RESUMO
BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.
Assuntos
Disfunção Cognitiva , Demência , Doença de Parkinson , Cognição , Disfunção Cognitiva/epidemiologia , Humanos , Estilo de Vida , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologiaAssuntos
Doenças Autoimunes do Sistema Nervoso/diagnóstico , Moléculas de Adesão Celular Neuronais/imunologia , Fatores Imunológicos/farmacologia , Doenças Neurodegenerativas/diagnóstico , Idoso , Animais , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Feminino , Células HEK293 , Humanos , Imunoterapia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia , RatosRESUMO
Frontotemporal lobar degeneration caused by GRN mutations is mainly associated with a TDP-43 type A proteinopathy. We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p.Trp2*) in which the proband's brain also showed prominent glial tauopathy consistent with an aging-related tau astrogliopathy. Astrocytic tauopathy, 4R(+) and 3R(-) immunoreactive, was characterized by thorn-shaped astrocytes present in subpial, subependymal, and perivascular areas, and in gray matter; plus granular or fuzzy tau immunoreactivity in astrocytic processes in gray matter, either solitary or clustered in different regions. Some neurofibrillary tangles and pretangles, both 3R and 4R(+), were present in the medial temporal lobe but did not exhibit the characteristic distribution of Alzheimer's type pathology. This 4R-tau aging-related tau astrogliopathy is likely a co-occurring pathology, although an interaction between progranulin and tau proteins within the neurodegenerative process should not be ruled out.
Assuntos
Astrócitos/metabolismo , Astrócitos/patologia , Códon sem Sentido/genética , Demência Frontotemporal/genética , Estudos de Associação Genética , Progranulinas/genética , Tauopatias/genética , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Genes Dominantes/genética , Humanos , Masculino , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/genética , Emaranhados Neurofibrilares/metabolismo , Tauopatias/metabolismo , Tauopatias/patologiaRESUMO
The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.
Assuntos
Doença de Alzheimer/genética , Proteínas Relacionadas a Receptor de LDL/genética , Proteínas de Membrana Transportadoras/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , Irmãos , EspanhaRESUMO
For diagnostic purposes, we screened for the C9ORF72 mutation in a) 162 FTLD cases, and b) 145 cases with other diagnoses but with some frontotemporal features or manifestations previously reported in C9 carriers. Ten cases (onset 50 to 75 years) harbored the expansion: seven had FTLD syndromes (4.3% of total, 11% of familial cases), and three (2%) had a different diagnosis. All positive cases had family history of dementia, psychiatric disease, or ALS, but only 20% of families with mixed FTLD/ALS phenotypes carried the expansion. Language impairment was the most common symptom, followed by behavioral changes, memory deficits, and parkinsonism. C9ORF72 mutation has a low frequency in our dementia series and very diverse clinical manifestations.
Assuntos
Cognição , Expansão das Repetições de DNA , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/psicologia , Proteínas/genética , Adulto , Idade de Início , Apolipoproteína E4/genética , Proteína C9orf72 , Família , Feminino , Seguimentos , Degeneração Lobar Frontotemporal/epidemiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologiaRESUMO
BACKGROUND: Patients with primary progressive aphasia (PPA) usually develop significant behavioral disturbances with progression of the disease. We tested our clinical observation that development of disruptive agitation is more likely in semantic than in nonfluent PPA and examined which clinical variables could be associated with this behavior. METHODS: We retrospectively analyzed neuropsychiatric scores and the need for behavioral treatments in semantic PPA (n = 41) and nonfluent PPA (n = 39) cases and compared first (1-3 years since the onset of symptoms) and last (5-13 years since the onset) evaluations. Clinical variables and laterality of temporal atrophy were associated with symptoms in semantic PPA cases. RESULTS: The semantic PPA group developed more frequent (p = 0.03) and intense agitation (p = 0.0008) and had a greater need for antipsychotic drugs (p = 0.001) than the nonfluent PPA group. Presence of agitation was clearly associated with psychotic symptoms (delusions/hallucinations) but was not associated with gender, age at onset, duration of the disease, or laterality of temporal atrophy. In contrast, nonfluent PPA cases were more frequently depressed and treated with antidepressants (p = 0.0007). There were no differences in anxiety, irritability, apathy, perseverations, hyperorality, or abnormal motor behavior. CONCLUSIONS: Semantic PPA in advanced disease is frequently associated with agitation and psychotic symptoms with fewer mood symptoms, while nonfluent PPA maintains a high prevalence of depression. This implies different treatment and care and support needs for each group.
Assuntos
Afasia Primária Progressiva/psicologia , Delusões/etiologia , Depressão/etiologia , Afasia Primária Progressiva não Fluente/psicologia , Agitação Psicomotora/etiologia , Idoso , Atrofia , Delusões/diagnóstico , Depressão/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Agitação Psicomotora/diagnóstico , Estudos Retrospectivos , Lobo TemporalAssuntos
Transtornos da Cefaleia Primários/complicações , Transtornos da Cefaleia/fisiopatologia , Enxaqueca sem Aura/complicações , Causalidade , Progressão da Doença , Feminino , Frutose/análogos & derivados , Frutose/uso terapêutico , Transtornos da Cefaleia/tratamento farmacológico , Transtornos da Cefaleia Primários/fisiopatologia , Humanos , Hiperacusia/etiologia , Pessoa de Meia-Idade , Enxaqueca sem Aura/tratamento farmacológico , Enxaqueca sem Aura/fisiopatologia , Modelos Neurológicos , Náusea/etiologia , Nociceptores/fisiologia , Fotofobia/etiologia , Topiramato , Pontos-Gatilho/fisiopatologiaRESUMO
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