RESUMEN
BACKGROUND: Progranulin is implicated in frontotemporal dementia (FTD), but its role in other neurodegenerative disorders is unknown. OBJECTIVE: To investigate the levels of progranulin (PGRN) in cerebrospinal fluid (CSF) in different neurodegenerative dementias and their correlation with levels in plasma in cognitively normal subjects. METHODS: We measured PGRN in CSF in 229 patients with amnestic mild cognitive impairment, Alzheimer's disease dementia, sporadic FTD, dementia with Lewy bodies, corticobasal syndrome, or progressive supranuclear palsy. We also measured PGRN in CSF and plasma in 74 cognitively normal individuals. We examined the correlation between PGRN levels in CSF and diagnosis, cortical thickness, genetic factors and other CSF biomarkers. We also investigated the correlation between plasma and CSF levels of PGRN in cognitively normal individuals. RESULTS: CSF levels did not differ across diagnoses or correlate with cortical thickness. Polymorphism rs5848 in GRN influenced CSF PGRN levels, but APOEÉ4 allele did not. Amyloid-ß42, t-tau, p-tau, and YKL-40 levels correlated weakly with PGRN in CSF. We found a weak correlation (râ=â0.362) between plasma and CSF PGRN levels in cognitively normal individuals. CONCLUSIONS: Our findings do not support a diagnostic value of CSF PGRN in neurodegenerative diseases. Our data confirm that levels of PGRN in plasma do not reflect accurately levels in CSF in cognitively normal controls. These data should be considered in clinical trials aiming to increase PGRN.
Asunto(s)
Demencia/líquido cefalorraquídeo , Péptidos y Proteínas de Señalización Intercelular/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Progranulinas , Proteínas tau/líquido cefalorraquídeoRESUMEN
BACKGROUND: Self-reported and informant-reported subjective cognitive decline (SCD) may be useful in the detection of preclinical Alzheimer's disease (Pre-AD) and cognitive impairment related to abnormal amyloid-ß (Aß 42) levels. OBJECTIVES: a) To compare the Subjective Cognitive Decline Questionnaire (SCD-Q) ratings between Pre-AD subjects and cognitively healthy controls, b) to study the association of SCD-Q scores with levels of AD biomarkers in cognitively healthy and cognitively impaired subjects, and c) to compare SCD-Q ratings in cognitively impaired subjects with or without abnormal Aß 42. METHODS: Two hundred and seventeen participants (111 subjects; 106 informants) answered the SCD-Q. All subjects underwent a lumbar puncture to determine levels of Aß 42 and tau, and an extensive neuropsychological battery. Healthy subjects were classified as Controls (CTR) or Pre-AD according to the absence or the presence of abnormal Aß 42, and those with cognitive impairment (CI) into Non-amyloid (NonAB-CI) or Amyloid (AB-CI) impairment. RESULTS: Informants' SCD-Q scores were significantly higher in the Pre-AD group than in the CTR group (Fâ=â6.75; pâ=â0.01). No significant differences were found in self-ratings. In the cognitively impaired groups, there were no significant differences in the SCD-Q ratings. In the whole sample, informants' ratings of SCD-Q correlated with Aß 42 (râ=â-0.21; pâ=â0.02) and tau levels (râ=â0.28; pâ=â0.00). CONCLUSIONS: Higher informants' ratings of SCD-Q differentiated Pre-AD subjects from CTR. Informants' ratings of SCD-Q correlated weakly with cerebrospinal fluid AD biomarkers.
Asunto(s)
Envejecimiento , Enfermedad de Alzheimer/diagnóstico , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Percepción/fisiología , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/líquido cefalorraquídeo , Análisis de Varianza , Enfermedades Asintomáticas/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Curva ROC , Autoinforme , Encuestas y Cuestionarios , Proteínas tau/líquido cefalorraquídeoRESUMEN
BACKGROUND/AIMS: Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular and cerebrovascular disease, and it has also been proposed as an independent risk factor for dementia and Alzheimer's disease (AD). Its relationship with cognitive impairment, however, remains unclear. We aimed to determine the relationship of tHcy levels with clinical diagnoses and cognitive performance in a sample of outpatients with cognitive impairment. METHODS: Plasma tHcy, folate, vitamin B12 and creatinine levels were assessed in individuals evaluated at the Memory Disorder Unit. Diagnoses included subjective memory complaints (SMC, n = 27), mild cognitive impairment (MCI, n = 142), AD (n = 139) and vascular dementia (VD, n = 17). All patients underwent extensive neuropsychological testing to evaluate attention, memory, language, and visuoconstructional and executive functions, as well as depression and impairments of daily living activities. RESULTS: tHcy levels did not differ between patients with SMC, MCI, AD or VD. Increased tHcy was associated with worse performance in geometric figure copy and clock drawing tests. CONCLUSIONS: tHcy levels did not discriminate between diagnostic groups of patients with cognitive impairments. Elevated tHcy levels in these patients appear to have a detrimental effect on visuoconstructional performance.