RESUMO
Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP, PSEN1, PSEN2, MAPT, GRN, and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1, 11 MAPT, 9 PSEN2, and 4 APP. Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.
Assuntos
Doença de Alzheimer , Demência Frontotemporal , Mutação , Proteínas tau , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/epidemiologia , Itália/epidemiologia , Demência Frontotemporal/genética , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Proteínas tau/genética , Idade de Início , Proteína C9orf72/genética , Presenilina-2/genética , Estudos Retrospectivos , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética , Progranulinas/genética , Adulto , Idoso de 80 Anos ou mais , Predisposição Genética para DoençaRESUMO
Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.
Assuntos
Demência , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Estudos Retrospectivos , China/epidemiologia , Pessoa de Meia-Idade , Idoso , Demência/epidemiologia , Demência/etiologia , Progressão da Doença , Doença de Alzheimer/epidemiologia , Neurossífilis/epidemiologia , Neurossífilis/complicações , Síndrome de Creutzfeldt-Jakob/epidemiologia , Demência Frontotemporal/epidemiologia , Encefalite/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Idoso de 80 Anos ou mais , Doenças Neurodegenerativas/epidemiologiaRESUMO
Background: Psychosis, characterized by delusions and/or hallucinations, is frequently observed during the progression of Alzheimer's disease (AD) and other neurodegenerative dementias (ND) (i.e., dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD)) and cause diagnostic and management difficulties. Objective: This review aims at presenting a concise and up-to-date overview of psychotic symptoms that occur in patients with ND with a comparative approach. Methods: A systematic review was conducted following the PRISMA guidelines. 98 original studies investigating psychosis phenotypes in neurodegenerative dementias were identified (40 cohort studies, 57 case reports). Results: Psychosis is a frequently observed phenomenon during the course of ND, with reported prevalence ranging from 22.5% to 54.1% in AD, 55.9% to 73.9% in DLB, and 18% to 42% in FTD. Throughout all stages of these diseases, noticeable patterns emerge depending on their underlying causes. Misidentification delusions (16.6-78.3%) and visual hallucinations (50-69.6%) are frequently observed in DLB, while paranoid ideas and somatic preoccupations seem to be particularly common in AD and FTD, (respectively 9.1-60.3% and 3.10-41.5%). Limited data were found regarding psychosis in the early stages of these disorders. Conclusions: Literature data suggest that different ND are associated with noticeable variations in psychotic phenotypes, reflecting disease-specific tendencies. Further studies focusing on the early stages of these disorders are necessary to enhance our understanding of early psychotic manifestations associated with ND and help in differential diagnosis issues.
Assuntos
Transtornos Psicóticos , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/psicologia , Doenças Neurodegenerativas/diagnóstico , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/psicologia , Doença por Corpos de Lewy/epidemiologia , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/epidemiologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/psicologia , Doença de Alzheimer/complicações , Delusões/diagnóstico , Delusões/epidemiologia , Delusões/etiologia , Demência/epidemiologia , Demência/diagnósticoRESUMO
BACKGROUND: Studies have shown that the prevalence of all-variants Alzheimer's disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way. METHODS: We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations. RESULTS: The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40-44 age group to 1411/1,000,000 in the 60-64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence. CONCLUSIONS: Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease.
Assuntos
Idade de Início , Doença de Alzheimer , Demência Frontotemporal , Humanos , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/diagnóstico , Prevalência , Pessoa de Meia-Idade , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/diagnóstico , Masculino , Feminino , Itália/epidemiologia , Adulto , Idoso , Fatores EtáriosRESUMO
BACKGROUND: Major depressive disorder (MDD) and dementia psychiatric and neurological diseases that are clinically widespread, but whether there is a causal link between them is still unclear. In this study, bidirectional two-sample Mendelian randomization (MR) was used to investigate the potential causal relationship between MDD and dementia via a genome-wide association study (GWAS) database, containing samples from the European population. METHOD: We collected data on MDD and common clinical dementia subtypes from GWAS, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and vascular dementia (VaD). A series of bidirectional two-sample MR studies and correlation sensitivity analysis were carried out. RESULTS: In the study of the effect of MDD on dementia subtypes, no causal relationship was found between MDD and dementia subtypes other than VaD, inverse variance weighted (IVW) method: odds ratio (OR), 2.131; 95 % confidence interval (CI), 1.249-3.639, P = 0.006; MDD-AD: OR, 1.000; 95 % CI, 0.999-1.001, P = 0.537; MDD-FTD: OR, 1.476; 95 % CI, 0.471-4.627, P = 0.505; MDD-PDD: OR, 0.592; 95 % CI, 0.204-1.718, P = 0.335; MR-Egger method: MDD-DLB: OR, 0.582; 95 % CI, 0.021-15.962, P = 0.751. In reverse MR analyses, no dementia subtype was found to be a risk factor for MDD. LIMITATIONS: The results of this study may not be generalizable to non-European populations. CONCLUSION: MDD was identified as a potential risk factor for VaD, but no dementia subtype was found to be a risk factor for MDD. These results suggest a new avenue for the prevention of VaD.
Assuntos
Doença de Alzheimer , Transtorno Depressivo Maior , Demência Frontotemporal , Humanos , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização MendelianaRESUMO
Frontotemporal dementia (FTD) is a progressive decline of cognitive abilities associated with other neuropsychiatric comorbidities. A real-world data (RWD) analysis of a large electronic healthcare records (EHR) database identified the comorbidities of FTD. Deidentified EHRs in the TriNetX Network database from >155,000,000 individuals in the United States established an FTD Cohort (ICD-10 Code G31.0) of adult patients who visited a healthcare provider in 2022. The non-FTD cohort were age-matched individuals who had not received a diagnosis of ICD-10 Code G31.0, and who had visited a healthcare provider in 2022. The median age of both cohorts was 73 years. A comparative analysis was performed between the FTD and non-FTD cohorts. There were 6660 individuals (aged ≥18) with FTD and 11,810,060 individuals (aged ≥63) without a diagnosis of FTD, with healthcare visits in 2022. There were 25 ICD-10 Codes for disorders that were present in >10% of FTD patients, with a Relative Risk (RR) of ≥2.0 compared the non-FTD cohort. Multiple neuropsychiatric disorders had RRs ≥ 2.0, with minimal evidence for significant involvement of other organ systems. These data document that FTD, as known previously, is associated with multiple neuropsychiatric comorbidities. There was minimal evidence of comorbid involvement of other organ systems. These data provide a baseline of general FTD symptoms for the rapidly evolving analysis of genetic subvariants of FTD. These data also provide insights into the clinical management of FTD, as well as recommendations for specific endpoints in clinical trials.
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Demência Frontotemporal , Adulto , Humanos , Idoso , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/psicologia , Cognição , Pessoal de Saúde , Análise de DadosRESUMO
INTRODUCTION: The psychological and behavioral symptoms of dementia are frequently observed in clinical practice, and those related to sexuality are particularly challenging. However, few studies have evaluated the prevalence or factors associated with hypersexuality in patients with dementia. OBJECTIVES: This study aims to determine the prevalence of hypersexuality in patients with dementia, describe associated factors, and qualitatively report the most common presentations and treatments. METHODS: This retrospective cross-sectional study collected data from semi-structured charts of dementia patients who were followed up at a secondary care reference center between 2015 and 2019. Results: Of 552 total patients, 52 (9.3%) were hypersexual, which was associated with male sex (P < .000; OR 2.95, 95% CI 1.73-5.01), frontotemporal dementia (P < .007), alcohol use (P < .015; OR 2.35, 95% CI 1.16-4.73) and tobacco use (P < .000; OR 2.88, 95% CI 1.61-5.13). CONCLUSIONS: Although our findings were similar to the literature, their significant variability reflects the limited and low quality of the available evidence and a lack of standardization regarding terminology, definitions, and diagnostic criteria for hypersexuality.
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Demência , Humanos , Masculino , Estudos Transversais , Estudos Retrospectivos , Feminino , Idoso , Prevalência , Demência/epidemiologia , Idoso de 80 Anos ou mais , Disfunções Sexuais Psicogênicas/epidemiologia , Disfunções Sexuais Psicogênicas/psicologia , Pessoa de Meia-Idade , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/psicologia , Comportamento Sexual/psicologia , Fatores SexuaisRESUMO
BACKGROUND: Amyotrophic lateral sclerosis overlaps aetiologically and genetically with frontotemporal dementia and occurs in both familial and apparently sporadic forms. The most commonly implicated genes are C9orf72, SOD1, TARDBP and FUS. Penetrance of disease-causing variants in these genes is known to be incomplete, but has not been well studied at population level. OBJECTIVE: We sought to determine the population-level penetrance of pathogenic and likely pathogenic variants in genes commonly causing amyotrophic lateral sclerosis. METHODS: Published epidemiological data for amyotrophic lateral sclerosis and frontotemporal dementia were used to calculate expected frequencies of disease-causing variants per gene at population level. Variant data from gnomAD and ClinVar databases were used to ascertain observed numbers of disease-causing variants and to estimate population-level penetrance per gene. Data for C9orf72 were obtained from the published literature. RESULTS: Maximum population penetrance for either amyotrophic lateral sclerosis or frontotemporal dementia was found to be 33% for C9orf72 (95% CI (20.9 to 53.2)), 54% for SOD1 (95% CI (32.7 to 88.6)), 38% for TARDBP (95% CI (21.1 to 69.8)) and 19% for FUS (95% CI (13.0 to 28.4)). CONCLUSION: Population-level penetrance of amyotrophic lateral sclerosis disease genes is reduced. This finding has implications for the genetic testing and counselling of affected individuals and their unaffected relatives.
Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Humanos , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/genética , Proteína C9orf72/genética , Penetrância , Superóxido Dismutase-1/genéticaRESUMO
Background: Front temporal dementias (FTD) are neurodegenerative disorders characterized by alterations in behavior, affection and language, with relative sparing of episodic memory. There are three major forms of FTD: the frontal or behavioral form, progressive non-fluent aphasia and semantic dementia (that may begin as a fluent progressive aphasia). Aim: To report a retrospective clinical experience of patients with frontotemporal dementia. Material and methods: Review of 3,700 records of neuropsychological assessments of patients with behavioral disturbances, studied between 1981 and 2008. Of these, 63 patients (59 percent females) complied with the criteria for frontotemporal dementia. Results: There were 47 cases with the frontal variant, four with non-fluent progressive aphasia and six with fluent progressive aphasias (2 evolved to semantic dementia). The mean age of onset was 60±11 years. There were no familiar cases of FTD. Conclusions: It is clinically difficult to diagnose FTD, since evaluation of attitude or language is required. In addition to structural images, functional images were helpful in some cases, but the definitive diagnosis is anatomical.