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1.
Neurology ; 96(1): e81-e92, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33093220

RESUMO

OBJECTIVE: To determine the associations between amyloid-PET, tau-PET, and atrophy with the behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms. METHODS: We assessed 15 patients with behavioral/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 patients with disease severity- and age-matched amnestic AD and a group of 131 cognitively unimpaired (CU) elderly individuals. All participants were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI, and neuropsychological testing. RESULTS: Voxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioral/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate, and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the receiver operating characteristic curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate, and frontal insular cortices were best able to differentiate between behavioral/dysexecutive and amnestic AD (area under the curve 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction. CONCLUSIONS: Our results provide evidence of frontal cortical involvement of tau pathology in behavioral/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Transtornos Mentais/patologia , Proteínas tau/metabolismo , Idoso , Doença de Alzheimer/complicações , Atrofia/patologia , Feminino , Humanos , Masculino , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Neuroimagem/métodos , Fenótipo
2.
J Alzheimers Dis ; 78(4): 1775-1782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33285638

RESUMO

BACKGROUND: The emergence of the coronavirus disease 2019 (COVID-19) has brought large challenges to dementia patients. We reviewed the existing literature on COVID-19 to assess the incidence and mortality of dementia comorbidities in COVID-19 patients. OBJECTIVE: To investigate the impact of pre-existing dementia comorbidities on COVID-19. METHODS: We searched the PubMed, Embase, and Web of Science databases for patients with preexisting dementia who were diagnosed with COVID-19. The statistical data on the prevalence and mortality of dementia comorbidities were examined. A fixed-or random-effect model was used to calculate the overall pooled risk estimates. Forest plots were generated to show the summarized results. RESULTS: A total of 265 articles were retrieved from the three databases. After removing duplicates and performing two screenings, 10 articles were selected for meta-analysis, including 119,218 participants. Overall, the meta-analysis of the 10 studies showed that the incidence of dementia in COVID-19 patients was (R: 9%, [95% CI: 6% to 13%]). Moreover, the meta-analysis of 9 studies showed that the mortality rate of individuals with dementia after being infected with COVID-19 was higher than that of individuals with no dementia (OR: 5.17 [95% CI: 2.31 to 11.59]). Substantial heterogeneity was observed in this meta-analysis. Significant publication bias was also found. CONCLUSION: Emerging literature shows that dementia comorbidities are a high risk factor for the prevalence and mortality of COVID-19. Our results should have an impact on preventive interventions and encourage more targeted approaches to prioritize older people with specific risk factors, such as dementia.


Assuntos
/complicações , Demência/complicações , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/mortalidade , /mortalidade , Demência/epidemiologia , Demência/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento
4.
Clin Interv Aging ; 15: 2407-2414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380791

RESUMO

Purpose: The current study aimed 1) to assess laypersons' priority-setting preferences for allocating ventilators to COVID-19 patients with and without AD while differentiating between a young and an old person with the disease, and 2) to examine the factors associated with these preferences. Methods: A cross-sectional online survey was conducted among a sample of 309 Israeli Jewish persons aged 40 and above. Results: Overall, almost three quarters (71%) of the participants chose the 80-year-old patient with a diagnosis of AD to be the last to be provided with a ventilator. The preferences of the remaining quarter were divided between the 80-year-old person who was cognitively intact and the 55-year-old person with AD. Education and subjective knowledge about AD were significantly associated with participants' preferences. Conclusion: Our results suggest that cognitive status might not be a strong discriminating factor for laypersons' preferences for allocating ventilators during the COVID-19 pandemic.


Assuntos
Doença de Alzheimer/complicações , /terapia , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventiladores Mecânicos
5.
Cochrane Database Syst Rev ; 11: CD009178, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189083

RESUMO

BACKGROUND: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant carer distress, increased healthcare costs, and institutionalisation. Although non-drug interventions are recommended as the first-line approach to managing these problems, drug treatment is often sought and used. However, there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this clinically vulnerable population. OBJECTIVES: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia. SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 19 February 2020, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, and sundowning. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, risk of bias, and results. We used the mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CI) as the measures of treatment effect, and where possible, synthesised results using a fixed-effect model. Key outcomes to be included in our summary tables were chosen with the help of a panel of carers. We used GRADE methods to rate the certainty of the evidence. MAIN RESULTS: We found nine eligible RCTs investigating: melatonin (5 studies, n = 222, five studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), the sedative antidepressant trazodone (1 study, n = 30), the melatonin-receptor agonist ramelteon (1 study, n = 74, no peer-reviewed publication), and the orexin antagonists suvorexant and lemborexant (2 studies, n = 323). Participants in the trazodone study and most participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study and the orexin antagonist studies had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. Primary sleep outcomes were measured using actigraphy or polysomnography. In one study, melatonin treatment was combined with light therapy. Only four studies systematically assessed adverse effects. Overall, we considered the studies to be at low or unclear risk of bias. We found low-certainty evidence that melatonin doses up to 10 mg may have little or no effect on any major sleep outcome over eight to 10 weeks in people with AD and sleep disturbances. We could synthesise data for two of our primary sleep outcomes: total nocturnal sleep time (TNST) (MD 10.68 minutes, 95% CI -16.22 to 37.59; 2 studies, n = 184), and the ratio of day-time to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; 2 studies; n = 184). From single studies, we found no evidence of an effect of melatonin on sleep efficiency, time awake after sleep onset, number of night-time awakenings, or mean duration of sleep bouts. There were no serious adverse effects of melatonin reported. We found low-certainty evidence that trazodone 50 mg for two weeks may improve TNST (MD 42.46 minutes, 95% CI 0.9 to 84.0; 1 study, n = 30), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; 1 study, n = 30) in people with moderate-to-severe AD. The effect on time awake after sleep onset was uncertain due to very serious imprecision (MD -20.41 minutes, 95% CI -60.4 to 19.6; 1 study, n = 30). There may be little or no effect on number of night-time awakenings (MD -3.71, 95% CI -8.2 to 0.8; 1 study, n = 30) or time asleep in the day (MD 5.12 minutes, 95% CI -28.2 to 38.4). There were no serious adverse effects of trazodone reported. The small (n = 74), phase 2 trial investigating ramelteon 8 mg was reported only in summary form on the sponsor's website. We considered the certainty of the evidence to be low. There was no evidence of any important effect of ramelteon on any nocturnal sleep outcomes. There were no serious adverse effects. We found moderate-certainty evidence that an orexin antagonist taken for four weeks by people with mild-to-moderate AD probably increases TNST (MD 28.2 minutes, 95% CI 11.1 to 45.3; 1 study, n = 274) and decreases time awake after sleep onset (MD -15.7 minutes, 95% CI -28.1 to -3.3: 1 study, n = 274) but has little or no effect on number of awakenings (MD 0.0, 95% CI -0.5 to 0.5; 1 study, n = 274). It may be associated with a small increase in sleep efficiency (MD 4.26%, 95% CI 1.26 to 7.26; 2 studies, n = 312), has no clear effect on sleep latency (MD -12.1 minutes, 95% CI -25.9 to 1.7; 1 study, n = 274), and may have little or no effect on the mean duration of sleep bouts (MD -2.42 minutes, 95% CI -5.53 to 0.7; 1 study, n = 38). Adverse events were probably no more common among participants taking orexin antagonists than those taking placebo (RR 1.29, 95% CI 0.83 to 1.99; 2 studies, n = 323). AUTHORS' CONCLUSIONS: We discovered a distinct lack of evidence to guide decisions about drug treatment of sleep problems in dementia. In particular, we found no RCTs of many widely prescribed drugs, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks for these common treatments. We found no evidence for beneficial effects of melatonin (up to 10 mg) or a melatonin receptor agonist. There was evidence of some beneficial effects on sleep outcomes from trazodone and orexin antagonists and no evidence of harmful effects in these small trials, although larger trials in a broader range of participants are needed to allow more definitive conclusions to be reached. Systematic assessment of adverse effects in future trials is essential.


Assuntos
Doença de Alzheimer/complicações , Transtornos do Sono-Vigília/tratamento farmacológico , Azepinas/efeitos adversos , Azepinas/uso terapêutico , Cognição/efeitos dos fármacos , Humanos , Indenos/efeitos adversos , Indenos/uso terapêutico , Melatonina/efeitos adversos , Melatonina/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono/efeitos dos fármacos , Sono/fisiologia , Transtornos do Sono-Vigília/etiologia , Fatores de Tempo , Trazodona/efeitos adversos , Trazodona/uso terapêutico , Triazóis/efeitos adversos , Triazóis/uso terapêutico
6.
Nat Commun ; 11(1): 6024, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247134

RESUMO

The availability of blood-based assays detecting Alzheimer's disease (AD) pathology should greatly accelerate AD therapeutic development and improve clinical care. This is especially true for markers that capture the risk of decline in pre-symptomatic stages of AD, as this would allow one to focus interventions on participants maximally at risk and at a stage prior to widespread synapse loss and neurodegeneration. Here we quantify plasma concentrations of an N-terminal fragment of tau (NT1) in a large, well-characterized cohort of clinically normal elderly who were followed longitudinally. Plasma NT1 levels at study entry (when all participants were unimpaired) were highly predictive of future cognitive decline, pathological tau accumulation, neurodegeneration, and transition to a diagnosis of MCI/AD. These predictive effects were particularly strong in participants with even modestly elevated brain ß-amyloid burden at study entry, suggesting plasma NT1 levels capture very early cognitive, pathologic and neurodegenerative changes along the AD trajectory.


Assuntos
Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Degeneração Neural/sangue , Degeneração Neural/complicações , Proteínas tau/sangue , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/sangue , Disfunção Cognitiva/complicações , Disfunção Cognitiva/fisiopatologia , Feminino , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Memória Episódica , Degeneração Neural/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
7.
Medicine (Baltimore) ; 99(45): e23076, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157972

RESUMO

BACKGROUND: This study will appraise the clinical efficacy of sertraline in the treatment of depression caused by Alzheimer disease (AD). METHODS: Comprehensive searches in PUBMED, EMBASE, Cochrane Library, Scopus, AMED, CNKI, and WANGFANG will be performed from inception to the present without language restriction. In addition, other sources will also be searched to avoid losing more potential studies. We will only consider randomized controlled trials that examined the efficacy of sertraline for depression in patients with AD. Two team members will independently undertake literature selection, data collection, and risk of bias assessment. We will use Cochrane Risk of Bias Tool to assess the risk of bias for each eligible trial, and will utilize RevMan 5.3 software to carry out data analysis. RESULTS: This study will recapitulate high-quality evidence to assess the efficacy of sertraline for the treatment of depression following AD. CONCLUSION: The findings of this study will help to determine whether or not sertraline is effective for the treatment of depression after AD. OSF REGISTRATION:: osf.io/f29v6.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Projetos de Pesquisa , Sertralina/uso terapêutico , Revisões Sistemáticas como Assunto , Doença de Alzheimer/complicações , Depressão/etiologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Artigo em Russo | MEDLINE | ID: mdl-33081441

RESUMO

OBJECTIVE: To study the relationship between cognitive deficits and retinal neuroarchitectonics in Alzheimer's disease, vascular dementia, and glaucoma based on optical coherence tomography. MATERIAL AND METHODS: A comprehensive examination of 90 patients with Alzheimer's disease, vascular dementia and glaucoma was conducted. The patients were divided into three groups of 30 people each. The groups were comparable by gender and age and initial socio-economic status. All patients underwent a comprehensive neurological and neuropsychological study as well as optical coherence tomography. RESULTS AND CONCLUSION: The results of optical coherence tomography in Alzheimer's disease and glaucoma reveal retinal changes in the perifocal region in the upper and lower quadrants. In patients with vascular dementia, the process is observed in the foveal (central) region of the retina, which can be considered as a potential biomarker of the neurodegenerative damage. The severity of cognitive deficit in the Alzheimer's disease group correlates with the degree of degeneration in the layers of the peripapillary layer of the nerve fibers of the retina of the temporal region, the perifocal region of the lower quadrant of the retina, ganglion cells, and the inner plexiform layers of the retina. In the vascular dementia group, the severity of cognitive deficit positively correlates with the degree of cell degeneration in the foveal region of the inner plexiform retinal layer.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Fibras Nervosas , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica
10.
JAMA ; 324(15): 1543-1556, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33079159

RESUMO

Importance: Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. Objective: To develop an evidence-based clinical practice guideline for adults with Down syndrome. Evidence Review: The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. Findings: From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. Conclusions and Relevance: These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.


Assuntos
Síndrome de Down/terapia , Adulto , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Comorbidade , Complicações do Diabetes/epidemiologia , Síndrome de Down/complicações , Medicina Baseada em Evidências , Humanos , Programas de Rastreamento , Obesidade/complicações
11.
Artigo em Inglês | MEDLINE | ID: mdl-33066592

RESUMO

The number of people living with dementia and Alzheimer's disease is growing rapidly, making dementia one of the biggest challenges for this century. Many studies have indicated that depression plays an important role in development of dementia, including Alzheimer's disease; depression, especially, during the late life may either increase the risk of dementia or even being its prodromal stage. Despite a notably large number of carried observational studies and/or clinical trials, the association between the late life depression and dementia remains, due to the complexity of their relationship, still unclear. Moreover, during past two decades multiple other (non-)modifiable risk and possibly protective factors such as the hypertension, social engagement, obesity, level of education or physical (in)activity have been identified and their relationship with the risk for development of dementia and Alzheimer's disease has been extensively studied. It has been proposed that to understand mechanisms of dementia and Alzheimer's disease pathogeneses require their multifactorial nature represented by these multiple factors to be considered. In this review, we first summarize the recent literature findings on roles of the late life depression and the other known (non-)modifiable risk and possibly protective factors in development of dementia and Alzheimer's disease. Then, we provide evidences supporting hypotheses that (i) depressive syndromes in late life may indicate the prodromal stage of dementia (Alzheimer's disease) and, (ii) the interplay among the multiple (non-)modifiable risk and protective factors should be considered to gain a better understanding of dementia and Alzheimer's disease pathogeneses. We also discuss the evidences of recently established interventions considered to prevent or delay the prodromes of dementia and provide the prospective future directions in prevention and treatment of dementia and Alzheimer's disease using both the single-domain and multidomain interventions.


Assuntos
Doença de Alzheimer , Demência , Depressão , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/terapia , Demência/complicações , Demência/epidemiologia , Demência/terapia , Depressão/epidemiologia , Depressão/prevenção & controle , Humanos , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco
12.
J Alzheimers Dis ; 78(2): 537-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33074240

RESUMO

We aimed to evaluate the frequency and mortality of COVID-19 in patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). We conducted an observational case series. We enrolled 204 patients, 15.2% of whom were diagnosed with COVID-19, and 41.9% of patients with the infection died. Patients with AD were older than patients with FTD (80.36±8.77 versus 72.00±8.35 years old) and had a higher prevalence of arterial hypertension (55.8% versus 26.3%). COVID-19 occurred in 7.3% of patients living at home, but 72.0% of those living at care homes. Living in care facilities and diagnosis of AD were independently associated with a higher probability of death. We found that living in care homes is the most relevant factor for an increased risk of COVID-19 infection and death, with AD patients exhibiting a higher risk than those with FTD.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/mortalidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Demência Frontotemporal/complicações , Demência Frontotemporal/mortalidade , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/complicações , Vida Independente , Masculino , Casas de Saúde , Pandemias , Prevalência , Fatores de Risco
13.
Neurology ; 95(16): e2225-e2234, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32878991

RESUMO

OBJECTIVE: To test the hypothesis that incipient Alzheimer disease (AD) may adversely affect hearing and that hearing loss may adversely affect cognition, we evaluated whether genetic variants that increase AD risk also increase problem hearing and genetic variants that increase hearing impairment risk do not influence cognition. METHODS: UK Biobank participants without dementia ≥56 years of age with Caucasian genetic ancestry completed a Digit Triplets Test of speech-in-noise hearing (n = 80,074), self-reported problem hearing and hearing with background noise (n = 244,915), and completed brief cognitive assessments. A genetic risk score for AD (AD-GRS) was calculated as a weighted sum of 23 previously identified AD-related polymorphisms. A genetic risk score for hearing (hearing-GRS) was calculated using 3 previously identified polymorphisms related to hearing impairment. Using age-, sex-, and genetic ancestry-adjusted logistic and linear regression models, we evaluated whether the AD-GRS predicted poor hearing and whether the hearing-GRS predicted worse cognition. RESULTS: Poor speech-in-noise hearing (>-5.5-dB speech reception threshold; prevalence 14%) was associated with lower cognitive scores (ß = -1.28; 95% confidence interval [CI] -1.54 to -1.03). Higher AD-GRS was significantly associated with poor speech-in-noise hearing (odds ratio [OR] 1.06; 95% CI 1.01-1.11) and self-reported problems hearing with background noise (OR 1.03; 95% CI 1.00-1.05). Hearing-GRS was not significantly associated with cognitive scores (ß = -0.05; 95% CI -0.17 to 0.07). CONCLUSIONS: Genetic risk for AD also influences speech-in-noise hearing. We failed to find evidence that genetic risk for hearing impairment affects cognition. AD disease processes or a that shared etiology may cause speech-in-noise difficulty before dementia onset.


Assuntos
Doença de Alzheimer/genética , Disfunção Cognitiva/genética , Predisposição Genética para Doença , Perda Auditiva/genética , Doença de Alzheimer/complicações , Disfunção Cognitiva/complicações , Feminino , Perda Auditiva/complicações , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Autorrelato , Percepção da Fala
14.
Ann Neurol ; 88(6): 1165-1177, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32944999

RESUMO

OBJECTIVE: Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross-sectional relationship with age, beta-amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status. METHODS: Participants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET-based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment-DS (MCI-DS), possible AD dementia, or definite AD dementia based on in-depth assessments of cognition, function, and health status. RESULTS: There were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI-DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct. INTERPRETATION: The findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity. ANN NEUROL 2020;88:1165-1177.


Assuntos
Doença de Alzheimer/patologia , Amiloide/metabolismo , Transtornos Cerebrovasculares/patologia , Síndrome de Down/patologia , Hemorragia/patologia , Hipertrofia/patologia , Infarto/patologia , Substância Branca/patologia , Doença de Alzheimer/complicações , Transtornos Cerebrovasculares/complicações , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Síndrome de Down/complicações , Feminino , Hemorragia/complicações , Humanos , Hipertrofia/complicações , Infarto/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons
15.
J Alzheimers Dis ; 78(2): 479-503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32955466

RESUMO

Alzheimer's and Parkinson's diseases (AD, PD) have a pediatric and young adult onset in Metropolitan Mexico City (MMC). The SARS-CoV-2 neurotropic RNA virus is triggering neurological complications and deep concern regarding acceleration of neuroinflammatory and neurodegenerative processes already in progress. This review, based on our MMC experience, will discuss two major issues: 1) why residents chronically exposed to air pollution are likely to be more susceptible to SARS-CoV-2 systemic and brain effects and 2) why young people with AD and PD already in progress will accelerate neurodegenerative processes. Secondary mental consequences of social distancing and isolation, fear, financial insecurity, violence, poor health support, and lack of understanding of the complex crisis are expected in MMC residents infected or free of SARS-CoV-2. MMC residents with pre-SARS-CoV-2 accumulation of misfolded proteins diagnostic of AD and PD and metal-rich, magnetic nanoparticles damaging key neural organelles are an ideal host for neurotropic SARS-CoV-2 RNA virus invading the body through the same portals damaged by nanoparticles: nasal olfactory epithelium, the gastrointestinal tract, and the alveolar-capillary portal. We urgently need MMC multicenter retrospective-prospective neurological and psychiatric population follow-up and intervention strategies in place in case of acceleration of neurodegenerative processes, increased risk of suicide, and mental disease worsening. Identification of vulnerable populations and continuous effort to lower air pollution ought to be critical steps.


Assuntos
Doença de Alzheimer/complicações , Encefalopatias/etiologia , Infecções por Coronavirus/complicações , Poluentes Ambientais/efeitos adversos , Nanopartículas/efeitos adversos , Doença de Parkinson/complicações , Pneumonia Viral/complicações , Adulto , Poluição do Ar/efeitos adversos , Doença de Alzheimer/fisiopatologia , Progressão da Doença , Humanos , Pessoa de Meia-Idade , Pandemias , Doença de Parkinson/fisiopatologia , Suicídio/estatística & dados numéricos , População Urbana
16.
Yonsei Med J ; 61(8): 731-735, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734738

RESUMO

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently established neurodegenerative disease entity. LATE neuropathological change (LATE-NC) is characterized by a TDP-43 proteinopathy that mainly involves the amygdala and medial temporal structures, with or without hippocampal sclerosis. LATE-NC is typically observed in individuals aged 80 years or older and manifests clinically as amnestic memory decline. Herein, we report a case of LATE diagnosed by brain autopsy in an 82-year-old male who had an 11-year history of memory impairment. Pathological examination revealed high Alzheimer disease neuropathological changes, as well as amygdala-predominant Lewy body pathology. In addition, immunohistochemistry for TDP-43 revealed neuronal and glial cytoplasmic inclusions in the dentate gyrus of the hippocampus, amygdala, and inferior temporal cortex. Increasing awareness of the newly defined entity LATE will enhance our understanding of the neurodegenerative processes that occur in the oldest individuals.


Assuntos
Autopsia , Sistema Límbico/patologia , Proteinopatias TDP-43/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Comorbidade , Humanos , Masculino , Tomografia Computadorizada por Raios X
17.
Neurology ; 95(12): e1640-e1649, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32759190

RESUMO

OBJECTIVE: To examine whether neuropathologic burden is associated with hearing impairment. METHODS: We studied 2,755 autopsied participants ≥55 years of age from the National Alzheimer's Coordinating Center database. Participants had at least 1 clinical evaluation at US National Institute on Aging-funded Alzheimer's Disease Center no more than 2 years before death. Patients were classified as hearing impaired by clinician report at baseline. Common dementia neuropathologies included Alzheimer disease pathologic change (Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque density, neurofibrillary degeneration Braak stage), Lewy body disease, gross infarcts, and microinfarcts. Logistic regression models predicted impaired hearing with adjustment for age at death, sex, race, education, center, and follow-up time. Relative risks were calculated with the use of marginal standardization. RESULTS: Impaired hearing was common (32%). In participants who were cognitively normal at baseline (n = 580), impaired hearing was associated with higher Braak stage (relative risk [RR] 1.33 per 2-stage increase, 95% confidence interval [CI] 1.06-1.66) but not other pathologies. In participants with dementia (n = 2,175), impaired hearing was positively associated with microinfarcts (RR 1.18, 95% CI 1.00-1.39) and inversely associated with neuritic plaque density (RR 0.91 per score increase, 95% CI 0.85-0.99). Development of impaired hearing in those with cognitive impairment was associated with neocortical Lewy bodies (1.26, 95% CI 1.02-1.55). CONCLUSIONS: Impaired hearing, reported before the onset of cognitive impairment, was associated with increased neurofibrillary tangle burden. Impaired hearing in those with cognitive impairment was associated with microinfarcts and neocortical Lewy bodies but not typical Alzheimer disease pathologic change. Functional hearing problems may be a preclinical marker of neurofibrillary neurodegeneration, although replication is needed.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Perda Auditiva/patologia , Placa Amiloide/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Autopsia , Feminino , Perda Auditiva/complicações , Humanos , Corpos de Lewy/patologia , Masculino , Emaranhados Neurofibrilares/patologia
18.
Neurology ; 95(14): e1951-e1962, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32753441

RESUMO

OBJECTIVE: To examine the impact of 3 pathologic groups, pure limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy (LATE) neuropathologic changes (NC), pure Alzheimer disease neuropathologic change (ADNC), and mixed ADNC with LATE-NC, on late-life cognitive decline. METHODS: Data came from 1,356 community-based older persons who completed detailed annual cognitive testing and systematic neuropathologic examination at autopsy to identify LATE-NC, ADNC, and other age-related pathologies. Persons were categorized into (0) a group without a pathologic diagnosis of LATE or ADNC (n = 378), (1) LATE-NC without ADNC (n = 91), (2) ADNC without LATE-NC (n = 535), and (3) mixed ADNC with LATE-NC (n = 352). We used mixed-effect models to examine the group associations with rate of decline in global cognition and 5 cognitive domains and then examined whether age modified associations. RESULTS: Compared to those without LATE-NC or ADNC, those with pure LATE-NC had a faster decline in global cognition (p = 0.025) and episodic memory (p = 0.002); however, compared to persons with pure ADNC, those with pure LATE-NC showed a slower decline. Those with mixed ADNC with LATE-NC showed the fastest decline compared to those with either pathology alone. Persons ≥90 years of age with mixed ADNC with LATE-NC had slower cognitive decline compared to those ≤89 years of age. CONCLUSION: Persons with pure LATE-NC follow a slower trajectory compared to those with pure ADNC. Those with mixed LATE/ADNC have a steeper decline than individuals with either pathology alone. In addition, age may modify the effect of pathology on cognitive decline. These findings have important implications for the development of biomarkers and prognosis for late-life cognitive decline. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that LATE-NC and Alzheimer disease pathologic changes are associated with different trajectories of late-life cognitive decline.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Proteinopatias TDP-43/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Disfunção Cognitiva/etiologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Proteinopatias TDP-43/complicações
19.
Ann Neurol ; 88(6): 1065-1076, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32799383

RESUMO

OBJECTIVE: The longitudinal association of the blood biomarkers total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) with common sporadic Alzheimer disease (AD) and cognitive decline is not established. METHODS: Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of t-tau, Nf-L, and GFAP were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, had completed in-home cognitive assessments, and had undergone 1.5T structural magnetic resonance imaging. RESULTS: Higher concentrations of serum biomarkers were associated with the development of clinical AD; especially, the time-specific associations were notable: t-tau 8 to 16 years, and Nf-L and GFAP 4 to 8 years prior to clinical AD. Serum biomarkers were associated with faster cognitive decline over 16 years; baseline t-tau > 0.40pg/ml had 30% faster decline, Nf-L > 25.5pg/ml had 110% faster decline, and GFAP > 232pg/ml had 130% faster decline compared to those in the lowest quartile. Participants with baseline GFAP > 232pg/ml showed 160% faster decline in hippocampal volume compared to those with values < 160pg/ml. Additionally, higher baseline t-tau was associated with faster increase in 3rd ventricular volume, and baseline Nf-L and GFAP were associated with faster decline in cortical thickness. INTERPRETATION: Serum t-tau, Nf-L, and GFAP predict the development of sporadic AD and cognitive decline, and changes in structural brain characteristics, suggesting their usefulness not only as screening and predictive biomarkers, but also in capturing the pathogenesis of Alzheimer dementia. ANN NEUROL 2020;88:1065-1076.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Proteína Glial Fibrilar Ácida/sangue , Proteínas de Neurofilamentos/sangue , Proteínas tau/sangue , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Biomarcadores/sangue , Córtex Cerebral/patologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/patologia , Diagnóstico Precoce , Feminino , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Valor Preditivo dos Testes
20.
J Alzheimers Dis ; 77(1): 67-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804094

RESUMO

BACKGROUND: Facing the novel coronavirus disease 2019 (COVID-19), most vulnerable individuals are seniors, especially those with comorbidities. More attention needs to been paid to the COVID-19 patients with Alzheimer's disease (AD), which is the top age-related neurodegenerative disease. OBJECTIVE: Since it is unclear whether AD patients are prone to COVID-19 infection and progression to severe stages, we report for the first time a retrospective analysis of the clinical characteristics of AD patients with COVID-19 pneumonia. METHODS: We conducted a retrospective cohort study of the clinical data of 19 AD patients with COVID-19 pneumonia, compared with 23 non-AD COVID-19 patients admitted at the same time to our hospital. Demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS: Between AD patients and non-AD patients with COVID-19 pneumonia, the pneumonia severity was not significantly different. AD patients had a higher clustering onset than non-AD patients. The median duration from symptom onset to hospitalization were shorter in AD patients than non-AD patients, indicating the former were sent to the hospital by their family or from nursing home earlier than the later. The median duration from hospitalization to discharge seemed shorter in AD patients than non-AD patients. Dementia patients seemed less likely to report fatigue. It is noticed that more AD patients might have pericardial effusion than the non-AD patients. CONCLUSION: AD patients with COVID-19 were in milder conditions with a better prognosis than non-AD patients. AD patients who had adequate access to healthcare showed resilience to COVID-19 with shorter hospital stays.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/psicologia , Pneumonia Viral/complicações , Pneumonia Viral/psicologia , Resiliência Psicológica , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Estudos de Coortes , Progressão da Doença , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente/estatística & dados numéricos , Derrame Pleural/epidemiologia , Derrame Pleural/etiologia , Pneumonia/complicações , Pneumonia/terapia , Prognóstico
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