Evidence Of Small Vessel Disease Research Articles

Evidence of small vessel disease in patients with transient global amnesia based on the peak width of skeletonized mean diffusivity.

The peak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease. In this study, we aimed to investigate the presence of small vessel disease in patients with transient global amnesia (TGA) using the PSMD. We enrolled 75 patients newly diagnosed with TGA and included 65 age-and sex-matched healthy controls. Diffusion tensor imaging (DTI) was performed using a 3T magnetic resonance imaging scanner. We measured the PSMD based on DTI using the FSL program. This measure was compared between patients with TGA and healthy controls. Additionally, we conducted a correlation analysis to explore the relationship between PSMD and clinical factors. A significant difference in the PSMD between patients with TGA and healthy controls was observed. Patients with TGA exhibited higher a PSMD compared to healthy controls (2.297±0.232 vs. 2.188±0.216 ×10-4 mm2/s, p=0.005). Additionally, patients with TGA but without any vascular risk factors, such as diabetes, hypertension or dyslipidemia, also exhibited higher a PSMD compared to healthy controls (2.278±0.253 vs. 2.188±0.216 ×10-4 mm2/s, p=0.036). The PSMD positively correlated with age (r=0.248, p=0.032); however, it was not associated with duration of amnesia. This finding underscores the feasibility of using PSMD as a marker for detecting small vessel diseases in patients with neurological disorders. Furthermore, our study also implies the presence of small vessel disease may be present in patients with TGA. TGA=transient global amnesia; TIA= transient ischemic attack; PSMD= peak width of skeletonized mean diffusivity; DTI= diffusion tensor imaging.

Motor Function Is Associated with Cerebral Small Vessel Disease and Can Predict Mortality and Poor Functional Outcome

Introduction: The primary objective of this study was to elucidate the predictive role of subtle motor impairment evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III on mortality and functional outcome. The secondary objective was to evaluate the association of motor impairment with small vessel disease (SVD) severity. Methods: We derived data from a Japanese cohort of patients with evidence of SVD who were enrolled from 2015 to 2019, and followed until 2023. The present study included 586 participants who agreed for UPDRS Part III evaluation. The severity of white matter hyperintensities (WMHs) and the presence of lacunes were evaluated. Cox proportional hazard models and multiple logistic regression analysis were used to examine the association between UPDRS Part III score and all-cause death and functional outcome defined by the modified Rankin Scale (mRS) score at the last visit, respectively. Results: The median age was 71 years, and the median UPDRS Part III score was 2. The UPDRS Part III score was associated with the severity of WMH (r = 0.225, p < 0.001) and the number (0, 1, ≥2) of lacunes (p < 0.001). During a mean follow-up period of 4.8 years, 29 patients died. The Cox proportional hazard analysis revealed that high UPDRS Part III scores (≥5) were associated with a higher risk of all-cause death compared to low (score 0) and middle (score 1–4) scores (adjusted hazard ratio 3.04; 95% confidence interval, 1.50–7.34, p = 0.005). In multivariate logistic analysis, high UPDRS Part III scores were associated with poor functional outcome (mRS of ≥3) compared with low and middle scores after adjusting for confounding factors (adjusted odds ratio 1.86; 95% confidence interval 1.02–3.41, p = 0.043). Conclusions: Subtle motor impairment was associated with the severity of WMH and number of lacunes and could predict mortality and poor functional outcome independently of vascular risk factors and severity of WMH and lacunes.

Preliminary evidence of high prevalence of cerebral microbleeds in astronauts with spaceflight experience.

Long-duration spaceflight poses a variety of health risks to astronauts, largely resulting from extended exposure to microgravity and radiation. Here, we assessed the prevalence and incidence of cerebral microbleeds in sixteen astronauts before and after a typical 6-month mission on board the International Space Station Cerebral microbleeds are microhemorrhages in the brain, which are typically interpreted as early evidence of small vessel disease and have been associated with cognitive impairment. We identified evidence of higher-than-expected microbleed prevalence in astronauts with prior spaceflight experience. However, we did not identify a statistically significant increase in microbleed burden up to 7months after spaceflight. Altogether, these preliminary findings suggest that spaceflight exposure may increase microbleed burden, but this influence may be indirect or occur over time courses that exceed 1year. For health monitoring purposes, it may be valuable to acquire neuroimaging data that are able to detect the occurrence of microbleeds in astronauts following their spaceflight missions.

A Case of Medium Vessel Vasculitis on CT

56 years old lady with recent history of Inferior MI, and also found to have Spontaneous coronary artery dissection of RCA found on angiography. She has hypertension and is an ex-smoker. MRI head was previously done showing evidence of small vessel disease and 2 lacunar infarcts. Underlying vasculitis were suspected, therefore specialist suggested further investigations to exclude extra coronary arteriopathy, which led to the CT images we have today.

Neuroimaging in an older adult inpatient psychiatric unit

AimsThis audit aimed to analyse the use of neuroimaging and its effect on treatment in an older adult inpatient psychiatry unit over the period of one year.BackgroundBrain imaging can be used as a diagnostic tool in psychiatry. According to NICE guidelines, structural imaging, such as magnetic resonance imaging (MRI) or computed topography (CT), can be used in the workup for dementia diagnosis in order to exclude non-dementia pathology and identify dementia subtype. This is important in the geriatric population where evidence of small vessel disease has an impact on treatment options and management of polypharmacy.MethodA list of patients from the past year (January to December 2019) was accessed. Patient records were then analysed to see if neuroimaging had been accessed during their admission at The Meadows Hospital, Surrey and Borders Partnership. This included imaging from prior to admission. Analysis was divided into type of imaging, comments and impact on diagnosis.ResultOverall numbers for the audit were small. A total of 74 patients were admitted onto the unit, of which 3 were readmissions. There was missing information for 8 patients, giving a total of 63 patients. CT scans were accessed for 35 patients (56% of total); 3 of these were done during the admission. MRI scans were completed for 21 patients (33%), with one requested during admission. A total of 9 patients (14%) had both CT and MRI scans. Neuroimaging results led to a change in diagnosis for 6 patients (10%). In all cases this reflected the finding of small vessel disease and a change of diagnosis to either vascular dementia or mixed dementia.Diagnoses were also analysed. The Meadows Hospital has 2 dementia wards (male and female) and 1 functional ward (for females). A total of 36 patients (57%) were diagnosed with dementia, of which the biggest groups were: Alzheimer's dementia (13 patients, 36%) and Vascular dementia (11 patients, 31%).ConclusionThe majority of the patients were admitted with established diagnoses and so only a small number had changes made following review of imaging. Good imaging results and reports help to differentiate types of dementia. Although neuroimaging is not gold standard in diagnosing dementia syndromes, it is now an important aspect in the diagnostic pathway. Getting the diagnosis correct will help with treating individuals appropriately and avoid unnecessary prescribing.

Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making.

Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.

Abstract P62: Older Adults With Cerebral Small Vessel Disease Show Increased Levels of Circulating Vascular Endothelial Growth Factor D

Introduction: Cerebral small vessel disease (SVD) resulting from pathological changes in cerebral microvessels is a common precursor of stroke and dementia. Progressive and insidious damage to the cerebral microvasculature may trigger angiogenic processes to promote vessel repair. However, few previous studies have explored the angiogenic response to SVD. In a cohort of older adults with early evidence of SVD, we aimed to examine circulating levels of vascular endothelial growth factor D (VEGF-D)—a secreted glycoprotein with high angiogenic and lymphangiogenic potential—which has previously been linked to heart failure, atrial fibrillation, and ischemic stroke. Methods: Sixty independently living older adults (mean age = 69.7 years; SD = 7.5; age range 55-90 years; 38.3% male) free of dementia or clinical stroke were recruited from the community and underwent venipuncture and brain MRI. Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, Flt-1). MRI changes thought to represent microvascular pathologies (white matter hyperintensities, microbleeds and lacunes) were evaluated and total SVD load was determined using a previously validated score. Multiple linear regression examined the relationship between circulating proangiogenic proteins levels and total SVD load. Results: Moderate/severe white matter hyperintensity burden was identified by Fazekas scale in 40.0% of participants, small lacunes were identified in 13.3% and microbleeds in 6.7%. Simple linear regression revealed a positive relationship between circulating VEGF-D and total SVD score (p = .019), which remained significant in multiple regression controlling for age, sex and Framingham stroke score (p = .017). VEGF-D was significantly positively correlated with VEGF-C (r = .37), Flt-1 (r = .31) and Tie-2 (r = .42). Conclusions: These findings suggest that elevated levels of circulating VEGF-D correspond with greater damage to the cerebral microvasculature in older adults with no history of clinical stroke or dementia. Additional studies are warranted to determine whether activation of systemic proangiogenic growth factors represents an early attempt to rescue the vascular endothelium and repair damage in cerebral SVD.

Small Resistance Artery Disease and ACE2 in Hypertension: A New Paradigm in the Context of COVID-19

Cardiovascular disease causes almost one third of deaths worldwide, and more than half are related to primary arterial hypertension (PAH). The occurrence of several deleterious events, such as hyperactivation of the renin–angiotensin system (RAS), and oxidative and inflammatory stress, contributes to the development of small vessel disease in PAH. Small resistance arteries are found at various points through the arterial tree, act as the major site of vascular resistance, and actively regulate local tissue perfusion. Experimental and clinical studies demonstrate that alterations in small resistance artery properties are important features of PAH pathophysiology. Diseased small vessels in PAH show decreased lumens, thicker walls, endothelial dysfunction, and oxidative stress and inflammation. These events may lead to altered blood flow supply to tissues and organs, and can increase the risk of thrombosis. Notably, PAH is prevalent among patients diagnosed with COVID-19, in whom evidence of small vessel disease leading to cardiovascular pathology is reported. The SARS-Cov2 virus, responsible for COVID-19, achieves cell entry through an S (spike) high-affinity protein binding to the catalytic domain of the angiotensin-converting enzyme 2 (ACE2), a negative regulator of the RAS pathway. Therefore, it is crucial to examine the relationship between small resistance artery disease, ACE2, and PAH, to understand COVID-19 morbidity and mortality. The scope of the present review is to briefly summarize available knowledge on the role of small resistance artery disease and ACE2 in PAH, and critically discuss their clinical relevance in the context of cardiovascular pathology associated to COVID-19.

Functional health and white matter hyperintensities as effect modifiers of blood pressure-lowering on cognitive function and vascular events in older Secondary Prevention of Small Subcortical Strokes trial participants.

To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke. Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living). One thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events). There was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events. Clinicaltrials.gov Identifier: NCT00059306.

Structural network efficiency predicts cognitive decline in cerebral small vessel disease

Cerebral small vessel disease (SVD) is a common disease in older adults and a major contributor to vascular cognitive impairment and dementia. White matter network damage is a potentially important mechanism by which SVD causes cognitive impairment. Earlier studies showed that a higher degree of white matter network damage, indicated by lower global efficiency (a graph-theory measure assessing efficiency of network information transfer), was associated with lower scores on cognitive performance independent of MRI markers for SVD. However, it is unknown whether this global efficiency index is the strongest predictor for cognitive impairment, as there is a wide range of network measures. Here, we investigate which network measure is the most informative in explaining baseline cognitive performance and decline over a period of 8.7 years in SVD. We used data from the Radboud University Nijmegen Diffusion tensor and MRI Cohort (RUN DMC), which included 436 participants without dementia (65.2 ± 8.8 years) but with evidence of SVD on neuroimaging. Binarized and weighted structural brain networks were reconstructed using diffusion tensor imaging and deterministic streamlining. Using graph-theory, we calculated 21 global network measures and performed linear regression analyses, elastic net analysis and linear mixed effect models to compare these measures. All analyses were adjusted for potential confounders (age, sex, educational level, depressive symptoms and conventional SVD MRI-markers (e.g. white matter hyperintensities (WMH), lacunes of presumed vascular origin and microbleeds). The elastic net analyses showed that, at baseline, global efficiency had the strongest association with cognitive index (CI), while characteristic path length showed the strongest association with psychomotor speed (PMS) and memory. Binary local efficiency showed the strongest association with attention & executive function (A&EF). In addition, linear mixed-effect models demonstrated that baseline global efficiency predicts decline in CI (χ2(1) = 8.18, p = 0.004),PMS (χ2(1) = 7.75, p = 0.005), memory (χ2(1) = 27.28, p = 0.000) over time and that binary local efficiency predicts decline in A&EF (χ2(1) = 8.66, p = 0.003) over time. Our results suggest that among all network measures, network efficiency measures, i.e. global efficiency and local efficiency, are the strongest predictors for cognitive functions at cross-sectional level and also predict faster cognitive decline in SVD, which is in line with earlier findings. These findings suggests that in our study sample network efficiency measures are the most suitable surrogate markers for cognitive performance in patients with cerebral SVD among all network measures and MRI markers, and play a key role in the genesis of cognitive decline in SVD.

The Prevalence of Cerebral Microbleeds in Non-Demented Parkinson's Disease Patients.

BackgroundCerebral microbleeds (CMBs) are associated with cerebrovascular risk factors and cognitive dysfunction among patients with Parkinson's disease (PD). However, whether CMBs themselves are associated with PD is to be elucidated.MethodsWe analyzed the presence of CMBs using 3-Tesla brain magnetic resonance imaging in non-demented patients with PD and in age-, sex-, and hypertension-matched control subjects. PD patients were classified according to their motor subtypes: tremor-dominant, intermediate, and postural instability-gait disturbance (PIGD). Other cerebrovascular risk factors and small vessel disease (SVD) burdens were also evaluated.ResultsTwo-hundred and five patients with PD and 205 control subjects were included. The prevalence of CMBs was higher in PD patients than in controls (16.1% vs. 8.8%; odds ratio [OR], 2.126; P = 0.019); CMBs in the lobar area showed a significant difference between PD patients and controls (11.7% vs. 5.9%; OR, 2.234; P = 0.032). According to the motor subtype, CMBs in those with PIGD type showed significant difference from controls with respect to the overall brain area (21.1% vs. 8.9%; OR, 2.759; P = 0.010) and lobar area (14.6% vs. 4.9%; OR, 3.336; P = 0.016). Among PD patients, those with CMBs had higher age and more evidence of SVDs than those without CMBs.ConclusionWe found that CMBs are more frequent in PD patients than in controls, especially in those with the PIGD subtype and CMBs on the lobar area. Further study investigating the pathogenetic significance of CMBs is required.

Structural network efficiency predicts conversion to dementia.

To examine whether structural network connectivity at baseline predicts incident all-cause dementia in a prospective hospital-based cohort of elderly participants with MRI evidence of small vessel disease (SVD). A total of 436 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC), a prospective hospital-based cohort of elderly without dementia with cerebral SVD, were included in 2006. During follow-up (2011-2012), dementia was diagnosed. The structural network was constructed from baseline diffusion tensor imaging followed by deterministic tractography and measures of efficiency using graph theory were calculated. Cox proportional regression analyses were conducted. During 5 years of follow-up, 32 patients developed dementia. MRI markers for SVD were strongly associated with network measures. Patients with dementia showed lower total network strength and global and local efficiency at baseline as compared with the group without dementia. Lower global network efficiency was independently associated with increased risk of incident all-cause dementia (hazard ratio 0.63, 95% confidence interval 0.42-0.96, p = 0.032); in contrast, individual SVD markers including lacunes, white matter hyperintensities volume, and atrophy were not independently associated. These results support a role of network disruption playing a pivotal role in the genesis of dementia in SVD, and suggest network analysis of the connectivity of white matter has potential as a predictive marker in the disease.

Incompleteness of the Circle of Willis Correlates Poorly with Imaging Evidence of Small Vessel Disease. A Population-based Study in Rural Ecuador (the Atahualpa Project)

Studies looking for an association between incompleteness of the Circle of Willis (CoW) and small vessel disease (SVD) markers are scarce and conflicting. We aimed to evaluate this association in an unbiased population-based study conducted in Atahualpa (rural Ecuador). Atahualpa residents 60 years of age or more were identified during a door-to-door survey and invited to undergo magnetic resonance imaging for identification of SVD markers, including white matter hyperintensities (WMHs), strokes, and deep microbleeds. Magnetic resonance imaging (MRA) was used for classifying the CoW according to the presence or absence of one A1 segment of the anterior cerebral artery or one or both P1 segments of posterior cerebral arteries. Of 311 eligible persons, 258 were enrolled. Mean age was 70 ± 8 years, 59% were women, and 74% had a poor cardiovascular health (CVH) status. Of these, 172 patients (67%) had WMH, 40 patients (16%) had SVD-related strokes, and 23 patients (9%) had deep microbleeds. MRA revealed a complete CoW in 157 persons (61%). Persons with SVD markers were older than those without markers (P < .0001). A poor CVH status was noted in 79% of persons with at least 1 SVD marker and in 65% of those with no markers (P = .02). Logistic regression models showed no association of incompleteness of the CoW with any marker of SVD-alone or in combination-after adjusting for age, sex, and CVH status. Lack of association between incompleteness of CoW and SVD markers suggest that genetically determined variants in the intracranial vasculature are not responsible for the high prevalence of SVD among native South American populations.

Infection with Hemotropic Mycoplasma Species in Patients with or without Extensive Arthropod or Animal Contact

PCR amplification targeting the 16S rRNA gene was used to test individuals with and without extensive arthropod and animal contact for the possibility of hemotropic mycoplasma infection. The prevalence of hemotropic mycoplasma infection (4.7%) was significantly greater in previously reported cohorts of veterinarians, veterinary technicians, spouses of veterinary professionals, and others with extensive arthropod exposure and/or frequent animal contact than in a previously reported cohort of patients examined by a rheumatologist because of chronic joint pain or evidence of small-vessel disease (0.7%). Based upon DNA sequence analysis, a Mycoplasma ovis-like species was the most prevalent organism detected; however, infection with "Candidatus Mycoplasma haematoparvum" and a potentially novel, but incompletely characterized, hemotropic Mycoplasma species was also documented. Historical exposure to animals and arthropod vectors that can harbor hemotropic Mycoplasma spp. should be considered during epidemiological investigations and in the evaluation of individual patients.

Is brain health in the eye of the beholder?

Arteriolar disease of the brain manifests itself structurally as lacunar infarcts and leukoaraiosis, and may also lead to cognitive dysfunction. Although the pathogenesis of leukoaraiosis is somewhat controversial, its strong association with vascular risk factors, in particular hypertension, implies a microvascular etiology. These subclinical brain changes and their associated effects on cognition are likely to be associated with microvascular disease in other organs. In the article by Haan et al.1 in this issue of Neurology ®, the association between retinal microvascular changes and cerebral outcomes (i.e., cognitive performance and subclinical brain lesions and volume) is evaluated in the Women's Health Initiative (WHI). In this WHI study, although retinopathy is found infrequently (in 7.6% of 511 participants), it is associated with worsening over 10 years on cognitive assessment with the modified Mini-Mental State Examination (3MSE) and with larger ischemic volumes on brain MRI (using a composite measure of lacunar infarcts and white matter hyperintensities [WMH]). This parallels other epidemiologic studies that have demonstrated associations between retinal microvascular disease and MRI evidence of small vessel disease (lacunar infarcts or WMH)2 and between …

Renal biomarkers

Renal biomarkers

Brain MRI findings in patients with Fabry disease

Background To evaluate the presence of ischemic and hemorraghic lesions in brain MRI of patients with Fabry disease (FD). Methods Brain MRI studies in 46 consecutive patients were evaluated using classic sequences as well as GRE-weighted images, for ischemic lesions and chronic microbleed detection. Of the 36 adult patients (15 males, mean age 31.2 years; 21 females, mean age 41.6 years). All had signs or symptoms of FD but lacked history of stroke or TIA. Results Ten patients under 20 years of age initially presented a normal MRI. One child developed a hyperintense occipital lesion on T2-weighted imaging during control MRI. Sixteen adult patients (44.4%) had brain MRI evidence of small vessel disease in the basal ganglia, corona radiata, thalamus or brainstem, as well as in the periventricular white matter. Patients with MRI abnormalities were older (45.6 vs 30.9 years, p = 0.005), with more vascular risk factors (1.2 vs 0.6 p = 0.043). Three women (mean age 59.5 years) presented deep chronic microbleeds identified by GRE. Moreover, Flair and T2-weighted images revealed white matter disease and deep gray matter involvement. Conclusion 44.4% of adult patients with FD without clinical history of CVA or prior dialysis had evidence of small vessel disease on MRI and 11% showed cerebral microbleeds. FD is a treatable disorder that should be routinely included in the differential diagnosis of ischemic and microhemorraghic lesions in young adults.

MRI Markers of Small Vessel Disease in Lobar and Deep Hemispheric Intracerebral Hemorrhage

MRI evidence of small vessel disease is common in intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral amyloid angiopathy (CAA) or hypertensive vasculopathy would have different distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds. Data were analyzed from 133 consecutive patients with primary supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston criteria. WMH segmentation was performed using a validated semiautomated method. WMH and microbleeds were compared according to site of symptomatic hematoma origin (lobar versus deep) or by pattern of hemorrhages, including both hematomas and microbleeds, on MRI gradient recalled echo sequence (grouped as lobar only-probable CAA, lobar only-possible CAA, deep hemispheric only, or mixed lobar and deep hemorrhages). Patients with lobar and deep hemispheric hematoma had similar median normalized WMH volumes (19.5 cm versus 19.9 cm(3), P=0.74) and prevalence of >or=1 microbleed (54% versus 52%, P=0.99). The supratentorial WMH distribution was similar according to hemorrhage location category; however, the prevalence of brain stem T2 hyperintensity was lower in lobar hematoma versus deep hematoma (54% versus 70%, P=0.004). Mixed ICH was common (23%). Patients with mixed ICH had large normalized WMH volumes and a posterior distribution of cortical hemorrhages similar to that seen in CAA. WMH distribution is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and deep hemorrhages are seen on MRI gradient recalled echo sequence in up to one fourth of patients; in these patients, both hypertension and CAA may be contributing to the burden of WMH.

Associations between Findings on Cranial Magnetic Resonance Imaging and Retinal Photography in the Elderly: The Cardiovascular Health Study

Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.

Small Vessel Disease and General Cognitive Function in Nondisabled Elderly

On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.