Validation in French of the Montreal Cognitive Assessment 5-Minute, a brief cognitive screening test for phone administration.

BACKGROUND: The prevalence of cognitive impairment and dementia is high and steadily increasing. Early detection of cognitive decline is crucial since some interventions can reduce the risk of progression to dementia. However, there is a lack of manageable scales for assessing cognitive functions outside specialized consultations. Recently, the MoCA-5min, a short version of the Montreal Cognitive assessment (MoCA), phone-administered, was validated for screening for vascular cognitive impairment. The aim of the present study was to validate the MoCA-5min in French in diverse clinical populations. METHODS: The Cantonese version of the MoCA-5min was adapted for French language. Healthy volunteers and patients with possible or established cognitive impairment (Alzheimer's disease or related disorders, Parkinson's disease, Huntington's disease, type-2 diabetes) participated in the study. The original MoCA and the MoCA-5min were administered, by phone, with a 30-day interval. Alternate forms were used to reduce learning effects. RESULTS: The scores of the original MoCA and MoCA-5min correlated significantly (Spearman rho=0.751, P<0.0001, 95% confidence interval 0.657 to 0.819). Internal consistency was good (Cronbach alpha=0.795). The area under the ROC curve was 0.870 and the optimal cut-off value for separating patients with and without cognitive impairment with the MoCA-5min was≤27 with 87.32% sensitivity and 76.09% specificity. Interrater and test-retest reliability were adequate. CONCLUSION: This study demonstrates that the French version of the MoCA-5min is a valid and reliable scale for detecting cognitive impairment in different clinical populations. It is administrable by phone and thus suitable for remote assessment as well as for large-scale screening and epidemiological studies.

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.

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 Pick's 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.

Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17.

Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22. These hereditary disorders are known collectively as frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17). Although the clinical features and associated regional variations in the neuronal loss observed in different FTDP-17 kindreds are diverse, the diagnostic lesions of FTDP-17 brains are tau-rich filaments in the cytoplasm of specific subpopulations of neurons and glial cells. The microtubule associated protein (tau) gene is located on chromosome 17q21-22. For these reasons, we investigated the possibility that PPND and other FTDP-17 syndromes might be caused by mutations in the tau gene. Two missense mutations in exon 10 of the tau gene that segregate with disease, Asn279(Lys) in the PPND kindred and Pro301(Leu) in four other FTDP-17 kindreds, were found. A third mutation was found in the intron adjacent to the 3' splice site of exon 10 in patients from another FTDP-17 family. Transcripts that contain exon 10 encode tau isoforms with four microtubule (MT)-binding repeats (4Rtau) as opposed to tau isoforms with three MT-binding repeats (3Rtau). The insoluble tau aggregates isolated from brains of patients with each mutation were analyzed by immunoblotting using tau-specific antibodies. For each of three mutations, abnormal tau with an apparent Mr of 64 and 69 was observed. The dephosphorylated material comigrated with tau isoforms containing exon 10 having four MT-binding repeats but not with 3Rtau. Thus, the brains of patients with both the missense mutations and the splice junction mutation contain aggregates of insoluble 4Rtau in filamentous inclusions, which may lead to neurodegeneration.

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 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.