Global Cortical Atrophy Is Associated with an Unfavorable Outcome in Stroke Patients on Oral Anticoagulation.

INTRODUCTION: Measures of cerebral small vessel disease (cSVD), such as white matter hyperintensities (WMH) and cerebral microbleeds (CMB), are associated with an unfavorable clinical course in stroke patients on oral anticoagulation (OAC) for atrial fibrillation (AF). Here, we investigated whether similar findings can be observed for global cortical atrophy (GCA). METHODS: Registry-based prospective observational study of 320 patients treated with OAC following AF stroke. Patients underwent magnetic resonance imaging (MRI) allowing assessment of GCA. Using the simplified visual Pasquier scale, the severity of GCA was categorized as follows: 0: no atrophy, 1: mild atrophy; 2: moderate atrophy, and 3: severe atrophy. Using adjusted logistic and Cox regression analysis, we investigated the association of GCA using a composite outcome measure, comprising: (i) recurrent acute ischemic stroke (IS); (ii) intracranial hemorrhage (ICH); and (iii) death. RESULTS: In our time to event analysis after adjusting for potential confounders (i.e., WMH, CMB, age, sex, diabetes, arterial hypertension, coronary heart disease, hyperlipidemia, and antiplatelet use), GCA was associated with an increased risk for the composite outcome in all three degrees of atrophy (grade 1: aHR 3.95, 95% CI 1.34-11.63, p = 0.013; grade 2: aHR 3.89, 95% CI 1.23-12.30, p = 0.021; grade 3: aHR 4.16, 95% CI 1.17-14.84, p = 0.028). CONCLUSION: GCA was associated with our composite outcome also after adjusting for other cSVD markers (i.e., CMB, WMH) and age, indicating that GCA may potentially serve as a prognostic marker for stroke patients with atrial fibrillation on oral anticoagulation.

Global cortical atrophy may be associated with fatigue in patients with parkinson's disease.

PURPOSE: Fatigue has been recognized as a common non-motor problem in patients with Parkinson's disease (PD). The determination of the clinical correlates of fatigue in PD patients is necessary. The purpose of this study was to explore the risk factors related to the severity of fatigue in PD. PATIENTS AND METHODS: In this study, 141 patients with PD were recruited. All patients were evaluated comprehensively, including motor function, fatigue severity scale (FSS), cognition and psychiatric status. Brain magnetic resonance imaging (MRI) examinations were performed to assess the severity of white matter hyperintensities, and the presence of silent lacunes, medial temporal lobe atrophy (MTLA), and global cortical atrophy (GCA). The crude associations of variables with FSS were examined using Pearson (nor-mally distributed) or Spearman correlation (categorical or non-normal distributed) analyses. Multiple linear regression analysis was performed to find the correlates of fatigue severity in PD patients. RESULTS: In the whole sample, with FSS as the dependent variable in a linear regression model, Hamilton Depression Rating Scale (HAM-D), GCA, female sex were significant correlates of FSS, accounting for 24% of the variance of it. When subjects with depression (HAM-D ≥ 35) were excluded, HAM-D, GCA, female sex remained significant correlates of FSS, accounting for 22% of the variance of FSS. There is no correlation between white matter hyperintensities and FSS. CONCLUSION: GCA may be an important correlate of the fatigue severity commonly observed in PD patients.

Neuropsychological and neuroimaging assessments of early cognitive impairment in patients after mild ischemic stroke and transient ischemic attack.

This study aimed to identify markers of early cognitive impairment after acute mild ischemic cerebrovascular disease. To further explore the relationship between neuroimaging markers of vascular and neurodegenerative injuries and post-stroke cognitive impairment, 86 patients with transient ischemic attack/acute mild ischemic stroke were recruited. Demographic information, clinical data, stroke scale scores (Modified Rankin Scale, National Institutes of Health Stroke Scale), and neuroimaging parameters (medial temporal lobe atrophy, global cortical atrophy, white matter hyperintensities, location and number of acute infarcts) were collected. All participants underwent neuropsychological evaluation at the time of discharge. The neurocognitive assessment was conducted using the Montreal Cognitive Assessment-Basic and Trail-Making Test A. It was found that low Montreal Cognitive Assessment-Basic scores were associated with global cortical atrophy and lower education levels. The completion time on the Trail-Making Test A was significantly correlated with medial temporal lobe atrophy and less education. It is concluded that global cortical atrophy and lower education levels can be used as rapid indicators of early cognitive impairment in patients after a transient ischemic attack and acute mild ischemic stroke. Medial temporal lobe atrophy also appears to be associated with mental processing speed in patients after a transient ischemic attack and acute mild ischemic stroke.

Differential Diagnosis of Behavioral Variant and Semantic Variant of Frontotemporal Dementia Using Visual Rating Scales.

BACKGROUND: Frontotemporal dementia (FTD) represents the second most frequent early onset of dementia in people younger than 65 years. The main syndromes encompassed by the term FTD are behavioral variant of Frontotemporal dementia (bvFTD), non-fluent variant primary progressive aphasia (nfvPPA) and semantic variant (SD). AIMS: To assess the bvFTD and SD, which represent the most common subtypes of FTD, using visual rating scales. METHODS: Brain MRI exams of 77 patients either with bvFTD (n=43) or SD (n=34) were evaluated. The rating scales used were: Global cortical atrophy (GCA), Fazekas Scale: periventricular (PV) and white matter (WM) changes, Koedam rating scale and visual scales regarding specific cortical regions: dorsofrontal (DF), orbitofrontal (OF), anterior cingulate (AC), basal ganglia (BG), anterior- temporal (AT), insula, lateral-temporal (LT), entorhinal (ERC), perirhinal (PRC), anterior fusiform( AF), anterior hippocampus (AHIP) and posterior hippocampus (PHIP). Both Left (L) and Right (R) hemispheres were evaluated. RESULTS: R-OF (p=0.059), L-OF (p<0.0005), L-AT (p=0.047) and L-AHIP (p=0.007) have a statistically significant effect on the variable occurrence of SD compared to bvFTD. The indicators with the highest value of the area under the curve (AUC) were R-AC (0.829), L-OF (0.808), L-AC (0.791) and L-AF (0.778). Highest sensitivity was achieved by R-OF (97%) and L-AF (75%). Highest specificity was achieved by L-OF (95%), L-AT (91%) followed by R-AC (84%). Best combination of sensitivity and specificity was achieved by L-AF (74%-79%), L-OF (56%-95%) and R-OF (97%-42%). Best combination of PPV and NPV was achieved by L-OF (90%-73%), LAT (83%-72%) and R-AC (77%-77%). CONCLUSION: Visual rating scales can be a practical diagnostic tool in the characterization of patterns of atrophy in FTLD and may be used as an alternative to highly technical methods of quantification.

Validation of an Magnetic Resonance Imaging Acquisition and Review Protocol for Alzheimer's Disease and Related Disorders.

PURPOSE: Magnetic resonance imaging (MRI) of the brain allows for the identification of structural lesions typical of Alzheimer's disease (AD), the main cause of dementia. However, to have a clinical impact, it is imperative that acquisition and reporting of this MRI-based evidence be standardized, ensuring the highest possible reliability and reproducibility. Our objective was to validate a systematic radiological MRI acquisition and review process in the context of AD. METHODS: We included 100 individuals with a suspicion of dementia due to AD for whom MRI were acquired using our proposed protocol of clinically achievable acquisitions and used a unified reading grid to gather semi-quantitative evidence guiding diagnostic. MRIs were read by 3 raters with different experience levels. Interrater reliability was measured using Cohen's kappa statistic. RESULTS: Interrater reliability average for lesions occupying space, hemorrhage, or ischemia, was respectively 0.754, 0.715, and 0.501. Average reliability of white matter hyperintensity burden (Fazekas), global cortical atrophy, and temporal lobe atrophy (Scheltens) scales was 0.687, 0.473, and 0.621 (right)/0.599 (left), respectively. The kappas for regional cortical atrophy (frontal, parietal, occipital, temporal, and posterior cingulum) varied from 0.281-0.678. The average MRI reading time varied between 1.43-5.22 minutes. CONCLUSIONS: The presence of space occupying lesions, hemorrhagic or ischemic phenomena, and radiological scales have a good interrater reproducibility in MRI. Coupled with standardized acquisitions, such a protocol should be used when evaluating possible dementias, especially those due to probable AD.

A new age-related cutoff of medial temporal atrophy scale on MRI improving the diagnostic accuracy of neurodegeneration due to Alzheimer's disease in a Chinese population.

BACKGROUND: Visual rating scales are still the most popular tools in assessing atrophy degrees of whole brain and lobes. However, the false negative rate of the previous cutoff score of visual rating scales was relatively high for detecting dementia of Alzheimer's type (DAT). This study aimed to evaluate the diagnostic value of new cutoffs of visual rating scales on magnetic resonance imaging for discriminating DAT in a Chinese population. METHODS: Out of 585 enrolled subjects, 296 participants were included and diagnosed as normal cognition (NC)(n = 87), 138 diagnosed as amnestic mild cognitive impairment (aMCI), and 71 as dementia of Alzheimer's type (DAT). Receiver operating characteristic (ROC) curve analyses were used to calculate the diagnostic value of visual rating sales (including medial temporal atrophy (MTA), posterior atrophy rating scale (PA),global cortical atrophy scale (GCA) and medial temporal-lobe atrophy index (MTAi))for detecting NC from DAT . RESULTS: Scores of MTA correlated to age and Mini-mental state examination score. When used to detect DAT from NC, the MTA showed highest diagnostic value than other scales, and when the cutoff score of 1.5 of MTA scale, it obtained an optimal sensitivity (84.5%) and specificity (79.1%) respectively, with a 15.5% of false negative rate. Cutoff scores and diagnostic values were calculated stratified by age. For the age ranges 50-64, 65-74, 75-84 years, the following cut-offs of MTA should be used, ≥1.0(sensitivity and specificity were 92.3 and 68.4%), ≥1.5(sensitivity and specificity were 90.4 and 85.2%), ≥ 2.0(sensitivity and specificity were 70.8 and 82.3%) respectively. All of the scales showed relatively lower diagnostic values for discriminating aMCI from NC. CONCLUSIONS: The new age-based MTA cutoff showed better diagnostic accuracy for detecting DAT than previous standard, the list of practical cut-offs proposed here might be useful in clinical practice.

Neuroimaging signatures of frailty: A population-based study in community-dwelling older adults (the Atahualpa Project).

AIMS: Frailty is a geriatric state of physical vulnerability that might be associated with cognitive decline in the absence of a concurrent neurodegenerative disorder. This assumes that neuroimaging studies are normal, but such examinations have rarely been considered for a frailty work-up. The present study identifies neuroimaging signatures in older adults interviewed with the Edmonton Frail Scale (EFS). METHODS: Community-dwellers aged ≥60 years enrolled in the Atahualpa Project were invited to undergo brain magnetic resonance imaging. Using generalized regression models, we evaluated the association between frailty and diffuse cortical and subcortical brain damage, after adjusting for relevant confounders. Multivariate models estimated the interaction of age in the association between frailty and these neuroimaging signatures. RESULTS: Out of 298 participants (mean age 70 ± 8 years, 57% women), 151 (51%) had moderate-to-severe cortical atrophy and 74 (25%) had moderate-to-severe white matter hyperintensities of presumed vascular origin. Mean EFS scores were 5 ± 3 points, with 140 (47%) individuals classified as robust, 65 (22%) as pre-frail and 93 (31%) as frail. Multivariate models showed a significant association between cortical atrophy with the continuous (P = 0.002) and the categorized (P = 0.008) EFS score. The relationship between white matter hyperintensities and the EFS was marginal. According to interaction models, prefrail or frail individuals aged ≥67 years presented more prominent neuroimaging signatures of diffuse cortical or subcortical damage than their robust counterparts. CONCLUSIONS: Neuroimaging signatures of frailty are mainly related to age. This reinforces the importance of early frailty detection to reduce its catastrophic consequences. Geriatr Gerontol Int 2017; 17: 270-276.

The association between poor sleep quality and global cortical atrophy is related to age. Results from the Atahualpa Project.

Community-dwellers aged ≥60 years enrolled in the Atahualpa Project underwent brain MRI and were interviewed with the Pittsburgh Sleep Quality Index. Of 290 participants, 94 (32%) had poor sleep quality and 143 (49%) had global cortical atrophy (GCA). In a logistic regression model (adjusted for demographics, cardiovascular risk factor, severe edentulism, symptoms of depression, the MoCA score, and neuroimaging signatures of cerebrovascular damage), poor sleep quality was associated with GCA (p=0.004). A multivariate probability model showed that the probability of moderate-to-severe GCA significantly increased in individuals with poor sleep quality aged ≥67 years. This study provides evidence for an association between poor sleep quality and GCA in older adults and the important interaction of age in this association.

Contribution of white matter hyperintensities, medial temporal lobe atrophy and cortical atrophy on outcome, seven to twelve years after ECT in severely depressed geriatric patients.

BACKGROUND: Depression and cognitive decline are highly prevalent and often coexisting, however, the association between depression and dementia remains unclear. White matter hyperintensities (WMH), medial temporal lobe atrophy (MTA) and global cortical atrophy (GCA) are associated with depression, mild cognitive impairment and dementia; these structural abnormalities may therefore represent a common underlying mechanism of these diseases. We conducted a naturalistic prospective follow-up study in patients with severe geriatric depression who were formerly treated with ECT. The aim of the study was to investigate the effects of structural abnormalities in the brain on cognitive decline, dementia and survival. METHOD: Survival data of 76 patients was obtained. 39 (51.3%) of them also participated in the follow-up study. Cognitive decline was identified 7-12 years after ECT (median 8.0), using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A diagnosis of dementia was obtained from the family doctor of the patients. RESULTS: Forty-two out of the 76 (55.3%) of the patients died during follow-up. Twenty-four out of the remained 39 (65.1%) patients who participated in the follow-up study reported cognitive decline and 7 among the 39 patients (17.9%) were diagnosed with dementia. Depression with psychotic symptoms was significantly associated with absence of cognitive decline at follow-up (p=0.007). WMH was significantly associated with mortality (plog rank=0.048). Finally, we observed a trend in significance between the association of GCA and cognitive decline at follow-up (p=0.078), CONCLUSIONS: Depression with psychotic symptoms is a depression subtype that might not be associated with cognitive decline at follow-up. Moderate or severe WMH before ECT in our cohort of depressed patients was associated with higher mortality and GCA was possibly associated with cognitive decline at follow-up.

Global cortical atrophy (GCA) associates with worse performance in the Montreal Cognitive Assessment (MoCA). A population-based study in community-dwelling elders living in rural Ecuador.

BACKGROUND/OBJECTIVE: Increasing numbers of individuals with cognitive impairment are posing economic threads to the developing world. Proper assessment of this condition may be complicated by illiteracy and cross-cultural factors. We conducted a population-based study in elders living in rural Ecuador to evaluate whether the MoCA associated with structural brain damage in less-educated populations. METHODS: Atahualpa residents aged ≥60 years were identified during a door-to-door survey and invited to undergo MRI for grading GCA. Using a multivariate generalized linear model, we evaluated whether MoCA scores correlates with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. RESULTS: Out of 311 eligible persons, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 141 (59%) were women, 199 (83%) had primary school education, 175 (73%) had poor CVH status, 30 (12%) had symptoms of depression and 104 (43%) had edentulism. Average MoCA scores were 18.5±4.7 points. GCA was mild in 108, moderate in 95, and severe in 26 persons. Total and most domain-specific MoCA scores were significantly worse in persons with moderate to severe GCA. In the multivariate model, mean MoCA score was associated with GCA severity (ß=2.38, SE=1.07, p=0.027). CONCLUSIONS: MoCA scores associate with severity of GCA after adjusting for potential confounders, and may be used as reliable estimates of structural brain damage. However, a lower cut-off than that recommended for developed countries, would be better for recognizing cognitive impairment in less educated populations.

The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community: A population-based and nested case-control study in rural Ecuador (The Atahualpa Project) / O teste cognitivo Leganés tem baixa correlação com atrofia cortical global avaliada por RM em uma comunidade socialmente desprovida. Um estudo de base populacional e caso-controle no Equador Rural (Projeto Atahualpa)

We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. Methods: Atahualpa residents aged greater 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (? 22 points) and in matched controls without dementia. Results: Out of 311 eligible subjects, 241(78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVHstatus, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored ? 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (?=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8/23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar?s test). Conclusion: The LCT does not correlate with severity ofGCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage.

O teste cognitivo Leganés (TCL) é um instrumento para o rastreio rápido de demência em idosos com baixo nível educacional. Objetivo: Tivemos como objetivo avaliar se o TCL associa-se com medidas de atrofia cortical global (ACG) e pode ser usado como um substituto para a lesão cerebral estrutural. Métodos: Residentes de Atahualpa com idade maior ou igual 60 anos identificados durante um levantamento porta-a-porta foram submetidos a ressonância magnética para avaliar a intensidade da ACG. Usando modelos lineares generalizados multivariados, avaliamos se escores TCL contínuos correlacionavam com a intensidade da ACG após ajustes para a dados demográficos, educação, saúde cardiovascular (CVH), depressão e edentulismo. Em um estudo caso-controle aninhado, avaliamos a gravidade da ACG em pessoas com escores no TCL abaixo do nível de corte para demência (? 22 pontos) e em pessoas pareados sem demência. Resultados: Dentre as 311 pessoas elegíveis, 241 (78%) foram selecionadas. A média de idade foi de 69,2±7,5 anos, 59% eram mulheres,83% tinham o ensino primário, 73% tinham mau estado CVH, 12% apresentaram sintomas de depressão e 43% tinham edentulismo. Pontuações médias no TCL foram 26,7±3 e 23 (9,5%) pessoas tinham 22 pontos. ACG foi leve em 108, moderada em 95 e grave em 26 pessoas. No modelo multivariado, a média de pontuação no TCL não foi associada com a gravidade da ACG (B=0,06, SE=0,34, p=0,853). ACG grave foi observada em 6 de 23 pacientes e em 8 de 23 controles (OR:0,67; IC 95%: 0,14-2,81, p=0,752, teste de McNemar). Conclusão: O TCL não se associa com a gravidade da ACG após o ajuste para possíveis fatores de confusão e não deve ser usado como uma estimativa confiável de dano cerebral estrutural.

The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community: A population-based and nested case-control study in rural Ecuador (The Atahualpa Project).

OBJECTIVE: We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. METHODS: Atahualpa residents aged > 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (< 22 points) and in matched controls without dementia. RESULTS: Out of 311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVH status, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored < 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (ß=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar's test). CONCLUSION: The LCT does not correlate with severity of GCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage.

O teste cognitivo Leganés (TCL) é um instrumento para o rastreio rápido de demência em idosos com baixo nível educacional. OBJETIVO: Tivemos como objetivo avaliar se o TCL associa-se com medidas de atrofia cortical global (ACG) e pode ser usado como um substituto para a lesão cerebral estrutural. MÉTODOS: Residentes de Atahualpa com idade > 60 anos identificados durante um levantamento porta-a-porta foram submetidos a ressonância magnética para avaliar a intensidade da ACG. Usando modelos lineares generalizados multivariados, avaliamos se escores TCL contínuos correlacionavam com a intensidade da ACG após ajustes para a dados demográficos, educação, saúde cardiovascular (CVH), depressão e edentulismo. Em um estudo caso-controle aninhado, avaliamos a gravidade da ACG em pessoas com escores no TCL abaixo do nível de corte para demência (< 22 pontos) e em pessoas pareados sem demência. RESULTADOS: Dentre as 311 pessoas elegíveis, 241 (78%) foram selecionadas. A média de idade foi de 69,2±7,5 anos, 59% eram mulheres, 83% tinham o ensino primário, 73% tinham mau estado CVH, 12% apresentaram sintomas de depressão e 43% tinham edentulismo. Pontuações médias no TCL foram 26,7±3 e 23 (9,5%) pessoas tinham < 22 pontos. ACG foi leve em 108, moderada em 95 e grave em 26 pessoas. No modelo multivariado, a média de pontuação no TCL não foi associada com a gravidade da ACG (ß=0,06, SE=0,34, p=0,853). ACG grave foi observada em 6 de 23 pacientes e em 8 de 23 controles (OR: 0,67; IC 95%: 0,14-2,81, p=0,752, teste de McNemar). CONCLUSÃO: O TCL não se associa com a gravidade da ACG após o ajuste para possíveis fatores de confusão e não deve ser usado como uma estimativa confiável de dano cerebral estrutural.