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1.
Alzheimer Dis Assoc Disord ; 36(4): 359-361, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35867966

RESUMEN

Some patients with subjective cognitive decline (SCD) progress to neurocognitive disorders (NCD), whereas others remain stable; however, the neuropsychological determinants of this progression have not been identified. Our objective was to examine baseline neuropsychological indicators that could discriminate between stable SCD Versus progression toward an NCD. We retrospectively included patients consulting for SCD at a university medical center's memory center (Amiens, France) who had undergone 3 or more neuropsychological assessments. Among the 80 patients with SCD, 11 had progressed to an NCD. The combination of age, memory, and speed scores at the baseline assessment predicted the progression of SCD with a sensitivity of 91%, and a negative predictive value of 98%. The present results constitute a first step (pending prospective studies) toward helping physicians to identify cases of SCD at risk of progression and, in particular, identifying patients with SCD who will not progress by examining baseline neuropsychological indicators. ClinicalTrials.gov ID: NCT04880252.


Asunto(s)
Disfunción Cognitiva , Humanos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Progresión de la Enfermedad , Pruebas Neuropsicológicas , Estudios Prospectivos , Estudios Retrospectivos
2.
PLoS Med ; 15(9): e1002660, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30248105

RESUMEN

BACKGROUND: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. METHODS AND FINDINGS: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Nifedipino/análogos & derivados , Nootrópicos/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/psicología , Progresión de la Enfermedad , Método Doble Ciego , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/uso terapéutico , Resultado del Tratamiento
3.
Alzheimer Dis Assoc Disord ; 32(2): 89-93, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29261520

RESUMEN

The diagnostic accuracy of hexamethylpropyleneamine oxime (HMPAo) single-photon emission computed tomography (SPECT) in Alzheimer disease (AD) remains undetermined in a "real-life" clinical population. The objective was to determine the HMPAo SPECT hypoperfusion pattern in cognitively impaired patients with positive CSF AD biomarker and to evaluate its diagnostic accuracy. This study included 120 patients referred to a university memory clinic assessed using HMPAo SPECT, MRI, and CSF biomarkers. Three biomarker signatures suggestive of AD were analyzed (1, Aß1-42; 2, Aß1-42+t-tau and/or p-tau; 3, Aß1-42/p-tau). The clinical diagnoses were possible AD (n=29) or other causes of cognitive impairment (n=91). All CSF AD signatures were significantly (1, P=0.004; 2, P=0.017; 3, P=0.024) associated with the difference between inferior parietal perfusion and lateral dorsal frontal cortex perfusion. The hypoperfusion pattern discriminated between patients with positive CSF AD biomarkers and those with other cognitive impairments with a sensitivity of 67% to 71% and a specificity of 63% to 65% and a greatest negative predictive value (NPV) of 90%. Inferior parietal cortex hypoperfusion was the most sensitive and specific feature in AD patients diagnosed using clinical and CSF biomarker criteria. This hypoperfusion pattern was associated with an NPV of 90% and therefore discriminated sharply between AD and other cognitive disorders.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Biomarcadores/líquido cefalorraquídeo , Lóbulo Parietal/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Femenino , Francia , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos
4.
Alzheimer Dis Assoc Disord ; 30(2): 140-4, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26485496

RESUMEN

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.


Asunto(s)
Disfunción Cognitiva/diagnóstico , Función Ejecutiva/fisiología , Pruebas Neuropsicológicas , Anciano , Enfermedad de Alzheimer/diagnóstico , Femenino , Humanos , Masculino , Modelos Estadísticos , Pruebas Neuropsicológicas/normas , Pruebas Neuropsicológicas/estadística & datos numéricos , Reproducibilidad de los Resultados
5.
J Alzheimers Dis ; 51(3): 793-800, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26923012

RESUMEN

The aim of this study was to examine the relationship between cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) (Aß1-42, t-tau, and p-tau) and 18Fluorodeoxyglucose positron emission tomography (FDG-PET) hypometabolism in subjects from the Alzheimer's Disease Neuroimaging Initiative, and specifically to determine which index of neurodegeneration was most frequently affected. The secondary objective was to determine the most frequently hypometabolic region in patients with a CSF AD signature (abnormal Aß1-42 and abnormal p-tau). We included the 372 subjects (85 normal subjects, 212 patients with mild cognitive impairment, and 75 patients with AD) with a CSF biomarker dosage (Aß1-42, t-tau, and p-tau) and brain FDG-PET. The relationship between FDG-PET metabolism (in five regions of interest (ROI) known to be damaged in AD) and CSF t-tau and p-tau levels was studied as a function of CSF Aß1-42 status. FDG-PET hypometabolism and CSF t-tau and p-tau levels were correlated only in patients with an abnormal CSF Aß1-42 level (t-tau: R2 = 0.044, p = 0.001; p-tau: R2 = 0.02, p = 0.03). In the latter patients, CSF p-tau was the most frequently (p = 0.0001) abnormal neurodegeneration marker (p-tau: 92.8%; FDG-PET: 56.5%; CSF t-tau: 59.1%). Within the five ROI of FDG PET, the angular gyrus metabolism (R2 = 0.149; p = 0.0001) was selected as the most tightly associated with CSF AD signature. The relation between CSF markers of neurodegeneration (p-tau and t-tau) and brain hypometabolism (in FDG-PET) is conditioned by presence of amyloid abnormality. This finding supports the current physiopathological model of AD. P-tau is the most frequently impaired biomarker. Using FDG PET angular gyrus hypometabolism is the most sensitive to CSF-biomarker-defined AD.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/epidemiología , Biomarcadores/líquido cefalorraquídeo , Encéfalo/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/epidemiología , Bases de Datos Factuales , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Fosforilación , Tomografía de Emisión de Positrones , Radiofármacos
6.
J Clin Exp Neuropsychol ; 35(7): 728-44, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23930667

RESUMEN

We explored the value of a battery of socioemotional tasks for differentiating between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Patients with FTLD (n = 13) or AD (n = 13) and healthy controls (n = 26) underwent a neuropsychological assessment and the socioemotional battery (an empathy questionnaire, an emotion recognition task, and theory of mind tasks). Socioemotional processes were markedly impaired in FTLD but relatively unaffected in mild AD. The computed Socioemotional Index discriminated more accurately between FTLD from AD than behavioral and executive assessments did. Furthermore, impairments in socioemotional processes were correlated with indifference to others.


Asunto(s)
Enfermedad de Alzheimer/psicología , Emociones/fisiología , Degeneración Lobar Frontotemporal/psicología , Conducta Social , Anciano , Análisis de Varianza , Diagnóstico Diferencial , Empatía/fisiología , Función Ejecutiva/fisiología , Expresión Facial , Femenino , Humanos , Individualidad , Relaciones Interpersonales , Masculino , Memoria/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Curva ROC , Reconocimiento en Psicología/fisiología , Encuestas y Cuestionarios , Teoría de la Mente
7.
Arch Pathol Lab Med ; 128(5): 568-70, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15086300

RESUMEN

We report a case of gastric myeloid metaplasia in an 89- year-old woman with agnogenic myeloid metaplasia. The lesions were fortuitously discovered on upper endoscopy. The antral mucosa was thickened and polypoid, and on histologic examination contained immature granulocytes, megakaryocytes, and a few erythroblasts without desmoplastic stromal reaction. The granulocytes were positive for CD15, CD68, and myeloperoxidase on immunohistochemistry, and the megakaryocytes showed positive reactivity for factor VIII. Gastric myeloid metaplasia is a very rare event, and to our knowledge only 6 cases have been reported in the literature to date. It usually occurs in patients with advanced myeloproliferative syndrome. Gastric myeloid metaplasia often has a pseudotumoral appearance, leading to digestive symptoms. Histologic diagnosis is straightforward when trilinear hematopoietic elements are identified in gastric biopsies. Immunohistochemistry with anti-factor VIII antibody can be useful to confirm the presence of megakaryocytes.


Asunto(s)
Mucosa Gástrica , Mielofibrosis Primaria/patología , Anciano , Femenino , Mucosa Gástrica/patología , Humanos , Mielofibrosis Primaria/diagnóstico
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