Brain health assessment. An exploratory review of tools related to its cognitive dimension.

Background: Brain health is an evolving concept and relates to physical and mental health, social well-being, productivity, creativity. Brain health has several dimensions (cognitive, motor, functional, social, and emotional), and should be recognized as one top global priorities of health policies. The purpose of this paper is to provide a summary of tools developed for assessing the cognitive dimension of brain health in the out-patient services. Methods: A literature search on PubMed was performed (from inception to May 31, 2023). We identified cognitive tests, functional and psychological scales, and focused on screening tools specifically proposed to characterize cognition within the construct of brain health, comparing them with common global screening tests. Results: Among 1947 records, we identified 17 cognitive screening tools used in the context of brain health assessment, of which four were ad hoc developed: Brain Health Assessment (BHA), Brain Health Test (BHT), Brain Health Test-7 (BHT-7), and The Cogniciti Brain Health Assessment. The four tests have administration time ranging from 4 to 30 min, and different administration methods (paper-and-pencil or tablet-based). All four tools assess memory and other cognitive domains. Specific cut-offs have been identified for BHT and BHT-7, while the other tools have automated scoring systems. All but one test also assess other dimensions. Compared to commonly used cognitive screening tests, the brain health tools are less widely used, translated, and validated. Conclusions: The concept of brain health is new and requires further validation of tools for its assessment, especially for the cognition dimension.

Etiologic reclassification of cryptogenic stroke after implantable cardiac monitoring and computed tomography angiography re-assessment.

INTRODUCTION: Different mechanisms may underlie cryptogenic stroke, including subclinical atrial fibrillation (AF), nonstenotic carotid plaques (NCP), and aortic arch atherosclerosis (AAA). In a cohort of cryptogenic stroke patients, we aimed to: (1) evaluate the prevalence of subclinical AF, NCP, and AAA, and reclassify the etiology accordingly; (2) compare the clinical features of patients with reclassified etiology with those with confirmed cryptogenic stroke. METHODS: Data of patients hospitalized for cryptogenic stroke between January 2018 and February 2021 were retrospectively analyzed. Patients were included if they received implantable cardiac monitoring (ICM) to detect subclinical AF. Baseline computed tomography angiography (CTA) was re-evaluated to assess NCP and AAA. Since aortic plaques with ulceration/intraluminal thrombus were considered pathogenetic during the initial workup, only patients with milder AAA were included. Stroke etiology was reclassified as "cardioembolic", "atherosclerotic", or "mixed" based on the detection of AF and NCP/AAA. Patients with "true cryptogenic" stroke (no AF, ipsilateral NCP, or AAA detected) were compared with those with reclassified etiology. RESULTS: Among 63 patients included, 21 (33%) were diagnosed with AF (median follow-up time of 15 months), 12 (19%) had ipsilateral NCP, and 6 (10%) had AAA. Stroke etiology was reclassified in 30 patients (48%): cardioembolic in 14 (22%), atherosclerotic in 9 (14%), and mixed in 7 (11%). Patients with true cryptogenic stroke were younger compared to those with reclassified etiology (p = 0.001). DISCUSSION: One or more potential covert stroke sources can be recognized in half of the patients with a cryptogenic stroke through long-term cardiac monitoring and focused CTA re-assessment.

Incipient chronic traumatic encephalopathy in active American football players: neuropsychological assessment and brain perfusion measures.

BACKGROUND AND AIMS: Chronic traumatic encephalopathy (CTE) is a degenerative disease caused by repetitive traumatic brain injury (TBI). Because CTE can be definitely diagnosed only post-mortem, it would be important to explore clinical and radiological correlates of CTE and TBI. The aims of this study were to assess (1) the relationship between the neuropsychological profile of active American football players and the traumatic load; (2) whether traumatic brain injury associated with American football activity has a specific cerebral perfusion pattern; and (3) whether this perfusion pattern correlates with neuropsychological performances. METHODS: In 20 American football players [median age [25th-75th percentile] 25.0 [21.6-31.2] years, all males], we evaluated history, traumatic load and symptoms using the TraQ (Trauma Questionnaire), and cognitive performances on neuropsychological tests. Brain perfusion was estimated using arterial spin labeling MRI and compared to a group of 19 male age-matched (28.0 [24.8-32.3] years) healthy subjects. RESULTS: We found different cognitive performances between American football players stratified according to field position and career length. Linemen had poorer executive, verbal, and visual performances; a career > 7 years was associated with poorer verbal fluency performances. American football players had statistically significant reduced cerebral blood flow values in sensory-motor areas in comparison with healthy controls. Poorer neuropsychological performances correlated with lower perfusion in specific brain areas. CONCLUSIONS: Our study seems to confirm that CTE in American football players is influenced by the field position and the career length, and correlates with lower cognitive performances linked to lower perfusion in specific brain areas.

Prediction of post-stroke cognitive impairment by Montreal Cognitive Assessment (MoCA) performances in acute stroke: comparison of three normative datasets.

BACKGROUND: Cognitive assessment in acute stroke is relevant for identifying patients at risk of persistent post-stroke cognitive impairment (PSCI). Despite preliminary evidence on MoCA accuracy, there is no consensus on its optimal score in the acute stroke setting to predict PSCI. AIMS: (1) To explore whether the application of different normative datasets to MoCA scores obtained in the acute stroke setting results in variable frequency of patients defined as cognitively impaired; (2) to assess whether the normality cut-offs provided by three normative datasets predict PSCI at 6-9 months; (3) to calculate alternative MoCA cut-offs able to predict PSCI. METHODS: Consecutive stroke patients were reassessed at 6-9 months with extensive neuropsychological and functional batteries for PSCI determination. RESULTS: Out of 207 enrolled patients, 118 (57%) were followed-up (mean 7.4 ± 1.7 months), and 77 of them (65%) received a PSCI diagnosis. The application of the normality thresholds provided by the 3 normative datasets yielded to variable (from 28.5% to 41%) rates of patients having an impaired MoCA performance, and to an inadequate accuracy in predicting PSCI, maximizing specificity instead of sensitivity. In ROC analyses, a MoCA score of 22.82, adjusted according to the most recent normative dataset, achieved a good diagnostic accuracy in predicting PSCI. CONCLUSIONS: The classification of acute stroke patients as normal/impaired based on MoCA thresholds proposed by general population normative datasets underestimated patients at risk of persistent PSCI. We calculated a new adjusted MoCA score predictive of PSCI in acute stroke patients to be further tested in larger studies.

A nationwide survey of Italian Centers for Cognitive Disorders and Dementia on the provision of care for international migrants.

BACKGROUND: More than 500,000 dementia cases can be estimated among migrants living in Europe. There is the need to collect "real world" data on the preparedness of healthcare services to support the inclusion of migrants in the public health response to dementia. The present study aimed (i) to estimate the number of migrants referred to Italian memory clinics (Centers for Cognitive Disorders and Dementia [CCDDs]) and (ii) to identify possible barriers and resources for the provision of diversity-sensitive care. METHODS: A survey of all Italian CCDDs was conducted between December 2020 and April 2021. An online questionnaire was developed to obtain information on the number of migrants referred to Italian CCDDs in 2019, the challenges encountered in the diagnostic approach, and possible facilitators in the provision of care. RESULTS: Overall, 343 of the 570 contacted CCDDs completed the survey questionnaire (response rate: 60.2%). Nearly 4527 migrants were referred to these services in 2019. Migrants accounted for a median 1.1% (IQR: 0.9%-2.8%) of overall CCDD referrals. More than one-third of respondents reported that the number of migrants referred to their facilities had increased in the last 5 years. The overall quality of the migrants' cognitive assessment was deemed to be very poor or insufficient in most cases. A minority of CCDDs had translated information material on dementia and reported the possibility to contact cultural mediators and interpreters. CONCLUSIONS: A relevant number of migrants are being referred to Italian CCDDs that are still not adequately prepared to deliver diversity-sensitive care and support.

Translations and cultural adaptations of the Montreal Cognitive Assessment: a systematic and qualitative review.

This study provides a systematic review of linguistically and culturally adapted versions of the original Montreal Cognitive Assessment (MoCA) full version. Adapted versions were identified through a systematic review in 3 databases and on the MoCA website. Overall, 86 culturally different versions of MoCA are available: 74 versions on the MoCA website (25 of them have a corresponding paper concerning the translation process found with the systematic review) and 12 additional versions identified only with the search in biomedical databases. Culturally different adapted versions of the MoCA were unevenly distributed across different geographic areas. The quality of the process of cultural adaptation of MoCA differs considerably among different available versions as well as the number of items adapted in the various language versions. The potential availability of many culturally adapted and translated versions of the MoCA increases the chance of offering a linguistically and culturally sensitive screening for cognitive impairment to diverse populations; further studies are needed to identify if MoCA can be considered a truly cross-cultural fair test.

Comparison of Oxford Cognitive Screen and Montreal Cognitive Assessment feasibility in the stroke unit setting. A pilot study.

Background: : Cognitive status evaluation is not routine in the acute stroke setting and there is no consensus on which neuropsychological tool is more feasible and informative. The aim of this pilot study was to compare the feasibility and acceptability of two brief cognitive tests, the Montreal Cognitive Assessment (MoCA) and the Oxford Cognitive Screen (OCS), in acute stroke, with a focus on patients' experience, administration time, and the cognitive data obtained. Methods: : Patients with a diagnosis of ischemic or hemorrhagic stroke or of transient ischemic attack admitted to two stroke units were included. The sample consisted of 34 participants (mean age ±SD 71.1 ± 16.1 years, 25 males). Within five days of onset, patients were evaluated by means of the MoCA and OCS by a trained neuropsychologist. Results: Both tests were feasible in the stroke unit setting and had a high level of acceptability by patients. MoCA test was fully completed by 25 patients, OCS by 21 patients. The OCS administration time was longer than that of the MoCA. However, OCS was perceived less demanding than MoCA by patients. Twenty patients completed both the MoCA and the OCS entirely, and only 2 of them did not show any impairment in both tests. Seventeen patients showed at least an impaired domain on the OCS and 15 patients presented with a MoCA global score below cut-off for cognitive impairment. Conclusions: Our preliminary study did not show a superiority of the OCS over the widely used MoCA, and suggests the need for further validation in larger samples of stroke patients, exploring tests accuracy in detecting cognitive post-stroke impairment.

Dementia among migrants and ethnic minorities in Italy: rationale and study protocol of the ImmiDem project.

INTRODUCTION: Due to the ongoing demographic and epidemiological transitions, estimating the phenomenon of dementia in migrants and minority groups, exploring its characteristics and challenges and implementing dedicated healthcare policies, constitute emerging and urgent matters for Western countries. In the present paper we describe the rationale and design of the 'Dementia in immigrants and ethnic minorities living in Italy: clinical-epidemiological aspects and public health perspectives" (ImmiDem) project. METHODS AND ANALYSIS: Three main aims will be pursued by the ImmiDem project. First, a survey of all Italian dementia services will be conducted with dedicated questionnaires in order to estimate and describe the proportion and characteristics of migrants seeking help for cognitive disturbances. The different clinical approaches for diagnosing dementia and the challenges encountered in the assessment of cognitive functioning and in the provision of care in these groups of individuals will also be investigated. Second, record linkage procedures of data routinely collected in regional Health Information Systems will be conducted in order to identify and monitor migrant individuals with dementia living in the Lazio region. Third, tailored national and local care-coordination pathways and/or good practices dedicated to migrants affected by dementia and cognitive disorders will be identified and promoted. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Italian National Institute of Health (protocol 10749; 5 April 2018). The project was launched in November 2018 and will end in November 2021. The findings of the project will be disseminated through scientific peer-reviewed journals as well as to the public via the Dementia Observatory website (https://demenze.iss.it).

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

A semi-quantitative sport-specific assessment of recurrent traumatic brain injury: the TraQ questionnaire and its application in American football.

Chronic traumatic encephalopathy (CTE) is very frequent and studied among contact sport players, above all American Football. Now, the defined diagnosis is only post-mortem and, consequently, more detailed diagnostic in-vivo instruments are needed to facilitate diagnosis and to allow a follow up. This clinical questionnaire (Trauma Questionnaire-TraQ) has been designed to investigate in parallel the traumatic load and clinical and cognitive subjective symptoms. It evaluates 4 anamnestic fields (specific sport activity, all previous pathological events, clinical manifestations compatible with TBI (traumatic brain injury) or CTE and subjective perception of personal memory efficacy with PRMQ questionnaire). The aim of TraQ questionnaire is to allow a standardized follow-up of active players and to identify subclinical disturbances that may become warnings. A pilot comparative study with TraQ on 105 subjects (75 AF players and 30 comparable people without a history of contact-sports activity) revealed that AF players have an increased amount of severe head trauma, an amplified level of subjective aggressiveness, more olfactory deficits but also more speech subjective problems, previously never related with CTE. In view of the obtained results, the TraQ seems to be useful (1) to obtain a better quantification of the traumatic load; (2) to differentiate the risk of long-term neurological consequences, allowing better management of different athletes right from the pre-symptomatic phases; (3) to manage prevention strategies if regularly applied to periodic visits to sports fitness; and (4) to identify the predisposing factors for the development of CTE and other neurological consequences of TBI with follow-up studies.

Total small vessel disease burden and brain network efficiency in cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with hemorrhagic and nonhemorrhagic markers small vessel disease (SVD). A composite score to quantify the total burden of SVD on MRI specifically for CAA patients was recently developed. Brain network alterations related to individual MRI markers of SVD in CAA were demonstrated. OBJECTIVES: Considering diffusion based network measures sensitive to detect different relevant SVD-related brain injury, we investigated if increased overall SVD injury on MRI corresponds to worse global brain connectivity in CAA. METHODS: Seventy-three patients (79.5% male, mean age 70.58±8.22years) with a diagnosis CAA were considered. SVD markers in total MRI SVD score included: lobar cerebral microbleeds, cortical superficial siderosis (cSS), white matter hyperintensities (WMH) and centrum semiovale-enlarged perivascular spaces. Diffusion imaging based network reconstruction was made. The associations between total MRI SVD score and global network efficiency (GNE) were analyzed. RESULTS: A modest significant inverse correlation between total MRI SVD score and GNE existed (p=0.013; R2=0.07). GNE was related with the presence of cSS and moderate-severe WMHs. CONCLUSIONS: An increased burden of SVD neuroimaging markers corresponds to more reductions in global brain connectivity, implying a possible cumulative effect of overall SVD markers on disrupted physiology. GNE was related with some components of the score, specifically cSS and moderate-severe WMHs.

Next generation sequencing for systematic assessment of genetics of small-vessel disease and lacunar stroke.

BACKGROUND: The pathogenesis of cerebral small-vessel disease (SVD) is still incompletely understood, although evidence from family and twin studies supports the hypothesis that genetic factors may contribute to SVD pathogenesis. Identification of genetic susceptibility factors for SVD may improve our knowledge on SVD pathogenesis. SVE-LA (Small Vessel and Lacunar) project is a multicenter prospective Lombardia region study aimed at applying innovative genetic technologies and accurate patient phenotyping to discover the genetic basis of SVD. METHODS: A continuous series of subjects (aged 15-80 years) with a clinically and radiologically defined lacunar stroke referring to the participating Lombardia region stroke centers and an adequate number of age- and sex-matched controls are being included into the study. For each patient, clinical, demographic, instrumental, and familial data are collected applying standardized forms. After informed consent, a DNA sample for genetic analysis from patients and controls has been collected. The next generation sequencing (NGS) technology was applied to systematically screen patients for the most important genetic factors both monogenic and polygenic associated with SVD. The study includes also a centralized quantitative and qualitative analysis of neuroimaging studies. RESULTS: Between March 2011 and October 2013, 212 lacunar stroke patients and 78 controls have been collected. Mean age of cases was 65.8 ± 11.1 years and 67% were men. CONCLUSIONS: This is the first study applying systematically NGS technology on a wide series of lacunar stroke patients. A translational approach combining a systematic genetic screening with a detailed phenotyping may facilitate the discovery of genetic basis and improve our knowledge in the pathogenesis of SVD.

White matter microstructural damage in small vessel disease is associated with Montreal cognitive assessment but not with mini mental state examination performances: vascular mild cognitive impairment Tuscany study.

BACKGROUND AND PURPOSE: Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment. Diffusion tensor imaging is sensitive to white matter microstructural damage. We investigated if diffusion tensor imaging-derived indices are more strongly associated with performances on MoCA or on the widely used mini mental state examination in patients with mild cognitive impairment and small vessel disease. METHODS: Mild cognitive impairment patients with moderate/severe degrees of white matter hyperintensities on MRI were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy and median values of mean diffusivity and fractional anisotropy of the cerebral white matter were studied and correlated with cognitive tests performances. RESULTS: Seventy-six patients (mean age 75.1±6.8 years, mean years of education 8.0±4.3) were assessed. In univariate analyses, a significant association of both MoCA and mini mental state examination scores with age, education, cortical atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and fractional anisotropy were associated with MoCA. In partial correlation analyses, adjusting for all demographic and neuroimaging variables, both mean diffusivity and fractional anisotropy were associated only with MoCA (mean diffusivity: r= -0.275, P=0.023; fractional anisotropy: r=0.246, P=0.043). CONCLUSIONS: In patients with mild cognitive impairment and small vessel disease, diffusion tensor imaging-measured white matter microstructural damage is more related to MoCA than mini mental state examination performances. MoCA is suited for the cognitive screening of patients with small vessel disease.

Confirmatory factor analysis of the Neuropsychological Assessment Battery of the LADIS study: a longitudinal analysis.

Age-related white matter changes have been associated with cognitive functioning, even though their role is not fully understood. This work aimed to test a 3-factor model of the neuropsychological assessment battery and evaluate how the model fit the data longitudinally. Confirmatory factor analysis (CFA) was used to investigate the dimensions of a structured set of neuropsychological tests administered to a multicenter, international sample of independent older adults (LADIS study). Six hundred and thirty-eight older adults completed baseline neuropsychological, clinical, functional and motor assessments, which were repeated each year for a 3-year follow-up. CFA provided support for a 3-factor model. These factors involve the dimensions of executive functions, memory functions, and speed and motor control abilities. Performance decreased in most neuropsychological measures. Results showed that executive functioning, memory and speed of motor abilities are valid latent variables of neuropsychological performance among older adults, and that this structure is relatively consistent longitudinally, even though performance decreases with time.

Factors predicting the Montreal cognitive assessment (MoCA) applicability and performances in a stroke unit.

The evaluation of cognitive status is not routine in the acute stroke setting. We aimed to investigate feasibility, applicability, and performances of the Montreal cognitive assessment (MoCA) in acute stroke patients. Consecutive stroke patients (ischemic or hemorrhagic) admitted to one stroke unit were evaluated 5-9 days after stroke with MoCA (score range: 0-30; higher scores indicate better cognitive performance). Pre-morbid functional and cognitive status was assessed by a structured interview to caregivers. Neuroimaging data regarding index stroke and pre-existing lesions were collected. From December 2009 to December 2010, out of 207 patients with stroke, 137 (66%) were enrolled [mean age 69.2 ± 14.8 years; males 62%; mean National Institute of Health and Stroke Scale (NIHSS) score 5.9 ± 7.9]. The most common reason for non-enrolment was unfitting the time window inclusion criteria. MoCA was entirely applicable to 113/137 (82.5%) patients and the mean score was 17.8 ± 7.1. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR (95% CI) = 1.4 (1.2-1.7) for each point], left sided lesions [OR (95% CI) = 18.8 (2.3-155.2)], and worse pre-morbid functional status [OR (95% CI) = 0.7 (0.6-0.9) for each point of the instrumental activity of daily living scale]. Factors influencing MoCA performance were low education (ß = 0.264, p < 0.01), higher NIHSS scores (ß = -0.277, p < 0.01) and worse pre-morbid functional status (ß = 0.504, p < 0.001). MoCA administration is feasible in acute patients with mild-to-moderate stroke, with lesion location, stroke severity, and pre-morbid functional status as major determinants of its applicability and performance. MoCA seems to reveal some degree of cognitive deficit even in patients with mild stroke.

Low cerebrospinal fluid sulfatide predicts progression of white matter lesions: The LADIS study.

BACKGROUND/AIMS: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. METHODS: CSF from elderly individuals with WML was analyzed for amyloid markers, total τ, hyperphosphorylated τ, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). RESULTS: 37 subjects (age 73.6 ± 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). CONCLUSION: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.

The use of CT in dementia.

Neuroimaging has become part of the required investigations when assessing a patient with dementia. In this brief paper, we summarize the role of computed tomography (CT) in the routine work-up in dementia and provide some information about the role of the CT scan in the field of dementia research. Although CT is far less sensitive than magnetic resonance imaging (MRI) in detecting changes associated with cognitive impairment, it may still have a role in this regard. This role is mainly that of detecting secondary, sometimes treatable causes of cognitive impairment, such as intracranial masses. In this sense, CT should be seen as a first-line tool. Possible advantages of CT are lower cost; shorter acquisition time, making it more adaptable to patients with poor compliance; and the possibility that it can be performed in patients with metal devices, such as a pacemaker. The role of CT in the field of dementia research is very restricted in comparison to that of MRI, and is limited to the structural assessment of vascular lesions, and to a lesser extent, to that of degenerative changes, particularly when using specific slicing.

Comparison of the Alzheimer's Disease Assessment Scale Cognitive Subscale and the Vascular Dementia Assessment Scale in differentiating elderly individuals with different degrees of white matter changes. The LADIS Study.

BACKGROUND/AIMS: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) is a widely used rating instrument. The Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) includes additional tests reflecting mental speed and executive functions. The objective of this study was to compare the results of the two scales among subjects with various degrees of white matter hyperintensities (WMHs). METHODS: In the multicentre, multinational Leukoaraiosis and Disability in the Elderly (LADIS) study, 616 non-disabled subjects between the ages of 65 and 84 were examined using MRI, the ADAS-cog and VADAS-cog. The WMH rating from the MRI divided the patients into groups of mild (n = 280), moderate (n = 187) and severe (n = 149) degrees of change. RESULTS: Covariance analysis controlling for the effect of age and education revealed that the ADAS-cog differentiated only the mild and severe WMH groups, while the differences between all three groups were highly significant with the VADAS-cog. CONCLUSIONS: The VADAS-cog significantly differentiated between all the white matter groups. In comparison, the ADAS-cog differentiated only severe changes. Accordingly, the VADAS-cog may be a more sensitive endpoint in studies of patients with white matter load and vascular burden of the brain.