concentrations; hypertension; diabetes; non-alcoholic fatty liver disease (NAFLD); physical inactivity; smoking; diet; the gut microbiome; and genetics. Furthermore, we aim to disentangle the difference between associations of risk factors in midlife as compared with in late life.

Clinical Trials of New Drugs for Vascular Cognitive Impairment and Vascular Dementia.

Population aging has challenged the treatment of cognitive impairment or dementia. Vascular dementia is the second leading cause of dementia after Alzheimer's disease. Cognitive consequences after ischemic brain injury have been recognized as a preferred target for therapeutic strategies, prompting the search for potential agents. The keyword "vascular dementia" was used to search ClinicalTrials.gov to determine agents represented in phases I, II, III, and IV. The agents were classified on the basis of their mechanisms. Of the 17 randomized controlled trials meeting our inclusion criteria, 9 were completed in the past 10 years, and 8 are ongoing or in the planning stages. We also identified one trial in phase I, nine in phase II, six in phase III, and one in phase IV. Fewer trials of new drugs for improving cognition or ameliorating the behavioral and psychological symptoms of dementia target vascular dementia than Alzheimer's dementia. Drug trials on vascular dementia overlap with drug trials targeting functional outcomes in cerebrovascular disease. International pharmaceutical companies' investment in new drugs targeting VCI and vascular dementia remains insufficient.

Increased risk of all-cause, Alzheimer's, and vascular dementia in adults with migraine in Korea: a population-based cohort study.

BACKGROUND: Studies investigating the association between migraine and dementia have reported inconsistent findings. This study aimed to evaluate whether patients with migraine have an increased risk of dementia compared to individuals without migraine. METHODS: We obtained data from the 2002-2019 Korean National Health Insurance Health Screening Cohort. Non-migraine controls were selected using a 1:1 risk-set matching with a time-dependent propensity score. The main outcome was the development of all-cause dementia, and the secondary outcome was the development of each cause of dementia (Alzheimer's, vascular, mixed or other specified, and unspecified dementia). The incidence rate of dementia was calculated using Poisson regression, and the association between migraine and dementia was evaluated using Cox proportional hazards regression. RESULTS: Among 88,390 participants, 66.1% were female, and the mean baseline age was 55.3 ± 9.4 years. During the study period, dementia cases were identified in 4,800 of the 44,195 patients with migraine and 3,757 of the 44,915 matched controls. The incidence rate of dementia was 139.6 (95% confidence interval [CI], 135.7-143.5) and 107.7 (95% CI, 104.3-111.1) cases per 10,000 person-years in patients with migraine and matched controls, respectively. Patients with migraine had a 1.30 (hazard ratio [HR], 1.30; 95% CI, 1.25-1.35), 1.29 (HR, 1.29; 95% CI, 1.23-1.35), 1.35 (HR, 1.35; 95% CI, 1.19-1.54), 1.36 (HR, 1.36; 95% CI, 1.00-1.83), and 1.30 (HR, 1.30; 95% CI, 1.17-1.45) times higher risk of developing all-cause dementia, Alzheimer's dementia, vascular dementia, mixed or other specified dementias, and unspecified dementia than their matched controls, respectively. CONCLUSION: Our results suggest that migraine is associated with an increased risk of subsequent dementia. Further research is warranted to confirm these findings and to reveal the underlying mechanisms.