Secondary thalamic atrophy related to brain infarction may contribute to post-stroke cognitive impairment.

BACKGROUND AND PURPOSE: The thalamus is a key brain hub that is globally connected to many cortical regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or cognitive correlates. This study investigates associations between thalamic volumes and post-stroke cognitive function. METHODS: Participants with non-thalamic brain infarcts (3-42 months) underwent MRI and cognitive testing. Focal infarcts and thalami were traced manually. In cases with bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics were extracted using a standardized and previously validated neuroimaging pipeline. Age and gender-matched healthy controls provided normal comparative thalamic volumes. Thalamic atrophy was considered when the volume exceeded 2 standard deviations greater than the controls. RESULTS: Thalamic volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.5 cc, p < 0.001) and right (4.4 ± 1.4 vs. 5.5 ± 0.6 cc, p < 0.001) thalamic volumes in the controls. After controlling for head-size and global brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume (ß= -0.069, p=0.024). Left thalamic atrophy correlated significantly with poorer cognitive performance (ß = 4.177, p = 0.008), after controlling for demographics and infarct volumes. CONCLUSIONS: Our results suggest that the remote effect of infarction on ipsilateral thalamic volume is associated with global post-stroke cognitive impairment.

A Primary Care Agenda for Brain Health: A Scientific Statement From the American Heart Association.

A healthy brain is critical for living a longer and fuller life. The projected aging of the population, however, raises new challenges in maintaining quality of life. As we age, there is increasing compromise of neuronal activity that affects functions such as cognition, also making the brain vulnerable to disease. Once pathology-induced decline begins, few therapeutic options are available. Prevention is therefore paramount, and primary care can play a critical role. The purpose of this American Heart Association scientific statement is to provide an up-to-date summary for primary care providers in the assessment and modification of risk factors at the individual level that maintain brain health and prevent cognitive impairment. Building on the 2017 American Heart Association/American Stroke Association presidential advisory on defining brain health that included "Life's Simple 7," we describe here modifiable risk factors for cognitive decline, including depression, hypertension, physical inactivity, diabetes, obesity, hyperlipidemia, poor diet, smoking, social isolation, excessive alcohol use, sleep disorders, and hearing loss. These risk factors include behaviors, conditions, and lifestyles that can emerge before adulthood and can be routinely identified and managed by primary care clinicians.

Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. METHODS: One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute-subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. RESULTS: Multiple linear regression analyses were completed. Although larger infarcts (ß=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (ß=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (ß=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. CONCLUSIONS: In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Office- and Bedside-based Screening for Cognitive Impairment and the Dementias: Which Tools to Use, Interpreting the Results, and What Are the Next Steps?

Elderly patients and their families are concerned about the patients' cognitive abilities, and cognitive screening is an efficient diagnostic tool, as long as clinicians administer the screens in a standardized manner and interpret the screen results accurately. The following brief summary reviews commonly used screening instruments and provides information about how to interpret screening test results. It concludes by showing how cognitive screening fits into a four-step process (Education, Screening, Follow-up, and Referral) of how to respond to patients with cognitive concerns.

The validity, reliability and clinical utility of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease.

BACKGROUND/AIMS: To evaluate the psychometric properties of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease (SVD). METHODS: 40 SVD patients and 40 matched controls were recruited. Concurrent and criterion validity, inter-rater and test-retest reliability, internal consistency of the HK-MoCA were examined and clinical observations were made. RESULTS: Performance on the HK-MoCA was significantly predicted by both executive (beta = 0.23, p = 0.013) and non-executive (beta = 0.64, p < 0.001) composite scores. It differentiated SVD patients from controls (area under the curve = 0.81, p < 0.001) with an optimal cutoff at 21/22. Reliability, internal consistency and clinical utility were good. CONCLUSION: The HK-MoCA is a useful cognitive screening instrument for use in SVD patients.

Gray matter atrophy in patients with ischemic stroke with cognitive impairment.

BACKGROUND AND PURPOSE: Patients with ischemic stroke are at risk for developing vascular cognitive impairment ranging from mild impairments to dementia. MRI findings of infarction, white matter hyperintensities, and global cerebral atrophy have been implicated in the development of vascular cognitive impairment. The present study investigated regional gray matter volume differences between patients with ischemic stroke with no cognitive impairment and those with impairment in at least one domain of cognitive function. METHODS: Ninety-one patients with ischemic stroke participated. Detailed neuropsychological testing was used to characterize cognitive functioning in 7 domains: orientation, attention, working memory, language, visuospatial ability, psychomotor speed, and memory. High-resolution T1-weighted 3-dimensional fast-spoiled gradient recalled structural MRIs were processed using optimized voxel-based morphometry techniques while controlling for lesions. Whole brain voxelwise regional differences in gray matter volume were assessed between patients with stroke with no impaired cognitive domains and patients with stroke with at least one impaired cognitive domain. Logistic regression models were used to assess the contribution of demographic variables, stroke-related variables, and voxel-based morphometry results to classification of cognitive impairment group membership. RESULTS: Fifty-one patients had no impairments in any cognitive domain and 40 patients were impaired in at least one cognitive domain. Logistic regression identified significant contributions to cognitive impairment groups for demographic variables, stroke-related variables, and cognitive domain performance. Voxel-based morphology results demonstrated significant gray matter volume reductions in patients with stroke with one or more cognitive domain impairment compared with patients with stroke without cognitive impairment that was seen mostly in the thalamus with smaller reductions found in the cingulate gyrus and frontal, temporal, parietal, and occipital lobes. These reductions were present after controlling for group differences in age, education, stroke volume, and laterality of stroke. The addition of voxel-based morphometry-derived thalamic volume significantly improved a logistic regression model predicting cognitive impairment group membership when added to demographic variables, stroke-related variables, and cognitive domain performance. CONCLUSIONS: These results suggest a central role for the thalamus and lesser roles for other cortical regions in the development of cognitive impairment after ischemic stroke. Indeed, consideration of thalamic volumes adds significant information to the classification of cognitive impaired versus nonimpaired groups beyond information provided by demographic, stroke-related, and cognitive performance measures.

National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards.

BACKGROUND AND PURPOSE: One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. METHODS: The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular cognitive impairment. RESULTS: The results of these discussions are reported herein. CONCLUSIONS: The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress.

Volumetric magnetic resonance imaging correlates of the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment neuropsychology protocols.

BACKGROUND: Vascular cognitive impairment (VCI) refers to the entire spectrum of cognitive dysfunction attributable to vascular changes in the brain. The objective of this study is to evaluate magnetic resonance imaging (MRI) correlates of performance on the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) VCI neuropsychology protocols. METHOD: Fifty ischemic stroke patients and 50 normal elderly persons completed the VCI protocols and MRI. Relationships between the four cognitive domains (executive/activation, language, visuospatial, and memory) and three protocol (60-, 30-, and 5-min) summary scores with MRI measures of volumes of white matter hyperintensities (WMH) and global brain and hippocampal atrophy were assessed using linear regression. RESULTS: All cognitive domain scores were associated with WMH volume and, with the exception of language domain, with global atrophy. Additional relationships were found between executive/activation and language domains with left hippocampal volume, visuospatial domain with right hippocampal volume, and memory domain with bilateral hippocampal volumes. All protocol summary scores showed comparable relationships with WMH and hippocampal volumes, with additional relationships found between the 60- and 30-min protocols with global brain volume. CONCLUSIONS: Performance on the NINDS-CSN VCI protocols reflects underlying volumetric brain changes implicated in cognitive dysfunctions in VCI.

Predictors of survival in African American patients with AD, VaD, or stroke without dementia.

BACKGROUND: A hospital-based cohort of African American patients in the Chicago area with AD, vascular dementia (VaD), or stroke without dementia (SWD) were followed for up to 7 years. OBJECTIVE: To describe and analyze predictors of survival in this cohort. METHODS: Proportional hazards regression models were used to analyze risk of death in 113 patients with AD (53 deaths), 79 patients with VaD (31 deaths), and 56 patients with SWD (14 deaths). RESULTS: Patients with AD who were older and had more years of education and lower Barthel ADL scores were at higher risk of death. Patients with VaD who were taking antihypertensive medication were at higher risk of death; those who were taking aspirin or antiplatelet/anticoagulant medication were at lower risk of death; and higher diastolic blood pressure was protective against death. Risk factors for death in the SWD group were older age, having ever been a smoker, and history of atrial fibrillation. Differences in survival across the three groups were not significant after adjusting for age and clinical dementia rating. CONCLUSIONS: Results in patients with VaD support the use of antiplatelet therapy for persons with VaD and suggest that optimal blood pressure may be higher in cognitively compromised poststroke patients than persons in the general population.

Cognitive and functional decline in African Americans with VaD, AD, and stroke without dementia.

OBJECTIVE: To compare the rates of cognitive and functional decline in African American patients diagnosed at baseline with vascular dementia (VaD) (n = 79), AD (n = 113), or stroke without dementia (SWD) (n = 56) and followed for up to 7 years with annual neuropsychological and other examinations. METHODS: Study patients were diagnosed using established criteria for dementia and were administered cognitive screening, functional screening, and neuropsychological measures. Baseline dementia severity was rated using the Clinical Dementia Rating Scale. Random effects modeling was used to examine rates of decline and to compare the rates of decline in the three groups. RESULTS: Both patients with VaD and those with AD showed significant cognitive and functional decline during follow-up; patients with VaD declined at a slower rate than patients with AD; and patients diagnosed with SWD at baseline did not show cognitive or functional decline during follow-up. CONCLUSIONS: Patients with VaD decline at a slower rate than patients with AD. Patients who do not meet criteria for dementia soon after stroke may not be at high risk for developing dementia. Future studies are needed to follow VaD patients with longitudinal, specialized MR protocols, concurrent neuropsychological examinations, and neuropathologic examination to determine possible neuroimaging predictors of progressive cognitive and functional decline and to assess the contribution of Alzheimer's pathology to decline in patients diagnosed with VaD.

The Black Seventh-Day Adventist exploratory health study.

African Americans are at high risk for stroke and dementia. Modifications of lifestyle, however, might lower this risk. The Seventh-Day Adventist (SDA) Church encourages both spiritual adherence and a healthy lifestyle. Members are encouraged to exercise and are discouraged from smoking, drinking alcoholic or caffeinated beverages, or eating meat. The present study describes an exploratory project in 2 Black SDA congregations (N = 82) designed to characterize the lifestyle, dietary, and spiritual health habits of these congregations, and to test the feasibility of collecting such information in the Black SDA community at large. Three separate data collection methods are described and evaluated. Data demonstrate that the sample differs significantly from the African-American community at large in dietary, lifestyle, and spiritual health habits. The Black SDA community represents a unique opportunity to test the effects of diet, lifestyle, and spirituality on risk for stroke and dementia.

The influence of subclinical cardiovascular disease and related risk factors on cognition in type 2 diabetes mellitus: The DHS-Mind study.

We hypothesized that measures of coronary artery calcified plaque (CAC) collected at baseline from the Diabetes Heart Study (DHS) would explain associations between cognition and diabetes collected at follow-up approximately 7 years later. The DHS is a sibling study of cardiovascular disease (CVD) in a cohort with a high prevalence of type 2 diabetes (~80%). Associations between baseline CAC and cognitive performance were tested using generalized estimating equations and mixed effects models to adjust for familial relationships. Diabetes status was associated (p<0.05) with poorer performance on tests of verbal memory, processing speed, and semantic fluency adjusting for age, sex, education, and hypertension status. As hypothesized, including CAC in the statistical model attenuated this association. Additionally, CAC and fasting glucose predicted performance in tasks not associated with diabetes status in this study (Stroop Task, Phonemic Fluency). These results confirm work attributing the heterogeneity of cognitive outcomes in type 2 diabetes to subclinical risk factors that combine to affect different aspects of brain function. Importantly, these results imply that risk factor intervention should begin before comorbidities, particularly CVD, become clinically apparent.

Diagnosis and management of vascular cognitive impairment.

Accurate diagnosis of vascular cognitive impairment (VCI) is important but may be difficult. VCI diagnoses depend on determinations of the presence of both cognitive impairment and cerebrovascular disease (CVD), temporal causal links between cognitive impairment and CVD, and the presence or absence of other potential contributors to cognitive impairment, such as Alzheimer's disease (AD). Diagnostic criteria differ across currently utilized systems, resulting in widely differing VCI prevalence rates. Also, current systems may not be able to differentiate "pure" VCI from "mixed" AD and CVD. National Institute of Neurological Disorders and Stroke harmonization criteria for VCI have been developed for study and validation to help bridge gaps in our understanding of VCI diagnosis. VCI management begins with atherogenic risk factor control. Current VCI treatment options demonstrate statistical improvement but not consistent global clinical efficacy. Future clinical trials should concentrate on both primary risk factor control and development of new therapeutic agents to treat patients already diagnosed with VCI.

Vascular cognitive impairment.

Vascular cognitive impairment encompasses a spectrum of clinically defined syndromes ranging from vascular cognitive impairment-no dementia, to vascular dementia. The underlying cerebrovascular pathology includes both overt infarction as well as rarefaction of gray and white matter. Alzheimer's pathology may coexist with vascular pathology. Diagnosis rests on identifying acquired cognitive impairment in the setting of documented cerebrovascular disease, based on clinical presentation and neuroimaging; MRI is more sensitive than CT. The course can be stepwise or gradually progressive. The clinical picture is typically dominated by deficits in executive function rather than the short-term memory deficit typical of Alzheimer's disease. No specific therapies exist, but treatment with anticholinesterase agents and N-methyl-d-aspartate antagonists may result in clinical improvement. Prevention remains paramount, with early recognition of populations at risk and early and aggressive management of risk factors, including hypertension, dyslipidemia, diabetes, and tobacco use as well as antithrombotic therapy, in appropriate populations.

Longitudinal changes in white matter following ischemic stroke: a three-year follow-up study.

Information on longitudinal changes in white matter after stroke is limited. The aim of the present study was to quantitatively investigate longitudinal changes in the microstructural integrity of non-lesioned white matter at 1-3 years following ischemic stroke. In a sample of 80 ischemic stroke patients, we obtained diffusion tensor imaging (DTI) measures of fractional anisotropy (FA), an apparent measure of white matter integrity, in radiologically normal-appearing white matter at baseline and 3 years of follow-up. Mixed model regression analysis results showed a significant improvement in FA from baseline during the first 2 years of follow-up that stabilized by the third year of follow-up. These results demonstrate a long-term improvement in apparent white matter integrity following ischemic stroke that continues, at least, into the second year following the insult.

The pattern of neuropsychological deficits in Vascular Cognitive Impairment-No Dementia (Vascular CIND).

We examined the pattern of neuropsychological deficits in Vascular Cognitive Impairment-No Dementia (Vascular CIND) by comparing the cognitive and behavioral performance of 41 post-stroke Vascular CIND patients to that of 62 post-stroke patients with no cognitive impairment (NCI). Neuropsychological test scores were grouped into seven cognitive and four behavioral domains, then converted to standardized, weighted principle component scores (PCS) for each domain. Multivariate logistic regression models built on cognitive domains found the immediate recall and psychomotor domains to best predict diagnostic group membership. In a separate model limited to behavioral data, the depressed mood domain best predicted group membership. The combination of immediate memory deficits, psychomotor slowness and depression have also been found in Vascular Dementia (VaD), suggesting that the pattern of deficits in Vascular CIND and VaD neuropsychological deficits are similar. This cognitive and behavioral pattern similarity supports the hypothesis that Vascular CIND lies on a continuum between NCI and VaD.