Ziad Nasreddine

The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment

Objectives: To develop a 10‐minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first‐line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.

Brief screening tool for mild cognitive impairment in older Japanese: Validation of the Japanese version of the Montreal Cognitive Assessment

Aim:  The Montreal Cognitive Assessment (MoCA), developed by Dr Nasreddine (Nasreddine et al. 2005), is a brief cognitive screening tool for detecting older people with mild cognitive impairment (MCI). We examined the reliability and validity of the Japanese version of the MoCA (MoCA‐J) in older Japanese subjects.

From genotype to phenotype: A clinical, pathological, and biochemical investigation of frontotemporal dementia and parkinsonism (FTDP‐17) caused by the P301L tau mutation

Frontotemporal dementia is a heterogeneous, often inherited disorder that typically presents with the insidious onset of behavioral and personality changes. Two genetic loci have been identified and mutations in tau have been causally implicated in a subset of families linked to one of these loci on chromosome 17q21‐22. In this study, linkage analysis was performed in a large pedigree, the MN family, suggesting chromosome 17q21‐22 linkage. Mutational analysis of the tau coding region identified a C‐to‐T change in exon 10 that resulted in the conversion of proline to a leucine (P301L) that segregated with frontotemporal dementia in this family. The clinical and pathological findings in the MN family emphasize the significant overlap between Picks disease, corticobasal degeneration, and frontotemporal dementia and challenge some of the current dogma surrounding this condition. Pathological studies of two brains from affected members of Family MN obtained at autopsy demonstrate numerous tau‐positive inclusions that were most prominent in the frontal lobes, anterior temporal lobes, and brainstem structures, as well as Pick‐like bodies and associated granulovacuolar degeneration. These Pick‐like bodies were observed in 1 patient with motor neuron disease. Because exon 10 is present only in tau mRNA coding for a protein with four microtubule binding repeats (4R), this mutation should selectively affect 4Rtau isoforms. Indeed, immunoblotting demonstrated that insoluble 4Rtau is selectively aggregated in both gray and white matter of affected individuals. Although there was significant pathological similarity between the 2 cases, the pattern of degenerative changes and tau‐positive inclusions was not identical, suggesting that other genetic or epigenetic factors can significantly modify the regional topology of neurodegeneration in this condition. Ann Neurol 1999;45:704–715

Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia.

Background: Mild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. Methods: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. Results: We identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended. Interpretation: Physicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.

Dementia and neurodevelopmental predisposition: Cognitive dysfunction in presymptomatic subjects precedes dementia by decades in frontotemporal dementia

Dementia is typically thought of as a disease caused by the process of aging. Few studies have addressed the premorbid neuropsychological alterations in subjects at risk for the disease–an issue of great importance for the understanding and treatment of degenerative dementias. We used knowledge of the mutation carrier status in a family with inherited dementia to address this issue more efficiently than is possible in the general population, or in cases of inherited dementia where the mutational basis is unknown. Standard neuropsychological tests were used to detect evidence of dysfunction in frontal executive systems in 10 presymptomatic subjects with known mutation carrier status in the highly penetrant condition, frontotemporal dementia and parkinsonism linked to chromosome 17. Presymptomatic carriers demonstrated cognitive dysfunction that was not present in 6 nonmutation‐carrying relatives. Strikingly, frontal– executive dysfunction was apparent in some of the youngest mutation carriers many decades prior to the predicted onset of dementia. Thus, this dysfunction may reflect the native cognitive capacities of affected subjects. These results suggest a potentially important neurodevelopmental component to a dementing condition that has been predominantly considered to be a disease of aging; accordingly, this issue warrants study in other families to assess the applicability of these findings.

Pain after thalamic stroke: Right diencephalic predominance and clinical features in 180 patients

Objective To assess whether the thalamic pain syndrome of Dejerine-Roussy is produced preferentially by right diencephalic lesions and to elucidate its clinical features. Background Several experimental paradigms suggest that the right hemisphere is specialized for monitoring somatic states, including mediating pain. However, clinical studies of pain laterality have been inconclusive, possibly due to pathophysiologic diversity among analyzed patients. We collected reports of central pain laterality in a single, well-demarcated disorder, the Dejerine-Roussy syndrome. Design/Methods Reports from English, French, and German literature were identified through Medline search and bibliography-guided retrieval. Inclusion criteria were (1) thalamic lesion documented by CT, MRI, or postmortem examination and (2) contralateral pain. Exclusion criteria were (1) tumoral/nonvascular etiology (to optimize anatomic localization), (2) symptoms consisting solely of evoked dysesthesia without spontaneous pain, or (3) sidedness of lesion not clearly indicated. Cases were analyzed for laterality as well as secondary anatomic and clinical variables. Results Literature search identified 274 cases. After exclusions, 180 remained. A total of 114 had a right-sided thalamic lesion, 66 left-sided (p < 0.001). Laterality predominance was greater among men than women. The frequency of other components of the Dejerine-Roussy syndrome—sensory impairment, hemiparesis, ataxia, and choreoathetosis—did not significantly differ between right and left groups. Pain onset was within the first week poststroke in 36%. Frequency of spontaneous pain was 14% after any thalamic stroke and 24% after geniculothalamic artery territory stroke. Conclusion Right-sided lesions predominate among reported cases of the thalamic pain syndrome. This preferential involvement of the nondominant thalamus in pain processing is supportive evidence of a nondominant hemisphere specialization in monitoring somatic states.OBJECTIVE To assess whether the thalamic pain syndrome of Dejerine-Roussy is produced preferentially by right diencephalic lesions and to elucidate its clinical features. BACKGROUND Several experimental paradigms suggest that the right hemisphere is specialized for monitoring somatic states, including mediating pain. However, clinical studies of pain laterality have been inconclusive, possibly due to pathophysiologic diversity among analyzed patients. We collected reports of central pain laterality in a single, well-demarcated disorder, the Déjerine-Roussy syndrome. DESIGN/METHODS Reports from English, French, and German literature were identified through Medline search and bibliography-guided retrieval. Inclusion criteria were (1) thalamic lesion documented by CT, MRI, or postmortem examination and (2) contralateral pain. Exclusion criteria were (1) tumoral/nonvascular etiology (to optimize anatomic localization), (2) symptoms consisting solely of evoked dysesthesia without spontaneous pain, or (3) sidedness of lesion not clearly indicated. Cases were analyzed for laterality as well as secondary anatomic and clinical variables. RESULTS Literature search identified 274 cases. After exclusions, 180 remained. A total of 114 had a right-sided thalamic lesion, 66 left-sided (p < 0.001). Laterality predominance was greater among men than women. The frequency of other components of the Dejerine-Roussy syndrome--sensory impairment, hemiparesis, ataxia, and choreoathetosis--did not significantly differ between right and left groups. Pain onset was within the first week poststroke in 36%. Frequency of spontaneous pain was 14% after any thalamic stroke and 24% after geniculothalamic artery territory stroke. CONCLUSION Right-sided lesions predominate among reported cases of the thalamic pain syndrome. This preferential involvement of the nondominant thalamus in pain processing is supportive evidence of a nondominant hemisphere specialization in monitoring somatic states.

Mild cognitive impairment and cognitive impairment, no dementia: Part A, concept and diagnosis

Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND) are controversial emerging terms that encompass the clinical state between elderly normal cognition and dementia. This article reviews recent work on the classification of MCI and CIND, their prognosis, and diagnostic approaches and presents evidence‐based recommendations approved at the meeting of the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD3) held in Montreal in March, 2006. New short tools such as the Montreal Cognitive Assessment are making it easier for family physicians to confidently attach the label of MCI.

Psychometrics of the Montreal Cognitive Assessment (MoCA) and its subscales: validation of the Taiwanese version of the MoCA and an item response theory analysis

BACKGROUND The Montreal Cognitive Assessment (MoCA) is an instrument for screening mild cognitive impairment (MCI). This study examined the psychometric properties and the validity of the Taiwan version of the MoCA (MoCA-T) in an elderly outpatient population. METHODS Participants completed the MoCA-T, Mini-Mental State Examination (MMSE), and the Chinese Version Verbal Learning Test. The diagnosis of Alzheimers disease (AD) was made based on the NINCDS-ADRDA criteria, and MCI was diagnosed through the criteria proposed by Petersen et al. (2001). RESULTS Data were collected from 207 participants (115 males/92 females, mean age: 77.3 ± 7.5 years). Ninety-eight participants were diagnosed with AD, 71 with MCI, and 38 were normal controls. The area under the receiver operator curves (AUC) for predicting AD was 0.98 (95% confidence interval [CI] = 0.97-1.00) for the MMSE, and 0.99 (95% CI = 0.98-1.00) for the MoCA-T. The AUC for predicting MCI was 0.81 (95% CI = 0.72-0.89) using the MMSE and 0.91 (95% CI = 0.86-1.00) using the MoCA-T. Using an optimal cut-off score of 23/24, the MoCA-T had a sensitivity of 92% and specificity of 78% for MCI. Item response theory analysis indicated that the level of information provided by each subtest of the MoCA-T was consistent. The frontal and language subscales provided higher discriminating power than the other subscales in the detection of MCI. CONCLUSION Compared to the MMSE, the MoCA-T provides better psychometric properties in the detection of MCI. The utility of the MoCA-T is optimal in mild to moderate cognitive dysfunction.

Montreal Cognitive Assessment (MoCA): Concept and Clinical Review

The Montreal Cognitive Assessment (MoCA) is a cognitive screening instrument developed to detect mild cognitive impairment (MCI). It is a simple 10 minute paper and pencil test that assesses multiple cognitive domains including memory, language, executive functions, visuospatial skills, calculation, abstraction, attention, concentration, and orientation. Its validity has been established to detect mild cognitive impairment in patients with Alzheimer’s disease and other pathologies in cognitively impaired subjects who scored in the normal range on the MMSE. MoCA’s sensitivity and specificity to detect subjects with MCI due to Alzheimer’s disease and distinguish them from healthy controls are excellent. MoCA is also sensitive to detect cognitive impairment in cerebrovascular disease and Parkinson’s disease, Huntington’s disease, brain tumors, systemic lupus erythematosus, substance use disorders, idiopathic rapid eye movement sleep behaviour disorder, obstructive sleep apnoea, risk of falling, rehabilitation outcome, and epilepsy. There are several features in MoCA’s design that likely explain its superior sensitivity for detecting MCI. The MoCA’s memory testing involves more words, fewer learning trials, and a longer delay before recall than the MMSE. Executive functions, higher-level language abilities, and complex visuospatial processing can also be mildly impaired in MCI participants of various etiologies and are assessed by the MoCA with more numerous and demanding tasks than the MMSE. MoCA was developed in a memory clinic setting and normed in a highly educated population. Norms in lesser educated, community based, multi-cultural samples will hopefully be available to help first line healthcare providers better assess subjects presenting with cognitive complaints. The MoCA is freely accessible for clinical and educational purposes (www.mocatest.org), and is available in 36 languages and dialects.

Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sampleAuthor Response

# {#article-title-2} Rossetti et al.1 reported a population-based study of scores on the Montreal Cognitive Assessment (MoCA) in Texas. Compared to our study2 in Montreal, the Caucasian group of normal controls in the Rossetti et al. study was considerably younger (52.9 vs 72.8 years) and had slightly lower mean MoCA scores (25.6 vs 26.9). In the other ethnic groups, they found substantial effects of age and education on their MoCA scores. Subjects in our study were excluded if they had subjective complaints …