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INTRODUCTION: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic. METHODS: We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aß1-42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient's diagnosis and management. RESULTS: The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP. INTERPRETATION: Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico , Humanos , Fragmentos de Péptidos/líquido cefalorraquídeo , Estudios Retrospectivos , Atención Terciaria de Salud , Proteínas tau/líquido cefalorraquídeoRESUMEN
INTRODUCTION: It is well known that some patients with Alz-heimer's disease (AD) have atypical, nonamnestic presentations. While logopenic aphasia and posterior cortical atrophy are well-characterized atypical variants of AD, the behavioral/dysexecutive variant remains a controversial entity, lacking consensus regarding its distinctive clinical and imaging features. METHODS: We present a case series of 8 patients with biomarker confirmation of AD (cerebrospinal fluid [CSF] analysis or amyloid positron emission tomography [PET]) and a progressive frontal syndrome, defined as prominent behavioral and/or executive deficits at initial presentation. We characterize the cohort based on clinical features, cognitive performance in 4 domains (memory, visuospatial, executive, and language) as well as behavior on the Dépistage Cognitif de Québec (DCQ), and regional brain metabolism using 18F-fluorodeoxyglucose PET (FDG-PET). We compare these features with 8 age-matched patients diagnosed with the behavioral variant of frontotemporal dementia (bvFTD) and 37 patients with typical amnestic AD. RESULTS: Patients with the behavioral/dysexecutive variant of AD presented with early-onset (mean age: 59 years old) progressive executive and behavioral problems reminiscent of bvFTD, including disinhibition, loss of social conventions, and hyperorality. Patients scored higher on the Memory Index and lower on the Behavioral Index than patients with amnestic AD on the DCQ, yet they were indistinguishable from patients with bvFTD on each of the cognitive indices. Visual analysis of FDG-PET revealed half of patients with behavioral/dysexecutive AD presented with frontal hypometabolism suggestive of bvFTD and only 3/8 (37.5%) presented significant hypometabolism of the posterior cingulate cortex. Group-level analysis of FDG-PET data revealed that the most hypometabolic regions were the middle temporal, inferior temporal, and angular gyri in behavioral/dysexecutive AD and the inferior frontal gyrus, anterior cingulate cortex, caudate nucleus, and insula in bvFTD. CONCLUSION: The behavioral/dysexecutive variant of AD is a rare, atypical young-onset variant of AD defined clinically by early and prominent impairments in executive and behavioral domains. While behavioral/dysexecutive AD is hardly distinguishable from bvFTD using clinical and cognitive features alone, CSF biomarkers and temporoparietal hypometabolism help predict underlying pathology during life.
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Enfermedad de Alzheimer , Encéfalo , Tomografía de Emisión de Positrones/métodos , Edad de Inicio , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/psicología , Atrofia , Biomarcadores/análisis , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Canadá/epidemiología , Líquido Cefalorraquídeo/metabolismo , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
BACKGROUND/AIMS: The logopenic variant of primary progressive aphasia (lvPPA) is characterized by impaired word-finding and sentence repetition with phonologic errors but spared motor speech and grammar and semantic knowledge. Although its language deficits have been well studied, the full spectrum of cognitive changes in the lvPPA remains to be defined. We aimed to explore the neurocognitive profile of the lvPPA using a newly developed cognitive screening tool for atypical dementias, the Dépistage Cognitif de Québec (DCQ). METHODS: We compared 29 patients with lvPPA to 72 amnestic variant Alzheimer disease (aAD) to 438 healthy control (HC) participants. Performance on the 5 indexes of the DCQ (Memory, Visuospatial, Executive, Language and Behavioral) was compared between the 3 groups. RESULTS: Results showed a significantly lower performance for lvPPA participants in all neurocognitive domains, when compared to HC. When compared to aAD, lvPPA participants had significantly lower scores for language, executive, and visuospatial abilities, but not for memory and behavior. CONCLUSION: Altogether, these findings better define the neurocognitive changes of lvPPA.
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Envejecimiento/psicología , Enfermedad de Alzheimer , Afasia Progresiva Primaria , Pruebas del Lenguaje , Pruebas Neuropsicológicas , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Afasia Progresiva Primaria/diagnóstico , Afasia Progresiva Primaria/epidemiología , Afasia Progresiva Primaria/psicología , Cognición , Femenino , Evaluación Geriátrica/métodos , Humanos , Masculino , Quebec/epidemiologíaRESUMEN
INTRODUCTION: Early recognition of atypical dementia remains challenging partly because of lack of cognitive screening instruments precisely tailored for this purpose. METHODS: We assessed the validity and reliability of the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a newly developed cognitive screening test, to detect atypical dementia using a multicenter cohort of 628 participants. Sensitivity and specificity were compared to the Montreal Cognitive Assessment (MoCA). A predictive diagnostic algorithm for atypical dementia was determined using classification tree analysis. RESULTS: The DCQ showed excellent psychometric properties. It was significantly more accurate than the MoCA to detect atypical dementia. All correlations between DCQ indexes and standard neuropsychological measures were significant. A statistical model distinguished typical from atypical dementia with a predictive power of 79%. DISCUSSION: The DCQ is a better tool to detect atypical dementia than standard cognitive screening tests. Expanding the clinician's tool kit with the DCQ could reduce missed/delayed identification of atypical dementia and accelerate therapeutic intervention.
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Demencia , Errores Diagnósticos/prevención & control , Pruebas de Estado Mental y Demencia , Anciano , Estudios de Cohortes , Demencia/diagnóstico , Demencia/psicología , Diagnóstico Precoz , Femenino , Evaluación Geriátrica/métodos , Humanos , Masculino , Pruebas Neuropsicológicas , Quebec , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The Mini-Mental State Examination continues to be used frequently to screen for cognitive impairment in older adults, but it remains unclear how to interpret changes in its score over time to distinguish age-associated cognitive decline from an early degenerative process. We aimed to generate cognitive charts for use in clinical practice for longitudinal evaluation of age-associated cognitive decline. METHODS: We used data from the Canadian Study of Health and Aging from 7569 participants aged 65 years or older who completed a Mini-Mental State Examination at baseline, and at 5 and 10 years later to develop a linear regression model for the Mini-Mental State Examination score as a function of age and education. Based on this model, we generated cognitive charts designed to optimize accuracy for distinguishing participants with dementia from healthy controls. We validated our model using a separate data set of 6501 participants from the National Alzheimer's Coordinating Center's Uniform Data Set. RESULTS: For baseline measurement, the cognitive charts had a sensitivity of 80% (95% confidence interval [CI] 75% to 84%) and a specificity of 89% (95% CI 88% to 90%) for distinguishing healthy controls from participants with dementia. Similar sensitivities and specificities were observed for a decline over time greater than 1 percentile zone from the first measurement. Results in the validation sample were comparable, albeit with lower sensitivities. Negative predictive value was 99%. INTERPRETATION: Our innovative model, which factors in age and education, showed validity and diagnostic accuracy for determining whether older patients show abnormal performance on serial Mini-Mental State Examination measurements. Similar to growth curves used in pediatrics, cognitive charts allow longitudinal cognitive evaluation and enable prompt initiation of investigation and treatment when appropriate.
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Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Evaluación Geriátrica/métodos , Escala del Estado Mental/normas , Anciano , Anciano de 80 o más Años , Canadá , Cognición , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Memoria a Corto Plazo , Pruebas Neuropsicológicas , PronósticoRESUMEN
OBJECTIVE: Amnestic mild cognitive impairment (aMCI) and late-life depression (LLD) both increase the risk of developing Alzheimer disease (AD). Very little is known about the similarities and differences between these syndromes. The present study addresses this issue by examining the nature of semantic memory impairment (more precisely, object-based knowledge) in patients at risk of developing AD. METHODS: Participants were 17 elderly patients with aMCI, 18 patients with aMCI plus depressive symptoms (aMCI/D+), 15 patients with LLD, and 29 healthy controls. All participants were aged 55 years or older and were administered a semantic battery designed to assess semantic knowledge for 16 biological and 16 man-made items. RESULTS: Overall performance of aMCI/D+ participants was significantly worse than the 3 other groups, and performance for questions assessing knowledge for biological items was poorer than for questions relating to man-made items. CONCLUSION: This study is the first to show that aMCI/D+ is associated with object-based semantic memory impairment. These results support the view that semantic deficits in aMCI are associated with concomitant depressive symptoms. However, depressive symptoms alone do not account exclusively for semantic impairment, since patients with LLD showed no semantic memory deficit.
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Amnesia/complicaciones , Amnesia/psicología , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/psicología , Depresión/complicaciones , Depresión/psicología , Semántica , Anciano , Enfermedad de Alzheimer , Productos Biológicos , Estudios de Casos y Controles , Femenino , Humanos , Enfermedades de Inicio Tardío/complicaciones , Enfermedades de Inicio Tardío/psicología , Masculino , Materiales Manufacturados , Memoria , Persona de Mediana Edad , SíndromeRESUMEN
Semantic deficits have been documented in the prodromal phase of Alzheimer's disease, but it is unclear whether these deficits are associated with non-cognitive manifestations. For instance, recent evidence indicates that cognitive deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated by concomitant depressive symptoms. The purposes of this study were to (i) investigate if semantic memory impairment in aMCI is modulated according to the presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii) compare semantic memory performance of aMCI and aMCI-D groups to that of patients with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26 healthy control participants were administered a semantic questionnaire assessing famous person knowledge. Results showed that performance of aMCI-D patients was impaired compared to the control and LLD groups. However, in the aMCI group performance was comparable to that of all other groups. Overall, these findings suggest that semantic deficits in aMCI are somewhat associated with the presence of concomitant depressive symptoms. However, depression alone cannot account solely for the semantic deficits since LLD patients showed no semantic memory impairment in this study. Future studies should aim at clarifying the association between depression and semantic deficits in older adults meeting aMCI criteria. (JINS, 2011, 17, 865-874).
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Amnesia/etiología , Disfunción Cognitiva/complicaciones , Depresión/complicaciones , Semántica , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Reconocimiento en Psicología , Índice de Severidad de la Enfermedad , Estadística como AsuntoRESUMEN
Cerebellar contribution to non-motor functions has been supported by several animal, human and functional neuroimaging studies. Which cognitive skills and to what extent the cerebrocerebellar loops contribute remain unclear, however. Among other reasons, this may be explained by the fact that authors have studied patients with extracerebellar lesions. The goal of this study was to explore the role of the cerebellum in cognition and affect in patients with autosomal recessive cerebellar ataxia type 1 (ARCA-1), a newly described inherited cerebellar disease characterised by middle-age onset of ataxia as well as pure, severe and diffuse cerebellar atrophy. To this end, the performance of 21 ARCA-1 patients was compared to that of 21 normal controls paired for age and education on a 3-h battery of attention, executive, visuospatial and memory skills. Results indicated similar IQ, naming and declarative memory abilities between groups. ARCA-1 patients showed significant deficits in attention (attention span, speed of information processing, sustained attention), verbal working memory and visuospatial/visuoconstructional skills (3-D drawings, copy of a complex figure). Functional brain imaging in a subset of patients showed diffuse severe cerebellar hypometabolism associated with a small area of right parietal hypometabolism. None of the patients presented a significant affective syndrome. Correlational analyses suggested that cognitive deficits could not be explained by the severity of motor deficits, duration of disease or mood. Altogether, this study confirms that pure cerebellar damage as seen in ARCA-1 is associated with significant cognitive impairments but not with psychiatric comorbidity. These deficits are correlated with an overall moderate impact on patient's autonomy. Our data favour an indirect participation of the dorsolateral prefrontal and posterior parietal cortical areas to the cerebrocerebellar circuit.
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Ataxia Cerebelosa/patología , Ataxia Cerebelosa/fisiopatología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Adulto , Ataxia Cerebelosa/complicaciones , Trastornos del Conocimiento/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , SíndromeRESUMEN
BACKGROUND: Hypometabolism of the posterior cingulate cortex (PCC) is an important diagnostic feature of late-onset, amnestic Alzheimer's disease (AD) measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, it is unclear whether PCC hypometabolism has diagnostic value in young-onset, non-amnestic variants of AD, which exhibit less pathology in the hippocampus and default mode network. OBJECTIVE: Evaluate the prevalence and diagnostic value of PCC hypometabolism in non-amnestic variants of AD. METHODS: We retrospectively identified 60 patients with young-onset, atypical dementia who have undergone a detailed clinical evaluation, FDG-PET, and an amyloid biomarker (amyloid-PET or cerebrospinal fluid analysis). We quantitatively analyzed regional hypometabolism in 70 regions of interest (ROI) using the MIMneuro® software. RESULTS: Based on a cut-off of z-score < -1.5 for significant PCC hypometabolism, the prevalence of PCC hypometabolism in non-amnestic variants of AD was 65% compared to 28% in clinical variants of frontotemporal dementia (FTD). The ROI with the maximal hypometabolism was the dominant middle temporal gyrus in the language variant of AD (mean z score -2.28), middle occipital gyrus in PCA (-3.24), middle temporal gyrus in frontal AD (-2.70), and angular gyrus in corticobasal syndrome due to AD (-2.31). The PCC was not among the 10 most discriminant regions between non-amnestic variants of AD versus clinical variants of FTD. CONCLUSION: We conclude that PCC hypometabolism is not a discriminant feature to distinguish non-amnestic variants of AD from clinical variants of FTD-and should be interpreted with caution in patients with young-onset, non-amnestic dementia.
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Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Tomografía de Emisión de Positrones/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: We aimed to validate the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical degenerative syndromes, in the oldest old. METHODS: The DCQ was developed by expert behavioural neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioural variant frontotemporal dementia. It targets five relevant cognitive domains: Memory, Visuospatial, Executive, Language, and Behaviour. Validation was performed using a prospective community-based sample consisting of 53 healthy French-speaking Canadian volunteers aged between 80 and 94 years old. Normative data were derived from participants with no history of cognitive difficulties and a Montreal Cognitive Assessment (MoCA) score ≥ 24. RESULTS: The mean DCQ total score (out of 100) was 84.65 (SD = 6.33). Pearson's correlation coefficient showed a moderate, but significant, correlation (r = 0.36, p < .01) with the MoCA. Normative data shown in percentiles were stratified by age and education for DCQ total score and for each of the five cognitive domains. CONCLUSIONS: This study suggests that the DCQ is a valid cognitive screening test in the oldest old. It is proposed that the DCQ can help early identification of atypical degenerative syndromes.
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BACKGROUND: Patients with cognitive impairment no dementia (CIND) are at an increased risk of progression to Alzheimer's disease (AD). Whether subtle impairments in functional or social abilities at the CIND stage can predict progression to AD is not yet fully determined. We evaluated whether impairments on the Disability Assessment for Dementia (DAD) and Functional Rating Scale (FRS) can predict progression to AD. METHODS: We examined 70 patients with CIND from the ACCORD cohort having complete DAD and FRS baseline and 2-year follow-up data. MANCOVA adjusted for age, sex, education and baseline MMSE score compared the baseline and 2-year change in DAD and FRS scores in CIND patients who progressed to AD versus non-progressors. RESULTS: There were no significant differences between CIND progressors and non-progressors in baseline total DAD or FRS scores. FRS domain analysis revealed that greater impairment in social/occupational functioning significantly predicted progression, while there were no predictive DAD domains. In progressors, both DAD and FRS scores significantly declined over time with the largest changes in instrumental activities of daily living (IADL). CONCLUSION: While changes in IADL characterize the progression from CIND to AD, impairment in complex social-cognitive competency significantly predicts risk of progression and may mark early AD.
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Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/fisiopatología , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/fisiopatología , Evaluación de la Discapacidad , Índice de Severidad de la Enfermedad , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Conducta SocialRESUMEN
OBJECTIVE: This study aimed to validate and provide normative data for the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical dementias. METHOD: The DCQ was developed by expert behavioral neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioral variant frontotemporal dementia. It targets five relevant domains: Memory, Visuospatial, Executive, Language, and Behavior. Validation was performed in a population-based sample of 410 healthy French-speaking Canadians aged between 50 and 89 years old. Normative data were derived from a subsample of 285 participants. RESULTS: Mean DCQ total score (out of 100) was 89.17 (SD = 7.36). Pearson's correlation coefficient showed a strong and significant correlation (r = .71, p < .001) with the Montreal Cognitive Assessment. Internal consistency for the cognitive domains assessed by Cronbach's alpha was satisfactory (.74). Test-retest reliability was adequate (Pearson's coefficient = . 70, p < .001) and interrater reliability, excellent (intraclass correlation = .99, p < .001). Normative data shown in percentiles were stratified by age and education. CONCLUSIONS: This study suggests that the DCQ is a valid and reliable cognitive screening test. Application of the DCQ on populations with atypical dementias is underway to derive sensitivity and specificity values for various dementias.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Demencia/diagnóstico , Demencia/psicología , Pruebas Neuropsicológicas , Psicometría/métodos , Psicometría/normas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Quebec , Reproducibilidad de los Resultados , TraduccionesRESUMEN
In the past two decades there has been a tremendous effort among clinicians and searchers to improve the diagnostic criteria of the dementias on the basis of the differential neurological and neuropsychological profiles. This was an obligatory requirement for clinical trials and the development of treatments. Over the years it became rapidly evident that the cohorts of patients in studies had some degree of heterogeneity, making it difficult to interpret the results of some studies, particularly in the vascular dementias and the mild cognitive impairment (MCI) group. For example, many sub-types of the vascular group were included in clinical trials, such as the cortical strokes, the lacunar states and the diffuse white matter disease cases, and some of the patients might have had also mixed pathology. In addition, the standard DSM IV criteria for dementia no longer represent our present knowledge of the clinical profile of some of the dementias such as vascular dementia (VaD) and fronto-temporal dementia where the memory impairment is not necessarily the first requirement. To improve the validity of clinical trials and eventually help developing more appropriate treatments, we revised the present diagnostic criteria and made recommendations for some changes in the context of the 2nd Canadian Conference on the Development of Antidementia Therapies, held in 2004 and reviewed in the light of the recent literature as of early 2006. It is expected that in the near future, these dementia criteria for clinical trials will have to be revised again in order to include specific subtypes of the dementias as well as biomarkers, structural and functional imaging.
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Demencia/clasificación , Demencia/diagnóstico , Errores Diagnósticos/prevención & control , Trastornos Cerebrovasculares/clasificación , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/fisiopatología , Demencia/fisiopatología , Demencia Vascular/diagnóstico , Demencia Vascular/fisiopatología , Diagnóstico Diferencial , Técnicas de Diagnóstico Neurológico/normas , Progresión de la Enfermedad , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/fisiopatología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/fisiopatología , Valor Predictivo de las PruebasRESUMEN
This article critically considers current diagnostic criteria for dementia and reports recommendations approved by at least 80% of experts attending the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD3). There was consensus that many of the features proposed as essential to a diagnosis of dementia in the 1980s no longer are relevant (for example, the requirements for memory impairment, electroencephalogram and cerebrospinal fluid studies, age-specific exclusions). In addition, other syndromes such as frontotemporal dementia have been recognized and need to inform new dementia criteria. It is also recognized that a diagnosis of depression need not exclude a dementia diagnosis. Other proposals, such as neuropathology should be considered as additional evidence and not as a gold standard or that some people with dementia have prolonged plateaus so that progressive decline need not be a criterion for Alzheimer's disease (AD), were more controversial and did not receive similar support. Given the evidence of the last three decades, there is merit in reconsidering the criteria by which dementia and AD are diagnosed.
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The finger-to-nose test is routinely performed during the clinical assessment of patients with cognitive impairments. Although widely known to screen for cerebellar dysfunction by unmasking appendicular ataxia, we have found that this test could also be interpreted from a cognitive perspective. We describe two typical signs observed at the finger-to-nose test in Alzheimer's disease (AD) patients: the "second finger syndrome" and the "distal pressure sign". By retrospectively reviewing the medical records 461 patients followed at our academic memory clinic, we found that these signs are commonplace in AD, but not in vascular dementia or subjective cognitive impairment.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Examen Neurológico/métodos , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Anciano , Anciano de 80 o más Años , Demencia Vascular/diagnóstico , Femenino , Humanos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Accumulating evidence points to the superiority of the MoCA over the MMSE as a cognitive screening tool. To facilitate the transition from the MMSE to the MoCA in clinical and research settings, authors have developed MMSE-MoCA conversion tables. However, it is unknown whether a conversion table generated from Alzheimer's disease (AD) patients would apply to patients with other dementia subtypes like vascular dementia or frontotemporal dementia. Furthermore, the reliability and accuracy of MMSE-MoCA conversion tables has not been properly evaluated. METHOD: We retrospectively examined the MMSE-MoCA relationship in a large multicenter sample gathered from 3 Memory Clinics in Quebec, Canada (1492 patients). We produced an MMSE-MoCA conversion table using the equi-percentile method with log-linear smoothing. We then cross-validated our conversion table with the ADNI dataset (1202 patients) and evaluated its accuracy for future predictions. RESULTS: The MMSE-MoCA conversion table is consistent with previously published tables and has an intra-class correlation of 0.633 with the ADNI sample. However, we found that the MMSE-MoCA relationship is significantly modified by diagnosis (P < .01), with dementia subtypes associated with a dysexecutive syndrome showing a trend towards higher MMSE than other dementia syndromes for a given MoCA score. The large width of 95% confidence interval (CI) for a new prediction suggests questionable reliability for clinical use. CONCLUSION: In this study, we validated a conversion table between MMSE and MoCA using a large multicenter sample. Our results suggest caution in interpreting the tables in heterogeneous clinical populations, as the MMSE-MoCA relationship may be different across dementia subtypes.
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Enfermedad de Alzheimer/diagnóstico , Trastornos del Conocimiento/diagnóstico , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Anciano , Enfermedad de Alzheimer/etiología , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features. METHODS: Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months. RESULTS: Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n=97), vascular dementia (n=101) and mixed neurodegenerative/vascular dementia (n=126). Any ischemic lesion on neuroimaging increased the odds (odds ratio=9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and institutionalization (hazard ratio for combined adverse events=6.08, p<0.001). CONCLUSIONS: Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however, are more strongly associated with clinical features than with radiographic ones.
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Trastornos del Conocimiento/clasificación , Trastornos del Conocimiento/diagnóstico por imagen , Demencia Vascular/clasificación , Demencia Vascular/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastornos del Conocimiento/fisiopatología , Estudios de Cohortes , Demencia Vascular/fisiopatología , Técnicas de Diagnóstico Neurológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Radiografía , Análisis de Supervivencia , Factores de TiempoRESUMEN
Few studies have explored the rate of cognitive decline and caregiver burden within the context of a specialized memory clinic. When this was done, the focus was largely on functional decline related to Alzheimer's disease (AD). Our goal was to compare the longitudinal decline of AD patients to those with Vascular Dementia (VaD) on Mini-Mental State Examination (MMSE). We further explored the differential impact on caregiver burden. We retrospectively studied 237 charts from patients seen at our Memory Clinic between 2006 and 2012. The data was collected over 17 years. Cohorts were formed by excluding conditions other than AD and VaD, and including patients who had been assessed at least twice with the MMSE (AD: n = 83; mean age: 67.7 yo; VaD: n = 32; mean age: 73.3yo). A small group of 36 caregivers was surveyed by phone to explore caregiver burden. Results indicated that the natural history of MMSE changes in AD patients differed significantly from that of patients with VaD (F = 10.41, p<0.0014), with AD patients showing more cognitive decline over time. Sadness, stress/anxiety, fatigue, and sleep disorders were reported as the main preoccupations by caregivers and its impact was rated as 'severe' in 50% of cases. Altogether, this study provides further insight into the natural history of cognitive decline in AD and VaD. Future studies should explore the progression of dementing disorders in larger cohorts using prospective methodological designs.
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Diagnosis of atypical/unclear dementia is often difficult and this delays treatment initiation. Several authors have shown that beyond standard dementia workup, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reduces the number of unclear diagnoses, leads to earlier treatment, and has a beneficial impact on families. However, it is not uncommon that the FDG-PET findings are equivocal in this setting. For those cases, a repeat FDG-PET may clarify the diagnosis and prevent treatment delay. We retrospectively assessed the clinical impact of a repeat FDG-PET in 59 patients with atypical/unclear dementia syndromes and inconclusive initial FDG-PET. Changes in primary diagnosis, diagnostic confidence, and management following the second FDG-PET were examined. Conducting a second FDG-PET reduced the number of unclear diagnoses from 80% to 34% , led to diagnostic change in 24% of cases, and treatment modification in 22% of patients. Overall, the clinical impact was higher when initial diagnostic confidence was low and the second FDG-PET repeated ≥12 months after the first one. In tertiary care memory clinic settings, when diagnostic incertitude persists despite extensive evaluation and an equivocal FDG-PET, repeating the FDG-PET 12 months later can greatly clarify the diagnosis and improve management.
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Encéfalo/diagnóstico por imagen , Demencia/diagnóstico por imagen , Demencia/diagnóstico , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Estudios RetrospectivosRESUMEN
Recent studies have supported a role for amyloid positron emission tomography (PET) imaging in distinguishing Alzheimer's disease (AD) pathology from other pathological protein accumulations leading to dementia. We investigated the clinical utility of amyloid PET in the differential diagnosis of atypical dementia cases and its impact on caregivers. Using the amyloid tracer 18F-NAV4694, we prospectively scanned 28 patients (mean age 59.3 y, s.d. 5.8; mean MMSE 21.4, s.d. 6.0) with an atypical dementia syndrome. Following a comprehensive diagnostic workup (i.e., history taking, neurological examination, blood tests, neuropsychological evaluation, MRI, and FDG-PET), no certain diagnosis could be arrived at. Amyloid PET was then conducted and classified as positive or negative. Attending physicians were asked to evaluate whether this result led to a change in diagnosis or altered management. They also reported their degree of confidence in the diagnosis. Caregivers were met after disclosure of amyloid PET results and completed a questionnaire/interview to assess the impact of the scan. Our cohort was evenly divided between positive (14/28) and negative (14/28) 18F-NAV4694 cases. Amyloid PET resulted in a diagnostic change in 9/28 cases (32.1%: 17.8% changed from AD to non-AD, 14.3% from non-AD to AD). There was a 44% increase in diagnostic confidence. Altered management occurred in 71.4% (20/28) of cases. Knowledge of amyloid status improved caregivers' outcomes in all domains (anxiety, depression, disease perception, future anticipation, and quality of life). This study suggests a useful additive role for amyloid PET in atypical cases with an unclear diagnosis beyond the extensive workup of a tertiary memory clinic. Amyloid PET increased diagnostic confidence and led to clinically significant alterations in management. The information gained from that test was well received by caregivers and encouraged spending quality time with their loved ones.