Higher Vascular Burden Research Articles

Distinct effects of blood pressure parameters on Alzheimer’s and vascular markers in 1,952 Asian individuals without dementia

BackgroundRisk factors for cardiovascular disease, including elevated blood pressure, are known to increase risk of Alzheimer’s disease. There has been increasing awareness of the relationship between long-term blood pressure (BP) patterns and their effects on the brain. We aimed to investigate the association of repeated BP measurements with Alzheimer’s and vascular disease markers.MethodsWe recruited 1,952 participants without dementia between August 2015 and February 2022. During serial clinic visits, we assessed both systolic BP (SBP) and diastolic BP (DBP), and visit-to-visit BP variability (BPV) was quantified from repeated measurements. In order to investigate the relationship of mean SBP (or DBP) with Alzheimer’s and vascular markers and cognition, we performed multiple linear and logistic regression analyses after controlling for potential confounders (Model 1). Next, we investigated the relationship of with variation of SBP (or DBP) with the aforementioned variables by adding it into Model 1 (Model 2). In addition, mediation analyses were conducted to determine mediation effects of Alzheimer’s and vascular makers on the relationship between BP parameters and cognitive impairment.ResultsHigh Aβ uptake was associated with greater mean SBP (β = 1.049, 95% confidence interval 1.016–1.083). High vascular burden was positively associated with mean SBP (odds ratio = 1.293, 95% CI 1.015–1.647) and mean DBP (1.390, 1.098–1.757). High tau uptake was related to greater systolic BPV (0.094, 0.001–0.187) and diastolic BPV (0.096, 0.007–0.184). High Aβ uptake partially mediated the relationship between mean SBP and the Mini-Mental State Examination (MMSE) scores. Hippocampal atrophy mediated the relationship between diastolic BPV and MMSE scores.ConclusionsEach BP parameter affects Alzheimer’s and vascular disease markers differently, which in turn leads to cognitive impairment. Therefore, it is necessary to appropriately control specific BP parameters to prevent the development of dementia. Furthermore, a better understanding of pathways from specific BP parameters to cognitive impairments might enable us to select the managements targeting the specific BP parameters to prevent dementia effectively.

Effects of Physical Activity, Vascular Burden and Clinical Diagnosis on White Matter Integrity

AbstractBackgroundAlzheimer’s disease (AD) is the most common type of dementia. Both degenerative and vascular pathology tend to contribute to dementia as AD coexists with single or multiple cardiovascular risk factors (vascular burden). Modifiable lifestyle factor such as physical activity has been associated with lower vascular burden (VB) and a lower risk of dementia. To test whether physical activity characterised as being inactive or active helped preserve white matter microstructure in a sample consisting of healthy controls and patients from the clinical AD continuum (mild cognitive impairment to dementia) with either low or high VB.Method213 participants were recruited from three memory clinics and were classified as being either physically active (n = 113) or inactive (n = 100) based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) questionnaire. Voxel‐wise tract‐based spatial statistics (TBSS) was carried out using a set of 5000 permutations and threshold‐free cluster enhancement (TFCE) to find significant clusters for fractional anisotropy (FA), axial diffusivity (AxD), mean diffusivity (MD) and radial diffusivity (RD).ResultParticipants who were physically active had higher FA and lower AxD, MD and RD values relative to the inactive participants. Changes in indices of WM integrity were widespread across the brain covering mainly association and projection tracts but a few commissural tracts. A three‐way interaction effect between Group × Physical Activity × VB was found for FA that was present in mainly projection tracts with a rightward asymmetry along with some association and commissural tracts. Post hocs revealed greater FA in physically active patients with high VB compared with inactive patients with high VB in projection and association/limbic tracts with a rightward asymmetry. Furthermore, the patients with high VB showed higher FA in bilateral projection fibers and cerebellar regions compared with inactive controls with high VB.ConclusionTBSS analysis revealed that high risk patients such as those with high VB achieved the maximum benefit by being physically active as it led to a much greater preservation of white microstructure relative to controls with high VB. This preservation of white matter microstructure was only observed in patients but not in controls.

The effect of physical activity on white matter integrity in aging and prodromal to mild Alzheimer's disease with vascular comorbidity.

Physical activity is a modifiable lifestyle factor that has been previously associated with reduced vascular burden and reduced risk of dementia. This study tested whether physical activity (i.e., being inactive vs. active) contributed to preservation of white matter microstructure in healthy aging controls and patients in prodromal to mild Alzheimer's disease with low/high vascular burden. A total of 213 participants were recruited from memory clinics. They were classified as being either physically active (n = 113) or inactive (n = 100) based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) questionnaire. Diffusion-weighted images were acquired for all participants and pre-processed based on a standard protocol. A factorial design using voxel-wise tract-based spatial statistics (TBSS) was adopted, with 5,000 permutations and threshold-free cluster enhancement (TFCE), to identify significant clusters for fractional anisotropy (FA), axial diffusivity (AxD), mean diffusivity (MD), and radial diffusivity (RD). Clusters of higher FA and lower AxD, MD, and RD values were found for physically active compared with inactive participants that were widespread covering mainly association and projection tracts but also some commissural tracts. A three-way Group × Physical Activity × Vascular Burden interaction effect was found for FA mostly in a variety of projection tracts with a right predominance, and some commissural and association tracts. Post hoc analyses revealed higher FA in patients with high vascular burden who were physically active compared with those patients with high vascular burden who were inactive mainly in projection and association/limbic tracts with a right predominance. Additionally, higher FA was observed in physically active patients with high vascular burden as compared with physically inactive controls with high vascular burden, mainly in bilateral projection fibers and cerebellar regions. Voxel-wise TBSS analysis revealed better preservation of white matter microstructure that was prominent in the high-risk group such as the patients with high vascular burden, specifically those who were physically active. The beneficial effects of physical activity on white matter microstructure were not observed in the controls.

Management of vascular risk in people with multiple sclerosis at the time of diagnosis in England: A population-based study

Background: Vascular management in People with Multiple Sclerosis (PwMS) is important given the higher vascular burden than the general population, associated with increased disability and mortality. Objectives: We assessed differences in the prevalence of type 2 diabetes and hypertension; and the use of antidiabetic, antihypertensive and lipid-lowering medications at the time of the MS diagnosis. Methods: This is a population-based study including PwMS and matched controls between 1987 and 2018 in England. Results: We identified 12,251 PwMS and 72,572 matched controls. PwMS had a 30% increased prevalence of type 2 diabetes (95% confidence interval (CI) = 1.19, 1.42). Among those with type 2 diabetes, PwMS had a 56% lower prevalence of antidiabetic usage (95% CI = 0.33, 0.58). Prevalence of hypertension was 6% greater in PwMS (95% CI = 1.05, 1.06), but in those with hypertension, usage of antihypertensive was 66% lower in PwMS (95% CI = 0.28, 0.42) than controls. Treatment with lipid-lowering medications was 63% lower in PwMS (95% CI = 0.54, 0.74). PwMS had a 0.4-mm Hg lower systolic blood pressure (95% CI = −0.60, −0.13). 3.8% of PwMS were frail. Conclusion: At the time of diagnosis, PwMS have an increased prevalence of vascular risk factors, including hypertension and diabetes though paradoxically, there is poorer treatment. Clinical guidelines supporting appropriate vascular assessment and management in PwMS should be developed.

Abstract 15676: Sex Differences in Leg Microvascular Arteriolar Function in Patients With Limb Ischemia

Introduction: There are known sex differences in peripheral artery disease (PAD) symptom presentation with women manifesting atypical symptoms and a higher vascular burden. Women are also more prone to periprocedural complications possibly due to sex-specific endothelial dysfunction and microvascular impairment. There is a critical need to understand sex specific differences in microvascular function to improve outcomes for women with PAD. Hypothesis: Lower limb arteriolar flow induced dilation (FID) will be significantly reduced in women, compared to men. Methods: Combined muscle and fat tissue were obtained from the affected leg in patients undergoing revascularization due to PAD. Arterioles were dissected, cannulated, and suspended in a physiological chamber at a stable intraluminal pressure. FID was assessed at increasing intraluminal pressure gradients. A subsample of vessels underwent arteriolar dilation with ACh with and without L-NAME, and SNP. Results: We quantified arteriolar FID in 24 arterioles (7=not viable) from 18 patients undergoing revascularization due to PAD (age 60.2 + 7.4, 44%=F, 61%=Black). Heterogeneity was observed in FID with significantly reduced response observed in women. FID in women at 60 cmH 2 O was 24.7 + 20.5%, compared to 52.6 + 28.0% in men, p=.05, and AUC was 69.0 + 66.8 in women, compared to 147.6 + 82.0 in men (p=.07). Findings were similar in both muscle and adipose arterioles. Vessels treated with Ach responded similar to FID. Vessels treated with L-NAME and SNP showed variable blunted response. Conclusions: Women had more impairment in arteriolar function compared to men, providing insight into sex dimorphism in the PAD population. Findings indicated that FID in arterioles is mostly nitric oxide dependent, although patient and sex specific changes in vascular smooth muscle signaling/function are present. This study support the need to develop microvascular and sex specific interventions for patients with PAD.

Liberating older adults from the bonds of vascular risk factors: What is their impact on financial capacity in amnestic mild cognitive impairment?

There is a pressing need to clarify whether vascular risk factors (VRFs) are related to the heterogeneous cognitive performance found in mild cognitive impairment (MCI) and whether the number of VRFs relates to financial capacity impairment in patients with amnestic MCI (aMCI). A total of 112 participants were divided into three groups: patients with single-domain aMCI, patients with multiple-domain aMCI, and healthy controls (HCs), while taking into consideration whether participants had a diagnosis of one VRF or disease, or more than one VRF or disease. Patients with aMCI with VRFs (one and more than one VRF) and HCs did not differ significantly in age, education, and sex. Mini-Mental State Examination, 15-item Geriatric Depression Scale, and Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS) were administered to all groups. Diagnosis (P <0.001) and VRFs (P=0.006) showed significant main effects on LCPLTAS but no interaction (P=0.654). Patients with aMCI with high vascular burden were more frequently of the multiple-domain subtype, whereas patients with no vascular burden were more frequently of the single-domain subtype. A larger vascular burden is correlated with lower LCPLTAS scores. Vascular burden plays an important role in the heterogeneity of aMCI by impairing financial capacity.

Adherence to Mediterranean diet and subsequent cognitive decline in men with cardiovascular disease

ABSTRACT Backgrounds and aims: Evidence from recent years highlighted the importance of the Mediterranean diet for brain health. We investigated the association between adherence to Mediterranean diet and change in cognitive functions two decades later in patients with cardiovascular disease (CVD). Methods: Participants were men with a history of CVD, who previously participated in the Bezafibrate Infarction Prevention (BIP) trial between 1990 and 1997, had a food diary record, and underwent cognitive evaluations 14.6 ± 1.9 years (T1) and 19.9 ± 1.0 years after baseline (T2) as part of the BIP Neurocognitive study (n = 200, mean age at 57.3 ± 6.3 years). Adherence to the Mediterranean diet was determined from the self-administered 4-day food diary record, with patients categorized into high, middle and poor levels of adherence if they received >5, 4–5 and <4 points, respectively. Cognitive function was assessed using the NeuroTrax computerized battery. Linear mixed models were applied. Results: Among the 200 patients, 52 (26%) had poor adherence, 98 (49%) had middle adherence and 50 (25%) had high levels of adherence to the Mediterranean diet. Those categorized to the poor adherence level had poorer cognitive function at T1 compared to the other groups. Additionally, poor vs. high level of adherence was associated with a greater decline in overall cognitive performance [z-score = −0.23 and 95% confidence interval (CI), −0.43;−0.04; p = 0.021] and in visual spatial functions (−0.46 95% CI, −0.86;−0.06; p = 0.023). Conclusion: This study stresses the possible role of the Mediterranean diet in men with a high vascular burden and may set the ground for future intervention to reduce their risk for cognitive decline.

Vascular burden and APOE ε4 are associated with white matter microstructural decline in cognitively normal older adults

White matter microstructure can be measured with diffusion tensor imaging (DTI). While increasing age is a predictor of white matter (WM) microstructure changes, roles of other possible modifiers, such as cardiovascular risk factors, APOE ε4 allele status and biological sex have not been clarified.We investigated 665 cognitively normal participants from the Baltimore Longitudinal Study of Aging (age 50–95, 56.7% female) with a total of 1384 DTI scans. WM microstructure was assessed by fractional anisotropy (FA) and mean diffusivity (MD). A vascular burden score was defined as the sum of five risk factors (hypertension, obesity, elevated cholesterol, diabetes and smoking status). Linear mixed effects models assessed the association of baseline vascular burden on baseline and on rates of change of FA and MD over a mean follow-up of 3.6 years, while controlling for age, race, and scanner type. We also compared DTI trajectories in APOE ε4 carriers vs. non-carriers and men vs. women.At baseline, higher vascular burden was associated with lower FA and higher MD in many WM structures including association, commissural, and projection fibers. Higher baseline vascular burden was also associated with greater longitudinal decline in FA in the hippocampal part of the cingulum and the fornix (crus)/stria terminalis and splenium of the corpus callosum, and with greater increases in MD in the splenium of the corpus callosum. APOE ε4 carriers did not differ from non-carriers in baseline DTI metrics but had greater decline in FA in the genu and splenium of the corpus callosum. Men had higher FA and lower MD in multiple WM regions at baseline but showed greater increase in MD in the genu of the corpus callosum. Women showed greater decreases over time in FA in the gyrus part of the cingulum, compared to men.Our findings show that modifiable vascular risk factors (1) have a negative impact on white matter microstructure and (2) are associated with faster microstructural deterioration of temporal WM regions and the splenium of the corpus callosum in cognitively normal adults. Reducing vascular burden in aging could modify the rate of WM deterioration and could decrease age-related cognitive decline and impairment.

Abstract 17226: Increased Risk of Heart Failure Associated With Left Atrial Remodeling Without Known Atrial Fibrillation

Background: Atrial fibrillation (AF) significantly increases risk for heart failure (HF) and independently increases mortality and adverse in-hospital outcomes in HF patients. Validated clinical risk scores (ARC2H) can predict HF in patients with AF, but are limited in application as AF is frequently clinically silent or undetected. However, AF may be preceded by significant preclinical remodeling (left atrial enlargement (LAE) or excessive atrial ectopy (EAE)). Whether LAE and EAE are associated with HF prior to AF is unclear. Method(s): We analyzed consecutive adults &gt;65 years with outpatient echocardiography or Holter at 11 Ontario community cardiology clinics (2010-2017). Exclusions were history of AF, anticoagulation, pacemaker/ICD/ILR, and prosthetic valve. Using linked administrative databases, we assessed 5-year rates of HF (primary) and incident AF and death (secondary) associated with LAE and EAE and among subgroups (M vs. F; &lt;75 vs. &gt;75; CHADS-VASC 0-2 vs. 3-6). Competing risks cox proportional hazards estimated adjusted hazard of HF for severe LAE: &gt;47mm (M);&gt;52mm (F)) or increased APBs/hour (EAE: &gt;30) or both LAE and EAE, adjusting for age, vascular comorbidities and left ventricular (LV) dysfunction. Results: In 28,261 adults (mean 73+/-6 years), direct age-adjusted survival was reduced for those with severe LAE and EAE. 5-year rates of HF were increased for severe (8.8%) vs. moderate (3.5%) and mild (1.4%) LAE and for those with excessive (3.8%) vs. normal (2.5%) ectopy. For both LAE and EAE, those &gt;75 and with a CHADS score 3-6 showed marked increases in HF at 5 years compared to &lt;75 (LAE: 10.6% vs. 7.9%; EAE: 4.3% vs. 1.9%) and CHADS score 0-2 (LAE:21.4% vs. 6.6%; EAE: 8.9% vs. 2.4%). Severe LAE increased hazard of HF 2-fold (HR=2.07; p&lt;.0001), and incident AF over 3-fold (HR= 3.43; p&lt;.0001) and EAE increased hazard of HF (HR=1.31; p&lt;.0001) and incident AF (HR=1.13; p&lt;.0001). Those with both LAE and EAE showed an over 3-fold increased hazard of HF (HR=3.28; p&lt;.0014). Conclusions: Severe LAE and EAE without known AF are associated with increased risk of HF and AF after adjusting for LV dysfunction, particularly for those &gt;75 and with high vascular burden. These data have implications for risk stratification, AF screening, and trials for HF prevention in individuals with left atrial remodeling.

Serum uric acid and subsequent cognitive performance in patients with pre-existing cardiovascular disease.

High serum uric acid (UA) levels are associated with numerous vascular risk factors, and vascular disease, that predispose patients to cognitive impairment, yet UA is also a major natural antioxidant and higher levels have been linked to slower progression of several neurodegenerative disease. In-order to test the association between UA and subsequent cognitive performance among patients that carry a high vascular burden, UA levels were determined by calorimetric enzymatic tests in a sub-cohort of patients with chronic cardiovascular disease who previously participating in a secondary prevention trial. After an average of 9.8±1.7 years, we assessed cognitive performance (Neurotrax Computerized Cognitive Battery) as well as cerebrovascular reactivity (CVR) and common carotid intima-media thickness (IMT). Among 446 men (mean age 62.3±6.4 yrs) mean UA levels were 5.8±1.1 mg/dL. Adjusted linear regression models revealed that low UA levels (bottom quintile) were associated with poorer cognitive performance. Adjusted differences between the bottom quintile and grouped top UA quintiles were (B coefficient±SE) −4.23±1.28 for global cognitive scores (p = 0.001), −4.69±1.81 for memory scores (p = 0.010), −3.32±1.43 for executive scores (p = 0.020) and −3.43±1.97 for visual spatial scores (p = 0.082). Significant difference was also found for attention scores (p = 0.015). Additional adjustment for impaired CVR and high common carotid IMT slightly attenuated the relationship. Stronger UA effect on cognitive performance was found for older (age>65) patients with significant age interaction for global cognitive score (p = 0.016) and for executive (p = 0.018) and attention domains (p<0.001). In conclusion, we demonstrate that low UA levels in patients with preexisting cardiovascular disease are associated with poorer cognitive function a decade later. These findings lend support to the hypothesis that oxidative stress may be involved in the pathogenesis of age-associated cognitive impairment.

Cerebrovascular disease, amyloid plaques, and dementia.

Amyloid plaques are depositions of amyloid β (Aβ) protein in the cerebral parenchyma and considered as one of the neuropathological diagnostic hallmarks of Alzheimer’s disease (AD).1 Cerebrovascular disease (CVD) is also highly prevalent among the elderly and is commonly found in patients with AD.2 Autopsy studies conducted during the past 2 decades show that amyloid plaques frequently coexist with CVD, and the 2 may interact to modulate the risks and expression of clinical dementia.2 Neuropathological examinations show that between 6% and 47% individuals with dementia had coexisting AD and CVD pathologies (Table).3–20 Indeed, mixed pathologies may account for the majority of dementia cases (38%).11 View this table: Table. Pathology Findings in Dementia Although autopsy study is considered the gold standard for determining the underlying pathology of dementia, it has inherent limitations with correlating pathological and clinical findings. In particular, uncertainties exist with regard to the temporal relationship between the development of brain lesions and dementia syndrome because of the time lag between dementia onset and autopsy. Moreover, the exact severity or extent of certain manifestations of CVD, in particular, white matter changes (WMC), is difficult to quantify in autopsy studies.21 Also, heterogeneity in the definition of CVD lesions (eg, lacunar infarct) might contribute to inconsistency in assessments between neuropathologists.21 Clinical in-vivo study investigating the relationship between amyloid plaques and cognitive impairment has only been made possible a decade ago with the advent of amyloid imaging, such as Carbon-11-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET). Other amyloid ligands, such as flutemetamol (GE-067), florbetaben (BAY-94–9172, AV-1), and florbetapir (AV-45) have also become available to the market in recent years.22 Amyloid PET can detect comorbid amyloid deposition in patients with high vascular burden.23 We reviewed the potential interactions between CVD and amyloid plaques …

Mild cognitive impairment in obstructive sleep apnea

INTRODUCTION Obstructive sleep apnea (OSA) causes sleep disruption and intermittent nocturnal hypoxemia, which can lead to daytime sleepiness and cognitive deficits. Cognitive deficits reported in individuals suffering from OSA can be severe enough to warrant a diagnosis of mild cognitive impairment (MCI). However, the frequency of MCI in individuals with OSA is unknown and factors associated with co-morbid MCI and OSA need to be investigated. Objectives: Determine the frequency and subtypes of MCI in subjects with OSA and identify demographic and clinical variables associated with co-morbid MCI and OSA. Materials and methods Fifty-one subjects with OSA (apnea- hypopnea index 10; mean age: 60.13 9.48 yrs) and 51 healthy controls (mean age: 61.82 9.49 yrs), matched for sex and education, underwent an overnight polysomnography and a comprehensive neuropsychological assessment. MCI was defined as: 1) objective evidence of cognitive decline; and 2) no major impact of cognitive deficits in activities of daily living. MCI subtypes were categorized as nonamnestic single domain, amnestic single domain, nonamnestic multiple domains and amnestic multiple domains. Group difference in the proportion of MCI was assessed using a ÷ test. Subjects with co-morbid OSA and MCI were compared to subjects with OSA alone on respiratory, demographic, questionnaire, and polysomnographic variables using Student t-tests. Results MCI was found in 37% (19/51) of OSA subjects. In contrast, only 13% (7/51) of controls had MCI ( ÷ = 7.43, dl = 1, p 0.01). Eight (42%) of the 19 patients with comorbid OSA and MCI met the criteria for nonamnestic single domain (6 with impaired attention and executive functions and 2 with impaired visuospatial abilities), two (11%) for amnestic single domain, four (21%) for nonamnestic multiple domains and five (26%) for amnestic multiple domains. Subjects with co-morbid OSA and MCI showed a lower education level (t (52) = 5.17, p 0.01) and a higher score on the vascular burden index (t (23) = -2.07, p 0.05) compared to patients with OSA alone. No difference was found between these two groups for respiratory and polysomnographic variables. Conclusion Results showed that OSA subjects have higher risk of developing MCI compared to control subjects. Nonamnestic MCI subtypes with attention/executive dysfunctions were predominant in OSA. Low education level and high vascular burden were also associated with the presence of MCI among OSA subjects. Future studies are needed to assess the effects of co- morbid MCI and OSA on the risk of converting to dementia. Acknowledgements Supported by the Canadian Institutes of Health Research and the Fonds de recherche du Quebec e Sante

The nature of episodic memory deficits in MCI with and without vascular burden

This study measured episodic memory deficits in individuals with mild cognitive impairment (MCI) as a function of their vascular burden. Vascular burden was determined clinically by computing the number of vascular risk factors and diseases and neuroradiologically by assessing the presence and severity of white matter lesions (WML). Strategic memory processes were measured with free recall and temporal contextual memory tasks requiring self-initiated retrieval. Nonstrategic memory retrieval processes were appraised with a five-choice recognition procedure. Results showed that MCI participants with high vascular burden displayed impairment of strategic memory processes, whereas MCI participants with no vascular burden showed impairment of both strategic and nonstrategic memory processes. A similar pattern was found whether vascular burden was measured using a clinical index of vascular risk profile or whether it was measured neuroradiologically by assessing the extent and severity of subcortical WML. However, the effect of WML on memory differed as function of level of education, used here as a proxy for cognitive reserve. Among participants with MCI, those who had higher education and no WML were the least memory impaired. The study also examined memory as a function of whether patients later progressed to dementia after a three-year follow-up. When examining progressors’ performance, strategic and nonstrategic processes were both impaired in progressors with no concomitant vascular conditions, whereas progressors with a high vascular burden showed less impairment of nonstrategic than strategic processes. Overall, results indicate that the presence of vascular burden in MCI is associated with selective impairment of strategic memory processes.

Impact of Vascular Risk Factors and Diseases on Cognition in Persons with Mild Cognitive Impairment

Background/Aim: To investigate the impact of vascular burden (assessed by the number of vascular risk factors and diseases) on the cognition of persons with amnestic mild cognitive impairment (aMCI). Methods: This study included 145 participants; 68 meeting criteria for amnesic single-domain or multiple-domain MCI and 77 matched controls. Four cognitive domains were assessed: executive functions, processing speed, episodic memory and general cognitive functioning. Results: A larger vascular burden among aMCI is correlated with lower performance in the executive domain. In addition, persons with aMCI with high vascular burden were more frequently of the multiple domain subtype, whereas persons with no vascular burden were more frequently of the single domain subtype. Conclusion: Our findings suggest that the combined effect of multiple vascular risk factors and diseases increases the amount of executive impairment in persons with aMCI. Vascular burden may play an important role in the heterogeneity of aMCI by impairing cognitive functions other than memory.

Contribution of vascular pathology to the clinical expression of dementia

Vascular lesions in the brain are common with advancing age; however, the independent and cumulative contributions of postmortem vascular lesions to antemortem cognitive status are not well established. We examined association of six vascular lesions (large infarcts, lacunar infarcts, leukoencephalopathy, microinfarcts, cribriform changes, and cerebral amyloid angiopathy) with antemortem diagnoses of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in 190 older adults from an autopsy series. We also developed a summary score based on three macroscopic vascular lesions: large infarcts (0, 1, and >or=2), lacunar infarcts (0, 1, and >or=2), and leukoencephalopathy (none, mild, and moderate-to-severe). Sixty-eight percent of cases had vascular lesions. Only leukoencephalopathy was associated with dementia (odds ratio (OR) 3.5, 95% CI 1.0-12.4), and only large infarcts were associated with VaD (OR 4.3, 95% CI 1.2-15.4). The vascular score was associated with dementia (OR 1.6, 95% CI 1.2-2.3), AD (OR 1.5, 95% CI 1.0-2.1) and VaD (OR 2.0, 95% CI 1.4-3.0). Leukoencephalopathy, large infarcts, and higher vascular burden is associated with the clinical expression of dementia and subtypes.