MoCA News

Background

Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer’s disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are epigenetic “readers” that may distort normal gene expression and contribute to chronic disorders.

Objective

To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE).

Methods

The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized to apabetalone or placebo in the cognition sub-study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score≥26 (normal performance), MoCA score 25–22 (mild cognitive impairment), and MoCA score≤21 (dementia). Exposure to apabetalone was equivalent in the treatment groups in each MoCA-defined group.

Results

Apabetalone was associated with an increased total MoCA score in participants with baseline MoCA score of≤21 (p = 0.02). There was no significant difference in change from baseline in the treatment groups with higher MoCA scores. In the cognition study, more patients randomized to apabetalone discontinued study drug for adverse effects (11.3% versus 7.9%).

Conclusion

In this randomized controlled study, apabetalone was associated with improved cognition as measured by MoCA scores in those with baseline scores of 21 or less. BET protein inhibitors warrant further investigation for late life cognitive disorders.
Citation

Cummings, Jeffrey et al. ‘Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial’. 1 Jan. 2021 : 1 – 13.

Abstract:
Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment.

Title:
Hyposmia Is Associated with Reduced Cognitive Function in COVID-19: First Preliminary Results

Background:
Hyposmia is frequently reported as an initial symptom in coronavirus disease 2019 (COVID-19).

Objective:
As hyposmia accompanies cognitive impairment in several neurological disorders, we aimed to study whether hyposmia represents a clinical biomarker for both neurological involvement and cognitive impairment in mild COVID-19. We aimed to study whether olfactory dysfunction (OD) represents a clinical biomarker for both neurological involvement and cognitive impairment in mild COVID-19.

Methods:
Formal olfactory testing using the Sniffin’Sticks® Screening test, neuropsychological assessment using the Montreal Cognitive Assessment (MoCA), and detailed neurological examination were performed in 7 COVID-19 patients with mild disease course and no history of olfactory or cognitive impairment, and 7 controls matched for age, sex, and education. Controls were initially admitted to a dedicated COVID-19 screening ward but tested negative by real-time PCR.

Results:
The number of correctly identified odors was significantly lower in COVID-19 than in controls (6 ± 3, vs. 10 ± 1 p = 0.028, r = 0.58). Total MoCA score was significantly lower in COVID-19 patients than in controls (20 ± 5 vs. 26 ± 3, p = 0.042, r = 0.54). Cognitive performance indicated by MoCA was associated with number of correctly identified odors in COVID-19 patients and controls (COVID-19: p = 0.018, 95% CI = 9–19; controls: p = 0.18, r = 0.63, 95% CI = 13–18.5 r = 0.64).

Discussion/Conclusion:
OD is associated with cognitive impairment in controls and mild COVID 19.OD may represent a potentially useful clinical biomarker for subtle and even subclinical neurological involvement in severe acute respiratory distress syndrome coronavirus-2 infection.

Citation
Pirker-Kees A, Platho-Elwischger K, Hafner S, Redlich K, Baumgartner C. Hyposmia Is Associated with Reduced Cognitive Function in COVID-19: First Preliminary Results. Dement Geriatr Cogn Disord. 2021 Apr 14:1-6. doi: 10.1159/000515575. Epub ahead of print. PMID: 33853062.

Title:
Slow but evident recovery from neocortical dysfunction and cognitive impairment in a series of chronic COVID-19 patients

Background:
Cognitive impairment is a frequent complaint in coronavirus disease-19 (COVID-19) and can be related to cortical hypometabolism on 18F-FDG PET at the subacute stage. However, it is unclear if these changes are reversible.

Methods:
We prospectively assessed Montreal Cognitive Assessment (MoCA) and 18F-FDG PET scans in 8 COVID-19 patients at the subacute (as no longer infectious) and chronic stages (approximately six months after symptom onset). The expression of the previously established COVID-19-related covariance pattern was analyzed at both stages to examine the time course of post-COVID-19 cognitive impairment. For further validation, we also conducted a conventional group analysis.

Results:
Follow-up 18F-FDG PET revealed a significant reduction of initial frontoparietal and, to a lesser extent, temporal glucose hypometabolism that was accompanied by a significant improvement in cognition. The expression of the previously established COVID-19-related pattern was significantly lower at follow-up and correlated inversely with MoCA performance. However, both 18F-FDG PET and cognitive assessment suggest a residual impairment. Conclusions: Although a significant recovery of regional neuronal function and cognition can be clearly stated, residuals are still measurable in some patients six months after the manifestation of COVID-19. Given the current pandemic situation and tremendous uncertainty concerning the long-term effects of COVID-19, the present study provides novel insights of highest medical and socioeconomic relevance.

Citation:
Blazhenets G, Schröter N, Bormann T, Thurow J, Wagner D, Frings L, Weiller C, Meyer PT, Dressing A, Hosp JA. Slow but evident recovery from neocortical dysfunction and cognitive impairment in a series of chronic COVID-19 patients. J Nucl Med. 2021 Mar 31:jnumed.121.262128. doi: 10.2967/jnumed.121.262128. Epub ahead of print. PMID: 33789937.

Title:
Cannabis Use and Cognitive Impairment Among Male Adolescents A Case-control Study

Abstract:
Cannabis use by adolescents is a public health problem because it can cause cognitive impairment and educational deterioration. The objective of this study was to assess the prevalence and correlates of cognitive impairment among male adolescents with cannabis use in comparison with a control group. This is a case-control study that included 1682 adolescents who just finished their secondary school. A drug screen was made for all participants. Cognitive assessment using Montreal Cognitive Assessment (MoCA) scale was carried out for adolescents with positive urine screen for cannabis and a control group of adolescents with negative urine screen for drugs. The prevalence of cannabis use among adolescents was 2.14%. About one third of the cases started to use cannabis before the age of 15 years. Fifty-six percent used cannabis frequently (>4 times/wk). Adolescents with cannabis use were more likely to have cognitive impairment based on MoCA than controls (78% vs. 44%, P=0.004). Cases were more likely to have impairment in naming, abstraction, orientation, and total MoCA score than controls. Adolescents who started cannabis use early (below 15 y) had impairment in visuospatial/executive, attention, language, abstraction, delayed recall, and total MoCA score compared with those who started late (above 15 y). In addition, adolescents who use cannabis frequently had impairment in all cognitive domains except naming compared with those who used it occasionally. To conclude, the current study found that adolescents with cannabis use were more likely to have cognitive impairment than controls and this impairment was associated with age of onset and frequency of cannabis use.

Citation:
Bassiony, Medhat MBBCh, MSc, MD; Ammar, Haidy K. MBBCh, MSc; Khalil, Yomna MBBCh, MSc, MD Cannabis Use and Cognitive Impairment Among Male Adolescents, Addictive Disorders & Their Treatment: March 24, 2021 – Volume Publish Ahead of Print – Issue – doi: 10.1097/ADT.0000000000000257

Title:
Longitudinal changes in MoCA performances in patients with mild cognitive impairment and small vessel disease. Results from the VMCI-Tuscany Study

Objectives:
The Montreal Cognitive Assessment (MoCA) is a cognitive screening test largely employed in vascular cognitive impairment, but there are no data about MoCA longitudinal changes in patients with cerebral small vessel disease (SVD). We aimed to describe changes in MoCA performance in patients with mild cognitive impairment (MCI) and SVD during a 2-year follow-up, and to evaluate their association with transition to major neurocognitive disorder (NCD).

Materials and Methods:
Within the prospective observational VMCI-Tuscany Study, patients with MCI and SVD underwent a comprehensive clinical, neuropsychological, and functional evaluation at baseline, and after 1 and 2 years.

Results:
Among the 138 patients (mean age 74.4 ± 6.9 years; males: 57%) who completed the study follow-up, 44 (32%) received a major NCD diagnosis. Baseline MoCA scores (mean±SD) were lower in major NCD patients (20.5 ± 5) than in reverter/stable MCI (22.2 ± 4.3), and the difference approached the statistical threshold of significance (p=.051). The total cohort presented a decrease in MoCA score (mean±SD) of -1.3 ± 4.2 points (-2.6 ± 4.7 in major NCD patients, -0.7 ± 3.9 in reverter/stable MCI). A multivariate logistic model on the predictors of transition from MCI to major NCD, showed MoCA approaching the statistical significance (OR=1.09, 95% CI=1.00–1.19, p=.049).

Discussion:
In our sample of MCI patients with SVD, longitudinal changes in MoCA performances were consistent with an expected more pronounced deterioration in patients who received a diagnosis of major NCD. MoCA sensitivity to change and predictive utility need to be further explored in VCI studies based on larger samples and longer follow-up periods.

Title:
Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: A longitudinal prospective study nested to a population cohort.

Background and purpose:
Neurological complications of SARS-CoV-2 infection are noticed among critically ill patients soon after disease onset. Information on delayed neurological sequelae of SARS-CoV-2 infection is nil. Following a longitudinal study design, the occurrence of cognitive decline among individuals with a history of mild symptomatic SARS-CoV-2 infection was assessed.

Methods:
Stroke- and seizure-free Atahualpa residents aged ≥40 years, who had pre-pandemic cognitive assessments as well as normal brain magnetic resonance imaging and electroencephalogram recordings, underwent repeated evaluations 6 months after a SARS-CoV-2 outbreak infection in Atahualpa. Patients requiring oxygen therapy, hospitalization, and those who had initial neurological manifestations were excluded. Cognitive decline was defined as a reduction in the Montreal Cognitive Assessment (MoCA) score between the post-pandemic and pre-pandemic assessments that was ≥4 points greater than the reduction observed between two pre-pandemic MoCAs. The relationship between SARS-CoV-2 infection and cognitive decline was assessed by fitting logistic mixed models for longitudinal data as well as exposure-effect models.

Results:
Of 93 included individuals (mean age 62.6 ± 11 years), 52 (56%) had a history of mild symptomatic SARS-CoV-2 infection. Post-pandemic MoCA decay was worse in seropositive individuals. Cognitive decline was recognized in 11/52 (21%) seropositive and 1/41 (2%) seronegative individuals. In multivariate analyses, the odds for developing cognitive decline were 18.1 times higher among SARS-CoV-2 seropositive individuals (95% confidence interval 1.75-188; p = 0.015). Exposure-effect models confirmed this association (β = 0.24; 95% confidence interval 0.07-0.41; p = 0.006).

Conclusions:
This study provides evidence of cognitive decline among individuals with mild symptomatic SARS-CoV-2 infection. The pathogenesis of this complication remains unknown.

Citation:
Del Brutto OH, Wu S, Mera RM, Costa AF, Recalde BY, Issa NP. Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: A longitudinal prospective study nested to a population cohort. Eur J Neurol. 2021 Feb 11:10.1111/ene.14775. doi: 10.1111/ene.14775. Epub ahead of print. PMID: 33576150; PMCID: PMC8014083.

Title:
T‐MoCA: A valid phone screen for cognitive impairment in diverse community samples

Introduction:
There is an urgent need to validate telephone versions of widely used general cognitive measures, such as the Montreal Cognitive Assessment (T‐MoCA), for remote assessments.

Methods:
In the Einstein Aging Study, a diverse community cohort (n = 428; mean age = 78.1; 66% female; 54% non‐White), equivalence testing was used to examine concordance between the T‐MoCA and the corresponding in‐person MoCA assessment. Receiver operating characteristic analyses examined the diagnostic ability to discriminate between mild cognitive impairment and normal cognition. Conversion methods from T‐MoCA to the MoCA are presented.

Results:
Education, race/ethnicity, gender, age, self‐reported cognitive concerns, and telephone administration difficulties were associated with both modes of administration; however, when examining the difference between modalities, these factors were not significant. Sensitivity and specificity for the T‐MoCA (using Youden’s index optimal cut) were 72% and 59%, respectively.

Discussion:
The T‐MoCA demonstrated sufficient psychometric properties to be useful for screening of MCI, especially when clinic visits are not feasible.

Citation:
Mindy J. Katz Cuiling Wang Caroline O. Nester Carol A. Derby Molly E. Zimmerman Richard B. Lipton Martin J. Sliwinski Laura A. Rabin First published: 05 February 2021 https://doi.org/10.1002/dad2.12144

Title:
COVID-19 severity impacts on long-term neurological manifestation after hospitalisation

Background:
Preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection and for long term sequalae including neurological manifestations

Methods:
A sample of 208 previously hospitalized COVID-19 patients, 165 patients were re-assessed at 6 months according to a structured standardized clinical protocol. Premorbid comorbidities and clinical status, severity of COVID-19 disease, complications during and after hospitalization were recorded.

Results:
At 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of neurological symptoms, being fatigue (34%), memory/attention (31%), and sleep disorders (30%) the most frequent. Subjects reporting neurological symptoms were affected by more severe respiratory SARS-CoV-2 infection parameters during hospitalisation. At neurological examination, 37.4% of patients exhibited neurological abnormalities, being cognitive deficits (17.5%), hyposmia (15.7%) and postural tremor (13.8%) the most common. Patients with cognitive deficits at follow-up were comparable for age, sex and pre-admission comorbidities but experienced worse respiratory SARS-CoV-2 infection disease and longer hospitalization.

Conclusions:
Long-term neurological manifestations after hospitalization due to COVID-19 infection affect one-third of survivors. Multiple neurological abnormalities including mild cognitive impairment are associated with the severity of respiratory SARS-CoV-2 infection.

Citation:
Andrea Pilotto, Viviana Cristillo, Stefano Cotti Piccinelli, Nicola Zoppi, Giulio Bonzi, Davide Sattin, Silvia Schiavolin, Alberto Raggi, Antonio Canale, Stefano Gipponi, Ilenia Libri, Martina Frigerio, Michela Bezzi, Matilde Leonardi, Alessandro Padovani
medRxiv 2020.12.27.20248903; doi: https://doi.org/10.1101/2020.12.27.20248903

Title:
Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

Background:
The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.

Methods:
Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments.

Findings:
At 2–3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044).

Interpretation:
A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness.

Citation:
Betty Raman, Mark Philip Cassar, Elizabeth M. Tunnicliffe, Nicola Filippini, Ludovica Griffanti, Fidel Alfaro-Almagro, et al.
Published: January 07, 2021 DOI: https://doi.org/10.1016/j.eclinm.2020.100683

Title:
Utility of a Screening Test (MoCa) to Predict Amyloid Physiopathology in Mild Cognitive Impairment

Introduction:
The MoCa (Montreal Cognitive Assessment) Screening test has become relevant in recent years in the screening of patients with Mild Cognitive Impairment (MCI). It is important to seek and study simple and reliable tools in clinical practices that correlate with biological markers that have been used to predict conversion from MCI to AD.

Objective:
To analyze the MOCA and its cognitive sub-scores and the relationship with Amyloid pathophysiology in Alzheimer’s Disease.

Methodology:
32 patients with MCI were studied, they were separated according positive (n: 20) and negative (n: 12) underlying amyloid pathology. The patients performed a extensive cognitive assessment that included MoCa Test.

Results:
MoCa Total Scores showed significantly different results between groups (p <0.001) as well as the Memory Score (MoCa MIS), the Executive (MoCa EIS), the Attentional Score (MoCa AIS)) (p < 0.001) and the Orientation Score (MoCa OIS)) (p < 0.05) with worse performance of patients with amyloid pathophysiology. Score of MoCa a cut-off point of < 24 was established, since the diagnostic sensitivity at this point was 83% and the specificity 70%.

Conclusions:
The MoCa is a useful tool to differentiate biomarker status in MCI. Future studies should study this tool in the prodromal phases of the disease.

Citation:
Adela Fendrych Mazancova, Evžen Růžička, Robert Jech, Ondrej Bezdicek, Test the Best: Classification Accuracies of Four Cognitive Rating Scales for Parkinson’s Disease Mild Cognitive Impairment, Archives of Clinical Neuropsychology, Volume 35, Issue 7, October 2020, Pages 1069–1077, https://doi.org/10.1093/arclin/acaa039

“It is important to note that no significant differences in global cognition evaluated by the MMSE were observed between prefrail and non-frail groups in the present study. However, cognitive differences between the groups were sensitively captured by using the MoCA. This finding suggests that there may be cognitive performance problems related to frailty that are not detectable by the global measurement of the MMSE alone. In this sense, efforts to detect and further understand frailty should include a consistent measurement of specific cognitive domains employing comprehensive neuropsychological testing.”

Title:
Test the Best: Classification Accuracies of Four Cognitive Rating Scales for Parkinson’s Disease Mild Cognitive Impairment.

Objective:
A progressive cognitive impairment is one of the frequent non-motor symptoms during Parkinson’s disease (PD) course. A short and valid screening tool is needed to detect an incipient cognitive deficit at the mild cognitive impairment stage in Parkinson’s disease (PD–MCI).

Method:
The present study aims to evaluate the classification accuracies of four cognitive screenings: Montreal Cognitive Assessment (MoCA), Mattis Dementia Rating Scale second edition (DRS–2), Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) in a cohort of PD patients (PD–MCI, n = 46; and Parkinson’s disease with normal cognition, PD-NC, n = 95) and Controls (n = 66). All subjects underwent a standard neuropsychological battery as recommended by the International Parkinson and Movement Disorder Society and underwent all four screening tools.

Results:
In the detection of PD-MCI versus PD-NC, the MoCA showed a sensitivity of 84% and a specificity of 66% with a screening cutoff score at ≤25 points. The MoCA’s AUC was 86% (95% CI 78.7–93.1). In the detection of PD-MCI versus Controls, the FAB displayed 84% sensitivity and 79% specificity with a cutoff ≤16 points, to screen. The FAB’s AUC was 87% (79.0–95.0).

Conclusions:
Our results show that the MoCA is the most discriminative tool for screening MCI in the PD population.

Citation:
Adela Fendrych Mazancova, Evžen Růžička, Robert Jech, Ondrej Bezdicek, Test the Best: Classification Accuracies of Four Cognitive Rating Scales for Parkinson’s Disease Mild Cognitive Impairment, Archives of Clinical Neuropsychology, Volume 35, Issue 7, October 2020, Pages 1069–1077, https://doi.org/10.1093/arclin/acaa039

Title:
Study names best-performing cognitive impairment screening test for patients on dialysis

Background:
Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management.

Methods:
From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment. Using area-under-the-curve (AUC) analysis, we then examined the predictive ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test, determining each test’s performance for identifying severe cognitive impairment.

Results:
Mean age was 64 years; 61% were men, 39% were black, and 94% had at least a high-school education. Of the 150 participants, 21% had normal cognitive function, 17% had mild cognitive impairment, 33% had moderate impairment, and 29% had severe impairment. The Montreal Cognitive Assessment had the highest overall predictive ability for severe cognitive impairment (AUC, 0.81); a score of ≤21 had a sensitivity of 86% and specificity of 55% for severe impairment, with a negative predictive value of 91%. The Trails B and Digit Symbol tests also performed reasonably well (AUCs, 0.73 and 0.78, respectively). The other tests had lower predictive performances.

Conclusions:
The Montreal Cognitive Assessment, a widely available and brief cognitive screening tool, showed high sensitivity and moderate specificity in detecting severe cognitive impairment in patients on maintenance hemodialysis.

Citation:
Drew DA, et al. J Am Soc Nephrol. 2020;
doi:10.1681/ASN.2019100988.

Title:
Prediction of cognitive progression in Parkinson’s disease using three cognitive screening measures

Introduction:
Cognitive impairment is a common complication of Parkinson’s disease (PD) and identifying risk factors for progression to Parkinson’s disease dementia (PDD) is important. However, little research has been done comparing the utility of commonly used cognitive screening tests in predicting cognitive progression in PD.

Methods:
We retrospectively reviewed data from patients with PD enrolled in the Pacific Udall Center who had baseline and longitudinal neuropsychological and global cognitive screening tests. The diagnostic accuracies of 3 common screening tests were compared: Montreal Cognitive Assessment (MoCA), Mattis Dementia Rating Scale (DRS-2), and Mini Mental Status Examination (MMSE). Cognitive diagnoses of PD with mild cognitive impairment (PD-MCI) and PDD were based on full neuropsychological testing and established Movement Disorder Society criteria. Logistic regression and Cox proportional hazards regression models were used to examine predictors of cognitive decline.

Results:
Four hundred seventy patients for whom scores on all 3 screening tests were available from the same assessment were included in a cross-sectional analysis. The MoCA demonstrated the best overall diagnostic accuracy for PD-MCI (AUC = 0.79, sensitivity = 76.4%) and for PDD (AUC = 0.89, sensitivity = 81.0%) compared to the DRS-2 and MMSE.

A longitudinal analysis was performed on the subset of patients (316/470; 67.2%) who were nondemented at baseline and had undergone two or more assessments. After controlling for covariates, the MoCA was the only test associated with progression to PDD (OR = 1.27 95% CI 1.1–1.5, p = 0.001) and faster time to dementia (HR = 1.3, 95% CI 1.1–1.4, p < 0.0001).

Conclusions:
This study provides additional support for the use of the MoCA as a primary screening tool for cognitive impairment in PD and is the first to show that the MoCA is a predictor of conversion to PDD.

Citation:
Hojoong M. Kim, Carter Nazor, Cyrus P. Zabetian, Joseph F. Quinn, Kathryn A. Chung, Amie L. Hiller, Shu-Ching Hu, James B. Leverenz, Thomas J. Montine, Karen L. Edwards, Brenna Cholerton, Prediction of cognitive progression in Parkinson’s disease using three cognitive screening measures, Clinical Parkinsonism & Related Disorders, Volume 1, 2019, Pages 91-97, ISSN 2590-1125,
https://doi.org/10.1016/j.prdoa.2019.08.006.

Title:
Cognitive screening instruments to identify vascular cognitive impairment: A systematic review

Introduction:
Vascular cognitive impairment (VCI) is common and important to detect as controlling risk factors, particularly hypertension, may slow onset and progression. There is no consensus as to which cognitive screening instrument (CSI) is most suitable for VCI. We systematically reviewed the psychometric properties of brief CSIs for vascular mild cognitive impairment (VMCI) and vascular dementia (VaD).

Methods:
Literature searches were performed using scholarly databases from inception until 31 May 2018. Studies were eligible if participants were aged 18 or older, interviewed face‐to‐face, and standard diagnostic criteria for VCI were applied, excluding those specifically identifying post‐stroke dementia. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.

Results:
Fifteen studies were identified including eight types of CSIs (27 subtests/variants) and 4575 participants (1015 with VCI), mean age range: 51.6 to 75.5 years. Most studies compared more than one instrument. Five papers examined clock‐drawing; four, the Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE); and three used the Brief Memory and Executive Test (BMET). The MoCA (AUC > 0.90) and MMSE (AUC: 0.86‐0.99) had excellent accuracy in differentiating VaD from controls; the MoCA had good internal consistency (Cronbach’s α: .83‐.88). The MoCA (AUC: 0.87‐0.93) and BMET (AUC: 0.94) had the greatest accuracy in separating VMCI from controls. Most studies had low to moderate risk of bias in all domains of the QUIPS. Data were heterogeneous, precluding a meta‐analysis.

Conclusions:
Although few studies were available and further research is required, data suggests that the MoCA is accurate and reliable for differentiating VaD and VMCI from controls.

Citation:
Mohd Zaquan Arif Abd Ghafar, Hayatul Nawwar Miptah, Rónán O’Caoimh
First published: 02 May 2019
https://doi.org/10.1002/gps.5136

Title:
Brief cognitive screening instruments for early detection of Alzheimer’s disease: a systematic review

Objectives:
The objective of this systematic review was (1) to give an overview of the available short screening instruments for the early detection of Alzheimer’s disease (AD) and (2) to review the psychometric properties of these instruments.

Methods:
First, a systematic search of titles and abstracts of PubMed and Web of Science was conducted between February and July 2015 and updated in April 2016 and May 2018. Only papers written in English or Dutch were considered. All full-text papers about cognitive screening instruments for the early detection of AD were included, resulting in the identification of 38 pencil and paper tests and 12 computer tests. In a second step, the psychometric quality of these instruments was evaluated. Therefore, the same databases were searched again to identify papers that described the psychometric properties of the instruments meanwhile applying diagnostic criteria for the diagnostic groups included.

Results:
Out of 1454 papers, 96 clearly discussed the psychometric properties of the instruments. Eighty-nine papers discussed pencil and paper tests of which 80 were validated in a memory clinic setting. Based on the number of studies (31 articles) and the sensitivity (84%) and specificity (74%) values, the Montreal Cognitive Assessment (MoCA) seems to be a promising (pencil and paper) screening test for memory clinic testing as well as for population screening. Regarding computer tests, validation studies were only available for 7 out of 12 tests.

Conclusions:
A large number of screening tests for AD are available. However, most tests are only validated in a memory clinic setting and description of the psychometric properties of the instruments is limited. Especially, computer tests require further research. The MoCA is a promising instrument, but the specificity to detect early AD is rather low.

Citation:
De Roeck et al. Alzheimer’s Research & Therapy (2019) 11:21 https://doi.org/10.1186/s13195-019-0474-3

Title:
Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke

Objective:
To examine whether the Montreal Cognitive Assessment (MoCA) administered within 7 days after stroke predicts long-term cognitive impairment, functional impairment, and mortality.

Methods:
MoCA was administered to 274 patients from 2 prospective hospital-based cohort studies in Germany (n = 125) and France (n = 149). Cognitive and functional outcomes were assessed at 6, 12, and 36 months after stroke by comprehensive neuropsychological testing, the Clinical Dementia Rating (CDR) scale, the modified Rankin Scale (mRS), and Instrumental Activities of Daily Living (IADL) and analyzed with generalized estimating equations. All-cause mortality was investigated by Cox proportional hazard models. Analyses were adjusted for demographic variables, education, vascular risk factors, premorbid cognitive status, and NIH Stroke Scale scores. The additive predictive value of MoCA was examined with receiver operating characteristic curves.

Results:
In pooled analyses, a baseline MoCA score 2 (OR 5.03, 95% CI 2.20–11.51) and by IADL score 2, 0.88 vs 0.84, p = 0.047).

Conclusion:
Early cognitive testing by MoCA predicts long-term cognitive outcome, functional outcome, and mortality after stroke. Our results support routine use of the MoCA in stroke patients.

Citation:
Vera Zietemann, Marios K. Georgakis, Thibaut Dondaine, Claudia Müller, Anne-Marie Mendyk, Anna Kopczak, Hilde Hénon, Stéphanie Bombois, Frank Arne Wollenweber, Régis Bordet, Martin Dichgans
Neurology Nov 2018, 91 (20) e1838-e1850; DOI: 10.1212/WNL.0000000000006506

Title:
Comparing the Electronic and Standard Versions of the Montreal Cognitive Assessment in an Outpatient Memory Disorders Clinic: A Validation Study

The Montreal Cognitive Assessment (MoCA) has become widely used as a brief test of cognitive function in patients with neurological disease. More convenient application of the MoCA might increase its use and enhance its utility. An electronic version of the MoCA has recently been developed. To establish validity of the electronic version (eMoCA), discrepancy scores, concordance correlation coefficients (CCC), and root mean squared differences (RMSD) were calculated between each administration method in a sample of 43 new adult patients presenting with primary memory complaints. The CCC was 0.84 and the RMSD was 2.27, with 76% of the sample having a difference score within 2 points. Overall, this study establishes adequate convergent validity between the MoCA and eMoCA among an adult population presenting with memory concerns.

Citation:
Jody-Lynn Berg, January Durant, Gabriel C. Léger, Jeffrey L. Cummings, Ziad Nasreddine, and Justin B. Millera.
J Alzheimers Dis. 2018; 62(1): 93–97.
Published online 2018 Feb 6. doi: 10.3233/JAD-170896

Title:
Performance of Screening Tests for Cognitive Impairment in Systemic Lupus Erythematosus

Objective:
There is a need for a cognitive function screening test that can be administered to patients with systemic lupus erythematosus (SLE) in clinic. The objectives of this study were to determine (1) prevalence of cognitive impairment (CI) in SLE by the Montreal Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), in relation to the Hopkins Verbal Learning Test–Revised (HVLT-R), and Perceived Deficits Questionnaire 5-Item (PDQ-5); and (2) associated factors with CI.

Methods:
Consecutive patients followed at a single center were recruited. HVLT-R, MoCA, and MMSE were administered. Sensitivity/specificity, positive (PPV)/negative (NPV) predictive values, and positive likelihood ratio (LR+) of MoCA/MMSE were determined (compared to HVLT-R). A test on intellectual ability and questionnaires on anxiety, depression, and perceived cognitive deficits were completed. Regression analyses determined associations with CI.

Results:
Of 98 patients, 48% had CI using MoCA and 31% using HVLT-R. Sensitivity was higher for MoCA (73%) compared to MMSE (27%), though MMSE was more specific (90%) than MoCA (63%). PPV and LR+ were similar in MoCA and MMSE (PPV: 47%, 53%; LR+: 2.0, 2.6, respectively), but NPV was higher in MoCA (84%) than MMSE (74%). PDQ-5 predicted objective CI (HVLT-R: sensitivity 100%, specificity 89%). Although CI was associated with depression in univariate analyses, it did not hold in the multivariate analysis, while longer SLE disease duration and more years of education remained significant.

Conclusion:
CI is highly prevalent and MoCA may be a useful tool to screen for CI in SLE. Patients with more years of education were less likely to have CI.

Citation:
Stephanie G. Nantes, Jiandong Su, Ashneet Dhaliwal, Kenneth Colosimo and Zahi Touma
The Journal of Rheumatology September 2017, jrheum.161125; DOI: https://doi.org/10.3899/jrheum.161125

Title:
Cognitive Tests to Detect Dementia A Systematic Review and Meta-analysis

Importance:
Dementia is a global public health problem. The Mini-Mental State Examination (MMSE) is a proprietary instrument for detecting dementia, but many other tests are also available.

Objective:
To evaluate the diagnostic performance of all cognitive tests for the detection of dementia.

Data Sources:
Literature searches were performed on the list of dementia screening tests in MEDLINE, EMBASE, and PsychoINFO from the earliest available dates stated in the individual databases until September 1, 2014. Because Google Scholar searches literature with a combined ranking algorithm on citation counts and keywords in each article, our literature search was extended to Google Scholar with individual test names and dementia screening as a supplementary search.

Study Selection:
Studies were eligible if participants were interviewed face to face with respective screening tests, and findings were compared with criterion standard diagnostic criteria for dementia. Bivariate random-effects models were used, and the area under the summary receiver-operating characteristic curve was used to present the overall performance.

Main Outcomes and Measures:
Sensitivity, specificity, and positive and negative likelihood ratios were the main outcomes.

Results:
Eleven screening tests were identified among 149 studies with more than 49 000 participants. Most studies used the MMSE (n = 102) and included 10 263 patients with dementia. The combined sensitivity and specificity for detection of dementia were 0.81 (95% CI, 0.78-0.84) and 0.89 (95% CI, 0.87-0.91), respectively. Among the other 10 tests, the Mini-Cog test and Addenbrooke’s Cognitive Examination–Revised (ACE-R) had the best diagnostic performances, which were comparable to that of the MMSE (Mini-Cog, 0.91 sensitivity and 0.86 specificity; ACE-R, 0.92 sensitivity and 0.89 specificity). Subgroup analysis revealed that only the Montreal Cognitive Assessment had comparable performance to the MMSE on detection of mild cognitive impairment with 0.89 sensitivity and 0.75 specificity.
Conclusions and Relevance
Besides the MMSE, there are many other tests with comparable diagnostic performance for detecting dementia. The Mini-Cog test and the ACE-R are the best alternative screening tests for dementia, and the Montreal Cognitive Assessment is the best alternative for mild cognitive impairment.

Citation:
Tsoi KKF, Chan JYC, Hirai HW, Wong SYS, Kwok TCY. Cognitive Tests to Detect Dementia: A Systematic Review and Meta-analysis. JAMA Intern Med. 2015;175(9):1450–1458. doi:10.1001/jamainternmed.2015.2152

Title:
Validation of the Montreal Cognitive Assessment Versus Mini-Mental State Examination Against Hypertension and Hypertensive Arteriopathy After Transient Ischemic Attack or Minor Stroke

Background and Purpose:
Lack of reduced cognitive impairment with blood pressure (BP) lowering in trials may reflect use of the Mini-Mental State Examination (MMSE), which is insensitive to mild cognitive impairment after cerebrovascular events compared with the Montreal Cognitive Assessment. We determined relationships between impairment on MMSE versus Montreal Cognitive Assessment (MoCA) with the major physiological determinant of vascular cognitive impairment: hypertension and hypertensive arteriopathy.

Methods:
Cognitive impairment in consecutive patients 6 months after transient ischemic attack or minor stroke was defined as significant, mild, or none (MMSE<23, 23–26, ≥27; MoCA<20, 20–24, ≥25) and related to 20 premorbid systolic BP readings, home BP measurement (3 measurements, 3×daily for 1 month), and hypertensive arteriopathy (creatinine, stroke versus transient ischemic attack, leukoaraiosis) by ordinal regression.

Results:
Of 463 patients, 45% versus 28% had at least mild cognitive impairment on the MoCA versus MMSE (P<0.001). Hypertensive arteriopathy was more strongly associated with cognitive impairment on the MoCA than MMSE (creatinine: odds ratio=3.99; 95% confidence interval, 2.06–7.73 versus 2.16, 1.08–4.33; event: 1.53, 1.06–2.19 versus 1.23, 0.81–1.85; leukoaraiosis: 2.09, 1.42–3.06 versus 1.34, 0.87–2.07). Premorbid and home BP measurement systolic BP were more strongly associated with impairment on vascular subdomains of the MoCA than MMSE (odds ratio/10 mm Hg: visuospatial 1.29 versus 1.05; attention 1.18 versus 1.07; language 1.22 versus 0.91; naming 1.07 versus 0.86).

Conclusions:
The stronger relationship between impairment on the MoCA with hypertensive arteriopathy, independent of age, indicates a greater sensitivity for vascular-origin cognitive impairment. Use of MoCA should improve sensitivity for cognitive impairment and treatment effects in future studies.

Citation:
Validation of the Montreal Cognitive Assessment Versus Mini-Mental State Examination Against Hypertension and Hypertensive Arteriopathy After Transient Ischemic Attack or Minor Stroke
Alastair J.S. Webb, DPhil, Sarah T. Pendlebury, DPhil, Linxin Li, DPhil, Michela Simoni, DPhil, Nicola Lovett, MRCP, Ziyah Mehta, DPhil, and Peter M. Rothwell, FMedSci

Title:
The MoCA: well-suited screen for cognitive impairment in Parkinson disease

Objective:
To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales for Outcomes in Parkinson disease-Cognition [SCOPA-COG]) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks.

Methods:
A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N).

Results:
Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve [AUC], 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value [NPV] 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval [CI] 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%).

Conclusions:
The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD. MoCA is well-suited screen for cognitive impairment in Parkinson disease.

Citation:
Dalrymple-Alford JC, MacAskill MR, Nakas CT, Livingston L, Graham C, Crucian GP, Melzer TR, Kirwan J, Keenan R, Wells S, Porter RJ, Watts R, Anderson TJ. The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology. 2010 Nov 9;75(19):1717-25. doi: 10.1212/WNL.0b013e3181fc29c9. PMID: 21060094.

Title:
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.

Citation:
Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria RN, Vinters HV, Holtzman DM, Rosenberg GA, Wallin A, Dichgans M, Marler JR, Leblanc GG. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006 Sep;37(9):2220-41. doi: 10.1161/01.STR.0000237236.88823.47. Epub 2006 Aug 17. Erratum in: Stroke. 2007 Mar;38(3):1118. Wallin, Anders [added]. PMID: 16917086.