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OBJECTIVE: Research suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood in response to neuroaxonal damage, and they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic nonepileptic seizures (PNES) and other nonepileptic disorders. METHODS: We recruited consecutive adults admitted for video-electroencephalographic monitoring and formal neuropsychiatric assessment. NfL and GFAP levels were quantified and compared between different patient groups and an age-matched reference cohort (n = 1926) and correlated with clinical variables in patients with epilepsy. RESULTS: A total of 138 patients were included, of whom 104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p = .04, GFAP p = .04). A high proportion of patients with epilepsy (20%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%). NfL levels above the 95th percentile of the reference cohort had a 95% positive predictive value for epilepsy. Patients with epilepsy who had NfL levels above the 95th percentile were younger than those with lower levels (37.5 vs. 43.8 years, p = .03). SIGNIFICANCE: An elevated NfL or GFAP level in an individual patient may support an underlying epilepsy diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.
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BACKGROUND AND OBJECTIVES: Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD. METHODS: MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305). RESULTS: The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified. DISCUSSION: We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.
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Doença de Alzheimer , Astrócitos , Biomarcadores , Proteína 1 Semelhante à Quitinase-3 , Proteína Glial Fibrilar Ácida , Subunidade beta da Proteína Ligante de Cálcio S100 , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Humanos , Biomarcadores/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína Glial Fibrilar Ácida/sangue , Astrócitos/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnósticoRESUMO
BACKGROUND: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. METHODS: This was a double-blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in-hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3-point reduction in the MDAS. RESULTS: One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p-value 0.42, a non-significant difference. A post-hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p-value = 0.033, Wilcoxon Rank Sum test). CONCLUSIONS: This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied.
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Delírio , Melatonina , Humanos , Melatonina/uso terapêutico , Melatonina/administração & dosagem , Masculino , Feminino , Método Duplo-Cego , Delírio/tratamento farmacológico , Idoso , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais , Hospitalização , Resultado do TratamentoRESUMO
Late-onset Alzheimer's disease is the leading cause of dementia worldwide, accounting for a growing burden of morbidity and mortality. Diagnosing Alzheimer's disease before symptoms are established is clinically challenging, but would provide therapeutic windows for disease-modifying interventions. Blood biomarkers, including genetics, proteins and metabolites, are emerging as powerful predictors of Alzheimer's disease at various timepoints within the disease course, including at the preclinical stage. In this review, we discuss recent advances in such blood biomarkers for determining disease risk. We highlight how leveraging polygenic risk scores, based on genome-wide association studies, can help stratify individuals along their risk profile. We summarize studies analyzing protein biomarkers, as well as report on recent proteomic- and metabolomic-based prediction models. Finally, we discuss how a combination of multi-omic blood biomarkers can potentially be used in memory clinics for diagnosis and to assess the dynamic risk an individual has for developing Alzheimer's disease dementia.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Multiômica , Proteômica , BiomarcadoresRESUMO
INTRODUCTION: Dementia is an emergent health priority for Indigenous peoples worldwide, yet little is known about disease drivers and protective factors. METHODS: Database searches were conducted in March 2022 to identify original publications on risk, protective, genetic, neuroradiological, and biological factors related to dementia and cognitive impairment involving Indigenous peoples. RESULTS: Modifiable risk factors featured across multiple studies include childhood adversity, hearing loss, low education attainment, unskilled work history, stroke, head injury, epilepsy, diabetes, hypertension, hyperlipidemia, depression, low BMI, poor mobility, and continence issues. Non-modifiable risk factors included increasing age, sex, and genetic polymorphisms. Education, ex-smoking, physical and social activity, and engagement with cultural or religious practices were highlighted as potential protective factors. There is a paucity of research on dementia biomarkers involving Indigenous peoples. DISCUSSION: Greater understanding of modifiable factors and biomarkers of dementia can assist in strength-based models to promote healthy ageing and cognition for Indigenous peoples.
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Demência , Povos Indígenas , Humanos , Fatores de Risco , Escolaridade , Biomarcadores , Demência/epidemiologiaRESUMO
OBJECTIVE: Neurofibrillary tangles are present in a proportion of people with dementia with Lewy bodies and may be associated with worse cognition. Recent advances in biomarkers for Alzheimer's disease include second-generation tau positron emission tomography as well as the detection of phosphorylated tau at threonine 181 (p-tau181) in plasma. This study aimed to investigate tau in people with dementia with Lewy bodies using a second-generation tau positron emission tomography tracer as well as plasma p-tau181. METHODS: Twenty-seven participants (mean age 74.7 ± 5.5) with clinically diagnosed probable dementia with Lewy bodies underwent comprehensive clinical assessment and positron emission tomography imaging (18F-MK6240 and 18F-NAV4694). Plasma p-tau181 levels were measured using Simoa technology. RESULTS: Five dementia with Lewy bodies participants (18.5%) had an abnormal tau positron emission tomography (increased tau uptake in the temporal meta-region-of-interest). Higher plasma p-tau181 concentrations correlated with higher tau deposition in the temporal region (ρ = 0.46, 95% confidence interval = [0.10, 0.72]) and classified abnormal tau positron emission tomography in dementia with Lewy bodies with an area under the curve of 0.95 (95% confidence interval = [0.86, 0.99]). Plasma p-tau181 also correlated positively with cortical amyloid-beta binding (ρ = 0.68, 95% confidence interval = [0.40, 0.84]) and classified abnormal amyloid-beta positron emission tomography in dementia with Lewy bodies with an area under the curve of 0.91 (95% confidence interval = [0.79, 0.99]). There was no association found between tau deposition and any of the clinical variables. CONCLUSIONS: Tau is a common co-pathology in dementia with Lewy bodies. Plasma p-tau181 correlated with abnormal tau and amyloid-beta positron emission tomography and may potentially be used as a marker to identify co-morbid Alzheimer's disease-related pathology in dementia with Lewy bodies. The clinical implications of tau in dementia with Lewy bodies need to be further evaluated in larger longitudinal studies.
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Doença de Alzheimer , Doença por Corpos de Lewy , Idoso , Idoso de 80 Anos ou mais , Humanos , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Doença por Corpos de Lewy/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Proteínas tau/metabolismoRESUMO
Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of CMB in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), using meta-analytic methods. Sixty-five MRI studies were included after a systematic search on major electronic databases. We found that the prevalence of CMB was comparable across the three dementia subtypes (31-36%) and was highly influenced by the MRI techniques used. CMB in AD were associated with a history of hypertension and amyloid-ß burden. In contrast, CMB in DLB, despite being predominantly lobar, were associated with hypertension, but not amyloid-ß burden. These findings suggest that the underlying pathophysiology of CMB in DLB might differ from that of AD. There was substantially larger number of AD studies identified and more studies evaluating CMB in Lewy body dementias are warranted.
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Doença de Alzheimer , Demência , Hipertensão , Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/complicações , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/epidemiologia , Demência/epidemiologia , Demência/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Prevalência , Peptídeos beta-Amiloides , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/complicações , Hipertensão/complicaçõesRESUMO
Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson's disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.
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Demência , Doença por Corpos de Lewy , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença por Corpos de Lewy/patologia , Estudos Transversais , Doença de Parkinson/líquido cefalorraquidiano , Inflamação , alfa-Sinucleína/líquido cefalorraquidianoRESUMO
INTRODUCTION: Degeneration of cortical cholinergic projections from the nucleus basalis of Meynert (NBM) is characteristic of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), whereas involvement of cholinergic projections from the pedunculopontine nucleus (PPN) to the thalamus is less clear. METHODS: We studied both cholinergic projection systems using a free water-corrected diffusion tensor imaging (DTI) model in the following cases: 46 AD, 48 DLB, 35 mild cognitive impairment (MCI) with AD, 38 MCI with Lewy bodies, and 71 controls. RESULTS: Free water in the NBM-cortical pathway was increased in both dementia and MCI groups compared to controls and associated with cognition. Free water along the PPN-thalamus tract was increased only in DLB and related to visual hallucinations. Results were largely replicated in an independent cohort. DISCUSSION: While NBM-cortical projections degenerate early in AD and DLB, the thalamic cholinergic input from the PPN appears to be more selectively affected in DLB and might associate with visual hallucinations. HIGHLIGHTS: Free water in the NBM-cortical cholinergic pathways is increased in AD and DLB. NBM-cortical pathway integrity is related to overall cognitive performance. Free water in the PPN-thalamus cholinergic pathway is only increased in DLB, not AD. PPN-thalamus pathway integrity might be related to visual hallucinations in DLB.
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Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/metabolismo , Doença por Corpos de Lewy/diagnóstico por imagem , Imagem de Tensor de Difusão , Alucinações/complicações , Colinérgicos , ÁguaRESUMO
Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid-beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or co-exist with intraparenchymal neurodegenerative proteinopathies, which makes it an increasingly relevant condition for adult physicians in all areas of medical practice. The vast majority of cases of CAA are sporadic with a small minority of familial cases. CAA is asymptomatic in many older adults but increases the risk of fatal intracerebral or subarachnoid haemorrhage. We review the existing literature on CAA and summarise the key findings. We specifically explore clinical challenges relevant to CAA, particularly in diagnosis, management of intracranial haemorrhage and management of concurrent medical conditions.
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Angiopatia Amiloide Cerebral , Hemorragia Subaracnóidea , Humanos , Idoso , Austrália/epidemiologia , Angiopatia Amiloide Cerebral/diagnóstico , Angiopatia Amiloide Cerebral/epidemiologia , Angiopatia Amiloide Cerebral/terapia , Hemorragias Intracranianas/complicações , Incidência , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Amyloid-beta often co-exists in dementia with Lewy bodies, but its clinical relevance in dementia with Lewy bodies remains unclear. This study aimed to investigate the clinical and imaging correlates of amyloid-beta deposition in dementia with Lewy bodies, particularly its relationship with cortical thickness in Alzheimer's disease-prone regions and hippocampal volume. METHODS: Twenty-four participants with probable dementia with Lewy bodies underwent high-resolution magnetic resonance imaging and amyloid-beta positron emission tomography imaging using the radiotracer 18F-NAV4694. Amyloid-beta deposition was quantified and reported using the Centiloid method. RESULTS: Amyloid-beta positivity, defined as Centiloid > 50, was present in 45.8% of dementia with Lewy bodies participants. There were no statistically significant differences in clinical characteristics between Aß+ and Aß- dementia with Lewy bodies. Compared with the Aß- group, Aß+ dementia with Lewy bodies exhibited greater global cortical thinning as well as in the Alzheimer's disease-prone region of interest, adjusted for age, sex and years of education. A mean cortical thickness of 5.12 mm across a combined meta-region of interest has a sensitivity of 88.9% and specificity of 90.0% in discriminating Aß+ from Aß- dementia with Lewy bodies. Hippocampal volume was not different between groups. CONCLUSION: Early structural changes in cortical thickness, but not hippocampal volume, were observed in dementia with Lewy bodies with significant amyloid-beta burden. This may represent an early Alzheimer's disease-related neurodegenerative process.
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Doença de Alzheimer , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologia , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologiaRESUMO
INTRODUCTION: Cerebral microbleeds (CMB) are associated with cognitive impairment and hypertensive or cerebral amyloid angiopathy. The pathophysiology and clinical significance of CMB in dementia with Lewy bodies (DLB) are not well understood. Our study aimed to investigate the prevalence of CMB in DLB and to estimate the magnitudes of their clinical associations. METHODS: Twenty participants with DLB (mean age 74 ± 5 years) were included in this cross-sectional study. All participants underwent 3 T magnetic resonance imaging. CMB number and location were assessed on susceptibility-weighted imaging or quantitative susceptibility mapping. Amyloid-beta (Aß) positron emission tomography (PET) scans were also performed. Between-group comparisons were estimated using risk ratios (RR) for categorical variables, and mean differences or median regression coefficients for continuous variables. RESULTS: CMB were present in 30% of the DLB participants, with a lobar predominance observed. DLB with CMB were more likely to be on antithrombotic therapy (100%), compared to those without CMB (43%; RR 2.33 [95% CI 1.27, 4.27]). Those with CMB were also more likely to report a history of hypertension (100%) compared to those without (70%; RR 1.75 [95% CI 1.11, 2.75]). DLB core clinical features, cognition and functional status did not differ between the two groups. There was no association found between the presence of CMB and cortical Aß deposition on PET imaging. CONCLUSION: CMB are not uncommon in DLB and may be associated with hypertensive small vessel disease. Further studies into the pathophysiology and clinical implications of CMB in DLB are needed.
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Angiopatia Amiloide Cerebral , Doença por Corpos de Lewy , Humanos , Idoso , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico por imagem , Estudos Transversais , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Peptídeos beta-Amiloides , Imageamento por Ressonância Magnética , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologiaRESUMO
Less than 50 years since tau was first isolated from a porcine brain, its detection in femtolitre concentrations in biological fluids is revolutionizing the diagnosis of neurodegenerative diseases. This review highlights the molecular and technological advances that have catapulted tau from obscurity to the forefront of biomarker diagnostics. Comprehensive updates are provided describing the burgeoning clinical applications of tau as a biomarker of neurodegeneration. For the clinician, tau not only enhances diagnostic accuracy, but holds promise as a predictor of clinical progression, phenotype, and response to drug therapy. For patients living with neurodegenerative disorders, characterization of tau dysregulation could provide much-needed clarity to a notoriously murky diagnostic landscape.
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Doença de Alzheimer , Proteínas tau , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Animais , Biomarcadores , Encéfalo/metabolismo , Suínos , Proteínas tau/metabolismoRESUMO
BACKGROUND: Recent reports raise the possibility of cerebral amyloid angiopathy (CAA) leading to intracerebral hemorrhage in young adults following childhood neurosurgery, suggesting transmission of amyloid-ß (Aß) through neurosurgical procedures including dura mater grafting. Parenchymal Aß deposition, and to a lesser extent tau aggregation, similar to that seen in Alzheimer disease, have also been described. METHODS: We conducted a database review of 634 consecutive intracerebral hemorrhage patients aged <65 years at a tertiary stroke center over 20 years to identify such patients. RESULTS: We identified 3 patients aged in their thirties who presented with spontaneous lobar intracerebral hemorrhage, with imaging or neuropathology consistent with CAA, and a history of childhood neurosurgery. Two of these patients had undergone a dural repair using cadaveric dura mater (Lyodura). In addition to CAA, both patients had neuropathologically confirmed parenchymal Aß and tau deposits, characteristic of Alzheimer disease. CONCLUSIONS: Our findings support the concept of neurosurgical Aß transmission but suggest that such cases are rare in standard clinical practice.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Neurocirurgia , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/cirurgia , Humanos , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
BACKGROUND: Guidelines highlight the importance of an individualized approach to treatment initiation for Parkinson's disease. Our aim was to investigate initiation of anti-Parkinson medication in Australia from 2013-2018, and to determine factors predicting choice of initial treatment. METHODS: Cohort of new-users (N = 4,887) of anti-Parkinson medication aged ≥ 40 years were identified from a 10% random representative sample of national medication dispensing data from July-2013 to June-2018. Changes in treatment initiation were examined across the whole cohort and stratified by age and sex. RESULTS: Treatment initiation was most frequent with levodopa followed by non-ergot dopamine agonists (DAs) and anticholinergics. Two thirds initiated with levodopa across the study period. Initiation with non-ergot DAs increased from 22 to 27% (rate ratio, RR 1.23, 95% confidence interval, CI 1.02-1.47) and initiation with anticholinergics decreased from 6.9% to 2.4% (RR 0.34, 95% CI 0.21-0.55) from 2013-2018. Among persons aged ≥ 65 years, one third of women and one fourth of men initiated on levodopa. Among women aged < 65 years, rates of treatment initiation with DAs (37%) and levodopa (37%) were similar in 2013/2014 but initiation with DA exceeded levodopa thereafter. Among men aged < 65 years, treatment initiation with levodopa (44%-49%) remained more frequent than initiation with DAs (29%-32%) throughout the study period. CONCLUSIONS: Treatment initiation with levodopa was most frequent among persons aged ≥ 65 years, consistent with current guidelines. Whilst the value of levodopa sparing strategies is unclear, treatment initiation with DA has become increasingly common relative to levodopa among women but not among men aged < 65 years.
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Levodopa , Doença de Parkinson , Adulto , Idoso , Antiparkinsonianos/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologiaRESUMO
BACKGROUND: Midlife cardiovascular risk factors (CVRF) are associated with reduced cognition and an increased risk of dementia. OBJECTIVE: To further investigate this association using remote unsupervised online assessment of cognition and cardiovascular risk in middle-aged adults; and to explore the extent to which the association is altered by carriage of the APOE É4 allele. METHODS: The Healthy Brain Project is an online cohort of middle-aged cognitively unimpaired adults (40-70 years) who have undergone cognitive assessment and provided self-reports of demographic and health history. Cardiovascular risk was determined by ascertaining history of hypertension, hypercholesterolemia, diabetes mellitus, overweight (body mass index≥25), and current cigarette smoking. Participants (nâ=â2,480) were then grouped based on the number of reported CVRF into no CVRF, 1, 2, and≥3 CVRF. Associations between the number of CVRF as a continuous variable, CVRF group, and each individual CVRF with composite measures of attention, memory and subjective cognitive function were investigated. RESULTS: Higher number of CVRF was associated with poorer attention (ß=â-0.042, pâ=â0.039) and memory (ß=â-0.080, pâ<â0.001), but not with subjective cognitive function. When considered individually, current smoking (ß=â-0.400, pâ=â0.015), diabetes (ß=â-0.251, pâ=â0.023), and hypercholesterolemia (ß=â-0.109, pâ=â0.044) were independently associated with poorer memory performance. APOE É4 carriers with≥1 CVRF performed worse on memory than É4 carriers with no CVRFs (ß(SE)â=â0.259(0.077), pâ=â0.004). This was not observed in É4 non-carriers. CONCLUSION: In cognitively normal middle-aged adults, CVRF were associated with poorer cognition, particularly in the memory domain. These results support feasibility of online assessment of cardiovascular risk for cognitive impairment.
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Doenças Cardiovasculares , Diabetes Mellitus , Hipercolesterolemia , Hiperlipidemias , Apolipoproteínas E , Encéfalo , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Hipercolesterolemia/epidemiologia , Transtornos da Memória , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
INTRODUCTION: Many patients with cognitive and neuropsychiatric symptoms face diagnostic delay and misdiagnosis. We investigated whether cerebrospinal fluid (CSF) neurofilament light (NfL) and total-tau (t-tau) could assist in the clinical scenario of differentiating neurodegenerative (ND) from psychiatric disorders (PSY), and rapidly progressive disorders. METHODS: Biomarkers were examined in patients from specialist services (ND and PSY) and a national Creutzfeldt-Jakob registry (Creutzfeldt-Jakob disease [CJD] and rapidly progressive dementias/atypically rapid variants of common ND, RapidND). RESULTS: A total of 498 participants were included: 197 ND, 67 PSY, 161 CJD, 48 RapidND, and 20 controls. NfL was elevated in ND compared to PSY and controls, with highest levels in CJD and RapidND. NfL distinguished ND from PSY with 95%/78% positive/negative predictive value, 92%/87% sensitivity/specificity, 91% accuracy. NfL outperformed t-tau in most real-life clinical diagnostic dilemma scenarios, except distinguishing CJD from RapidND. DISCUSSION: We demonstrated strong generalizable evidence for the diagnostic utility of CSF NfL in differentiating ND from psychiatric disorders, with high accuracy.
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Doença de Alzheimer , Síndrome de Creutzfeldt-Jakob , Transtornos Mentais , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Diagnóstico Tardio , Filamentos Intermediários , Proteínas tau/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidianoRESUMO
BACKGROUND AND PURPOSE: Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications. METHODS: A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage. RESULTS: Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age-matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%-48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD. CONCLUSION: The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes.
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Doença de Alzheimer , Transtornos Cerebrovasculares , Demência , Doença por Corpos de Lewy , Doença de Parkinson , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/epidemiologia , Demência/epidemiologia , Demência/etiologia , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/epidemiologia , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/patologiaRESUMO
The burden of dementia will increase as the Australian population ages and grows in coming decades. Early and accurate diagnosis remains challenging, and disproportionately so for particular groups, including rural communities. Recent advances in technology, however, now allow reliable measurement of blood biomarkers that could improve diagnosis in a range of settings. We discuss the most promising biomarker candidates for translation into clinical practice and research in the near future.