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OBJECTIVE: Despite recognition that people with HIV (PWH) are more vulnerable to sleep issues, there is limited understanding of clinically recognized sleep disorders in this population. Our objective was to evaluate the full spectrum of sleep disorder types diagnosed among PWH in care. METHODS: We conducted a retrospective cohort study of PWH, and a comparator group of people without HIV (PWoH), in a large healthcare system. The incidence of clinically diagnosed sleep disorders was calculated using Poisson regression for three outcomes: any type of sleep disorder, insomnia, and sleep apnea. Incidence was compared between PWH and PWoH by computing the adjusted incidence rate ratio (aIRR), accounting for sleep disorder risk factors. Comparisons to PWoH were made for all PWH combined, then with PWH stratified by HIV management status (well-managed HIV defined as being on antiretroviral therapy, HIV RNA <200 copies/mL, and CD4 count ≥500 cells/µL). RESULTS: The study included 9076 PWH and 205 178 PWoH (mean age 46 years, 90% men). Compared with PWoH, sleep disorder incidence was greater among PWH overall [aIRR = 1.19, 95% confidence interval (CI): 1.12-1.26], particularly for insomnia (aIRR = 1.56, 95% CI: 1.45-1.67). Sleep apnea incidence was lower among PWH (aIRR = 0.90, 95% CI: 0.84-0.97). In HIV management subgroups, PWH without well-managed HIV had lower sleep apnea incidence (vs. PWoH: aIRR = 0.79, 95% CI: 0.70-0.89) but PWH with well-managed HIV did not (vs. PWoH: aIRR = 0.97, 95% CI: 0.89-1.06). CONCLUSIONS: PWH have high sleep disorder incidence, and insomnia is the most common clinical diagnosis. Lower sleep apnea incidence among PWH may reflect underdiagnosis in those with sub-optimally treated HIV and will be important to investigate further.
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Background: Little is known about the prevalence of undiagnosed cognitive impairment and its impact on instrumental activities of daily living (IADL) among people with HIV (PWH) in primary care. Methods: PWH were recruited from an integrated health care setting in the United States. PWH were eligible for recruitment if they were ≥50 years old, taking antiretroviral therapy (ie, ≥1 antiretroviral therapy [ART] prescription fill in the past year), and had no clinical diagnosis of dementia. Participants completed a cognitive screen (St. Louis University Mental Status exam) and a questionnaire on IADL (modified Lawton-Brody). Results: Study participants (n = 47) were mostly male (85.1%), 51.1% White, 25.5% Black, 17.0% Hispanic, and the average age (SD) was 59.7 (7.0) years. Overall, 27 (57.5%) participants were categorized as cognitively normal, 17 (36.2%) as having mild cognitive impairment, and 3 (6.4%) as having possible dementia. Of the 20 participants with mild cognitive impairment or possible dementia, 85.0% were men, the average age (SD) was 60.4 (7.1) years; 45.0% were White, 40.0% were Black, 10.0% were Hispanic, and 30.0% reported difficulty with at least 1 IADL. Most (66.7%) attributed difficulty with IADL primarily (33.3%) or in part (33.3%) to cognitive problems. Conclusions: Undiagnosed cognitive impairment is frequent among ART-treated PWH, with possible elevated risk among Black PWH, and may be accompanied by difficulty with IADL. Efforts are needed to optimize identification of factors contributing to cognitive and IADL difficulties among ART-treated PWH in primary care.
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OBJECTIVE: To compare dementia incidence and prevalence after age 50 years by HIV status. DESIGN: Observational cohort, 2000-2016. METHODS: People with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWoH), all aged 50âyears and older, were identified from Kaiser Permanente healthcare systems in Northern California, Southern California, and Mid-Atlantic States (Maryland, Virginia, Washington DC). Dementia diagnoses were obtained from electronic health records. Incidence and prevalence of dementia, overall and by time period (i.e. 2000-2002, 2003-2004, , 2015-2016), were calculated using Poisson regression. Trends were examined using Joinpoint regression. Rate ratios were used to compare dementia by HIV status with adjustment for sociodemographics, substance use, and clinical factors. RESULTS: The study included 13â296 PWH and 155â354 PWoH (at baseline: for both, mean ageâ=â54âyears, 89% men; for PWH, 80% with HIV RNA <200âcopies/ml). From 2000 to 2016, overall incidence of dementia was higher among PWH [adjusted incidence rate ratio (aIRR)â=â1.80, 95% confidence interval (CI)â=â1.60-2.04]. Dementia incidence decreased among both PWH and PWoH (-8.0 and -3.1% per period, respectively) but remained higher among PWH in the most recent time period, 2015-2016 (aIRRâ=â1.58, 95% CIâ=â1.18-2.12). The overall prevalence of dementia from 2000 to 2016 was higher among PWH [adjusted prevalence ratio (aPR)â=â1.86, 95% CIâ=â1.70-2.04] and was also higher among PWH in 2015-2016 (aPRâ=â1.75, 95% CIâ=â1.56-1.97). CONCLUSION: Reductions in dementia incidence are encouraging and may reflect ART improvement, but PWH are still more likely to have dementia than PWoH. Monitoring the burden of dementia among PWH is important as this population ages.
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Demencia , Infecciones por VIH , Anciano , Demencia/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Atención Primaria de SaludRESUMEN
OBJECTIVE: To compare risk of dementia after age 50 by HIV status among individuals in a primary care setting. DESIGN: Observational cohort study; participants were identified from 2013 to 2017 and followed through 2019. METHODS: Participants were people with HIV (PWH) on antiretroviral therapy (ART) and demographically similar people without HIV (PWOH), all at least 50 years old and with no prior diagnosis of dementia. The study setting was Kaiser Permanente Northern California, an integrated healthcare delivery system in the United States. Incident dementia diagnoses and baseline data on sociodemographics, smoking, alcohol use, other substance use, and clinical factors were gathered from the electronic health record. Cumulative proportion of incident dementia by HIV status was assessed using Kaplan--Meier curves. Unadjusted and adjusted hazard ratios for incident dementia by HIV status were generated using Cox proportional hazards models with age as the time scale. RESULTS: The study included 5381 PWH and 119â022 PWOH (average age at baseline: 57 and 58 years, respectively). Incident dementia was diagnosed in 117 PWH and 2427 PWOH. By age 80, 25.8% of PWH and 13.8% of PWOH had been diagnosed with dementia, corresponding with an unadjusted hazard ratio of 1.98 (95% CI 1.64-2.39). After adjustment for sociodemographic, substance use, and clinical factors, including frequency of outpatient visits, the risk of dementia among PWH remained elevated (vs. PWOH, adjusted hazard ratio = 1.58, 95% CI 1.31-1.92). CONCLUSION: Compared with PWOH, PWH were at 58% higher risk for dementia despite HIV treatment with ART. Research is needed to investigate the potential benefits of targeted risk factor management or earlier cognitive screening in this population.
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Demencia , Infecciones por VIH , Anciano de 80 o más Años , Estudios de Cohortes , Demencia/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estados UnidosRESUMEN
Frontotemporal dementia (FTD) has rarely been reported in Chinese populations. There are many potential reasons for this, including possible hesitancy on the part of patients or families to bring FTD-related symptoms to medical attention. Here, we present data on eight Chinese individuals, all of whom met criteria for the behavioral variant of FTD or the semantic variant of primary progressive aphasia. These patients presented for neurological evaluation at a relatively advanced stage. The mean MMSE score at initial presentation was 15. Behavioral symptoms were common and usually elicited during the medical history only after direct questioning. Delay in presentation was attributed to a variety of issues, including family disagreements about whether the symptoms represented a disease and lack of medical insurance. These cases illustrate that the symptoms of FTD in Chinese-Americans are similar to those in Caucasians but various factors, some potentially culturally relevant, may influence the likelihood and timing of clinical presentation for FTD, as well as other dementias. Additional study of FTD in diverse ethnic groups needs to address barriers to clinical presentation, including factors that may be culturally specific.
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Demencia Frontotemporal/psicología , Anciano , Alcoholismo/complicaciones , Afasia Progresiva Primaria/psicología , Asiático , Pueblo Asiatico , Conducta , Encéfalo/patología , Corteza Cerebral/patología , Cultura , Progresión de la Enfermedad , Femenino , Demencia Frontotemporal/diagnóstico , Humanos , Lenguaje , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Pick/patología , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: To characterize dementia-induced changes in visual art production. BACKGROUND: Although case studies show altered visual artistic production in some patients with neurodegenerative disease, no case-controlled studies have quantified this phenomenon across groups of patients. METHOD: Forty-nine subjects [18 Alzheimer disease, 9 frontotemporal dementia (FTD), 9 semantic dementia (SD), 15 healthy older controls (NC)] underwent formal neuropsychologic testing of visuospatial, perceptual, and creative functioning, and produced 4 drawings. Subjective elements of drawings were rated by an expert panel that was blind to diagnosis. RESULTS: Despite equal performance on standard visuospatial tests, dementia groups produced distinct patterns of artistic features that were significantly different from NCs. FTDs used more disordered composition and less active mark-making (P<0.05). Both FTDs and SDs drawings were rated as more bizarre and demonstrated more facial distortion than NCs (P<0.05). Also, SDs drastically failed a standardized test of divergent creativity. Alzheimer disease artwork was more similar to controls than to FTDs or SDs, but showed a more muted color palette (P<0.05) and trends toward including fewer details, less ordered compositions, and occasional facial distortion. CONCLUSIONS: These group differences in artistic style likely resulted from disease-specific focal neurodegeneration, and elucidate the contributions of particular brain regions to the production of visual art.
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Enfermedad de Alzheimer/psicología , Arte , Creatividad , Demencia/psicología , Percepción Visual/fisiología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Demencia/clasificación , Femenino , Humanos , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valores de ReferenciaRESUMEN
BACKGROUND/AIMS: Research on dementia among ethnically diverse populations in the USA has focused primarily on Alzheimer disease and vascular dementia, but there are limited data on other neurodegenerative causes of dementia. METHODS: To determine the frequency of neurodegenerative disorders in four ethnic groups, data collected at Alzheimer's Disease Research Centers of California for assessments between 1992 and 2002 were analyzed retrospectively. Cases of Alzheimer disease, vascular dementia, dementia with Lewy bodies, frontotemporal lobar degeneration, Parkinson disease and progressive supranuclear palsy were identified for 452 Asian and Pacific Islander, 472 Black, 675 Latino and 4,926 White patients. RESULTS: The percentage of non-Whites diagnosed as having dementia with Lewy bodies was lower than that of Whites. Frontotemporal lobar degeneration was as common in Asians and Pacific Islanders compared to Whites, but less common in Blacks and Latinos. Progressive supranuclear palsy was more frequent in Asians and Pacific Islanders compared to Whites, but equally common in Blacks and Latinos. CONCLUSION: Additional study is needed on the social and biological factors that influence the diagnosis and prevalence of non-Alzheimer and nonvascular dementias among diverse ethnic groups.
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Demencia/epidemiología , Demencia/etiología , Etnicidad/estadística & datos numéricos , Edad de Inicio , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/etiología , Asiático/estadística & datos numéricos , Población Negra/estadística & datos numéricos , Demencia/clasificación , Educación , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Pruebas Neuropsicológicas , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Cases of early-onset Alzheimer disease (AD) with an autosomal dominant inheritance pattern (familial AD [FAD]) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We describe herein a kindred with very early-onset FAD (age, <40 years) with unusual pathological features and a novel mutation in the presenilin 1 (PSEN1) gene (S170F) and review the existing literature on very early-onset FAD. OBJECTIVE: To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life. DESIGN, SETTING, AND PARTICIPANTS: The proband underwent full clinical assessment and postmortem examination at the Washington University Alzheimer's Disease Research Center, St Louis, Mo. Limited pathological samples and autopsy records of 2 affected family members were available. The proband underwent screening for mutations in genes linked with FAD. RESULTS: Dementia developed in 3 family members in this kindred at a mean age of 27 years; the proband had myoclonus, seizures, and rigidity, similar to findings in previously described kindreds with PSEN1 mutations. All 3 family members were confirmed to have AD by neuropathological examination. The proband also had widespread Lewy body pathology in the brainstem, limbic areas, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. The proband had a single mutation (S170F) in exon 6 of the PSEN1 gene, which segregates with disease. CONCLUSIONS: A novel PSEN1 mutation causes very-early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies.
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Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad/genética , Cuerpos de Lewy/genética , Enfermedad por Cuerpos de Lewy/genética , Proteínas de la Membrana/genética , Mutación/genética , Adulto , Edad de Inicio , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Sustitución de Aminoácidos/genética , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/patología , Trastornos de los Cromosomas/fisiopatología , Progresión de la Enfermedad , Exones/genética , Salud de la Familia , Resultado Fatal , Femenino , Humanos , Cuerpos de Lewy/metabolismo , Enfermedad por Cuerpos de Lewy/patología , Enfermedad por Cuerpos de Lewy/fisiopatología , Masculino , Ovillos Neurofibrilares/genética , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Linaje , Placa Amiloide/genética , Placa Amiloide/metabolismo , Placa Amiloide/patología , Presenilina-1 , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMEN
BACKGROUND: Several studies have found impaired recall of remote autobiographical memories relative to recent memories in semantic dementia (SD), a pattern opposite to that in Alzheimer's disease (AD). OBJECTIVE: To document dissociation of memory for autobiographical incidents and personal semantic information in individuals with AD, frontotemporal dementia (FTD), and SD. METHODS: The authors administered the Autobiographical Memory Interview to eight individuals with AD, 11 with FTD, eight with SD, and eight normal controls . Autobiographical incidents and personal semantic memory was assessed from three time periods: childhood, early adulthood, and recent life. RESULTS: Individuals with SD recalled more details of autobiographical incidents from the most recent 5 years than from childhood and early adulthood (childhood vs recent life: t(7) = -3.59, p = 0.009; early adulthood vs recent life: t(7) = -4.33, p = 0.003). No difference was found between childhood and early adulthood (t(7) = 1.11, p = 0.305). Recall of personal semantic information was related to the age of the memory with less remembered from earlier time periods (childhood vs recent life: t(7) = -6.52, p < 0.001; childhood vs early adulthood: t(7) = -2.61, p = 0.035; early adulthood vs recent life: t(7) = -9.15, p < 0.001). CONCLUSIONS: SD is a compelling model in which to study the anatomy of episodic memory.
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Enfermedad de Alzheimer/psicología , Demencia/psicología , Trastornos de la Memoria/etiología , Recuerdo Mental , Anciano , Anciano de 80 o más Años , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Autoimagen , SemánticaRESUMEN
Alzheimer disease (AD) is a neurodegenerative disease that is currently not preventable or curable. Early-onset AD can be due to mutations in several autosomal dominant genes. Clinical testing is available for presenilin 1 (PS1), which is the most common of these genes. However, many practical and ethical issues must be considered before ordering this test for patients with early-onset AD. In this paper, we present a case that demonstrates the complexities of genetic testing for early-onset AD.
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Enfermedad de Alzheimer/genética , Pruebas Genéticas , Enfermedad de Alzheimer/diagnóstico , Apolipoproteína E4 , Apolipoproteínas E/genética , Atrofia , Corteza Cerebral/patología , Aberraciones Cromosómicas , Análisis Mutacional de ADN , Ética Médica , Femenino , Financiación Personal/economía , Financiación Personal/ética , Genes Dominantes , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas/economía , Pruebas Genéticas/ética , Humanos , Proteínas de la Membrana/genética , Escala del Estado Mental/estadística & datos numéricos , Persona de Mediana Edad , Presenilina-1 , PsicometríaRESUMEN
As a uniquely human talent that has evolved from prehistoric cave paintings, art draws on many brain areas responsible for various cognitive processes. The pattern of degeneration in dementia leads to predictable changes in art. The visuospatial deficits in Alzheimer disease lead to less precision and attention to spatial relationships. In some cases of frontotemporal dementia, artistic creativity appears anew as the disease develops. The artwork is approached in a compulsive manner and is often realistic or surrealistic in style. Art in the context of dementia provides a unique window into the cognitive processes of various brain regions and an opportunity for rehabilitation.
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Creatividad , Demencia/patología , Medicina en las Artes , Pinturas/psicología , Demencia/psicología , Demencia/rehabilitación , Humanos , Percepción Visual/fisiologíaRESUMEN
OBJECTIVE: To review the clinical and molecular features of non-Alzheimer's disease (non-AD) dementias, focusing on disorders associated with tau pathology (that is, frontotemporal lobar degeneration [FTLD], corticobasal ganglionic degeneration [CBD], and progressive supranuclear palsy [PSP]) or on disorders with synuclein pathology (that is, dementia with Lewy bodies [DLB] and multisystem atrophy [MSA]). We also discuss the pharmacologic treatment of these disorders. METHODS: We report a selective review of the literature on FTLD, CBD, PSP, DLB, and MSA. RESULTS: The non-AD dementias can present with a wide variety of cognitive and behavioural symptoms. Through common clinical features and shared molecular etiologies, neurodegenerative disorders previously thought to be distinct are now classified into tauopathies and synucleinopathies. CONCLUSIONS: The unique cognitive and behavioural manifestations of the non-AD dementias can be mistaken for psychiatric disorders. Improved detection of tauopathies and synucleinopathies and their differentiation from AD is possible.
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Demencia/genética , Proteínas del Tejido Nervioso/genética , Tauopatías/genética , Proteínas tau/genética , Enfermedad de Alzheimer/diagnóstico , Encéfalo/patología , Demencia/diagnóstico , Demencia/patología , Diagnóstico Diferencial , Humanos , Sinucleínas , Tauopatías/diagnóstico , Tauopatías/patologíaRESUMEN
Dystonia associated with chromosomal abnormalities is typically attributed to chromosomal deletions. We describe a patient with ring chromosome 21, with karyotype 46XX,r(21)(p11.2q22.3); 46,XX,dic r(21)(p11.2q22.3); 45, XX, -21, who developed childhood onset cervical dystonia.