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PURPOSE OF THE STUDY: Posterior cortical atrophy is a clinico-radiographical syndrome that presents with higher-order visual dysfunction and is most commonly due to Alzheimer's disease. Understanding factors associated with atypical presentations of Alzheimer's disease, such as posterior cortical atrophy (PCA), holds promise to shape our understanding of AD pathophysiology. Thus, we aimed to compare MRI evidence of lobar microbleeds (LMBs) in posterior cortical atrophy (PCA) syndrome to typical AD (tAD) and to assess and compare MRI evidence of cerebral amyloid angiopathy (CAA) in each group. FINDINGS: We retrospectively collected clinical and MRI data from participants with PCA (n = 26), identified from an institutional PCA registry, and participants with tAD (n = 46) identified from electronic health records from a single institution. LMBs were identified on susceptibility-weighted imaging (SWI); the Fazekas grade of white matter disease was assessed using FLAIR images, and Boston criteria version 2.0 for cerebral amyloid angiopathy were applied to all data. The proportion of participants with PCA and LMB (7.7%) was lower than for tAD (47.8%) (p = 0.005). The frequency of "probable" CAA was similar in both groups, while "possible" CAA was more frequent in tAD (30.4%) than PCA (0%) (p = 0.001). The Fazekas grades were not different between groups. Lobar microbleeds on SWI were not more common in PCA than in typical AD. Clinicopathological investigations are necessary to confirm these findings. The factors that contribute to the posterior cortical atrophy phenotype are unknown.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Estudos Retrospectivos , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Atrofia/complicaçõesRESUMO
Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.
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Neurologia , Humanos , Neurologia/tendências , Neuropsiquiatria/tendênciasRESUMO
OBJECTIVE: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. METHODS: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. RESULTS: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). INTERPRETATION: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217-224.
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Rede Nervosa/fisiopatologia , Inconsciência/psicologia , Percepção Visual , Adulto , Idoso , Mapeamento Encefálico , Conectoma , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Pulvinar/diagnóstico por imagem , Pulvinar/fisiopatologia , Descanso , Transtornos da Visão , Campos Visuais , Adulto JovemRESUMO
BACKGROUND: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. METHODS: We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). RESULTS: When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aß42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. DISCUSSION: This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.
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Doença de Alzheimer , Substância Branca , Animais , Humanos , Feminino , Idoso , Neuritos/patologia , Imagem de Tensor de Difusão/métodos , Gliose/patologia , Encéfalo/patologia , Neuroimagem/métodos , Doença de Alzheimer/patologia , Substância Branca/patologia , Imagem de Difusão por Ressonância MagnéticaRESUMO
PURPOSE OF REVIEW: This review is intended to assist the reader in gaining the knowledge and skills necessary for the recognition and assessment of higher-order visual dysfunction due to neurodegenerative diseases including Alzheimer's disease, dementia with Lewy bodies, Parkinson's dementia, corticobasal degeneration, Creutzfeldt-Jakob disease, and the posterior cortical atrophy syndrome. Clinical problem-solving and pattern recognition must be developed and practiced to accurately diagnosis disturbances of higher-order visual function, and knowledge of higher-order visual brain regions and their visual syndromes forms the foundation for deciphering symptoms presented by patients and/or their care partners. Tests of higher-order visual dysfunction must be assembled by the clinician and assessment can take time and effort. The use of screening tests, follow-up visits, and formal neuropsychological referrals are critical components for accurate diagnosis and these principles are reviewed here. RECENT FINDINGS: A recent survey of neuro-ophthalmologists revealed that over half of the respondents report that 5-10% of their new patient referrals carry a diagnosis of neurodegenerative disease and many patients were referred for visual symptoms of unknown cause. Despite over a century of discovery related to higher-order visual functions of the human brain, translation of discovery to the clinical assessment of patients has been slow or absent. As with the approach to translational medicine in general, to see meaningful progress, an interdisciplinary approach is indispensable. The first step involves the application of discoveries from the field visual neuroscience by clinicians from the fields of ophthalmology, neurology, and neuropsychology, and from the disciplines of neuro-ophthalmology and behavioral neurology. The unmet need for recognition, assessment, and management of higher-order visual dysfunction in neurodegeneration is evident and clinicians can contribute to closing the gap by using the approach and the tools outlined in the review.
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Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/complicações , Encéfalo , Humanos , Corpos de Lewy , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/diagnóstico , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologiaRESUMO
PURPOSE OF REVIEW: To provide perspectives on the importance of understanding longitudinal profiles of posterior cortical atrophy (PCA) and report results of a scoping review to identify data and knowledge gaps related to PCA survival and longitudinal clinical and biomarker outcomes. RECENT FINDINGS: Thirteen longitudinal studies were identified; all but two had fewer than 30 participants with PCA. Relatively few longitudinal data exist, particularly for survival. In PCA, posterior cortical dysfunction and atrophy progress at faster rates compared to non-posterior regions, potentially up to a decade after symptom onset. Unlike typical AD, PCA phenotype-defined cognitive dysfunction and atrophy remain relatively more severe compared to other regions throughout the PCA course. Select cognitive tests hold promise as PCA outcome measures and for staging. Further longitudinal investigations are critically needed to enable PCA inclusion in treatment trials and to provide appropriate care to patients and enhance our understanding of the pathophysiology of dementing diseases.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Atrofia/patologia , Disfunção Cognitiva/patologia , Testes Neuropsicológicos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologiaRESUMO
BACKGROUND: Unrecognized neurodegenerative diseases (NDD) in age-related eye disease research studies have the potential to confound vision-specific quality of life and retinal optical coherence tomography (OCT) outcome measures. The aim of this exploratory study was to investigate relationships between NDD screening tools and visual outcome measures in a small cohort of controls from the Colorado Age-Related Macular Degeneration Registry (CO-AMD), to consider the utility of future studies. METHODS: Twenty-nine controls from the CO-AMD were screened using the Montreal Cognitive Assessment (MoCA), a Colorado Parkinsonian Checklist, and the Lewy Body Composite Risk Score. Univariate and multivariable linear regression modeling was used to assess associations between screening tools and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and macular OCT outcome measures, and t tests were used to evaluate outcome measure differences between those with normal vs abnormal MoCA scores. RESULTS: One patient withdrew. The average age was 72.8 years, and 68% were female patients. Ten participants (36%) had abnormal MoCA scores, and their VFQ-25 scores were only 1 point less and not statistically different than those with normal MoCA scores. Macular OCT volumes and thicknesses for retinal nerve fiber layer (RNFL) and retinal ganglion cell layer were consistently and moderately lower for those with abnormal MoCA scores, and a positive association between MoCA and macular RNFL volume was observed, although differences and regression were not significant. Parkinson screening tests were abnormal for only 4 participants and were not associated with OCT or VFQ-25 measures by regression modeling. CONCLUSIONS: Given the degree and direction of observed differences, further investigation is warranted regarding the relationship between cognitive screening tools and macular OCT measures in age-related eye disease research, but future investigations regarding the relationship between NDD screening tools and VFQ-25 seem unwarranted.
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Degeneração Macular , Doenças Neurodegenerativas , Idoso , Feminino , Humanos , Degeneração Macular/diagnóstico , Masculino , Qualidade de Vida/psicologia , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
BACKGROUND AND PURPOSE: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. METHODS: We identified three individuals with PRES due to COVID-19 in our hospital system. One patient was identified on presentation to our neuro-ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID-19 identified through systematic literature search of PubMed/LitCOVID. RESULTS: All three patients were hospitalized with severe COVID-19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID-19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication. CONCLUSIONS: As we learn about enduring neurological complications of COVID-19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID-19.
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COVID-19 , Síndrome da Leucoencefalopatia Posterior , Cuidados Críticos , Humanos , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , SARS-CoV-2 , Transtornos da Visão/etiologiaRESUMO
BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder characterized by ataxia, tremor, and parkinsonism. Eye motility abnormalities on the clinical examination of FXTAS patients have not been formally studied. METHODS: A case-control study with fragile X gene mutation carriers with and without FXTAS and normal controls was conducted and included a videotaping of ocular items of the International Cooperative Ataxia Rating Scale (ICARS). A neuro-ophthalmologist blinded to gene status rated nystagmus, ocular pursuit, and saccades. RESULTS: Forty-four cases and controls were recruited, with an average age of 55.2 years (±7.4) and 57% women. Gaze-evoked nystagmus was increased in fragile X gene carriers (odds ratio 1.44, 95% confidence interval: 0.33-7.36) but was not statistically significant. There was no difference in ocular pursuit nor saccade dysmetria between cases and controls. CONCLUSION: The results show that clinical examination findings of ocular abnormalities, using the ICARS oculomotor disorders movement subscale, are not more common in FXTAS or FMR1 premutation carriers than normal controls on examination in the clinic. Examining a larger cohort of patients with FXTAS would be an ideal next step.
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Síndrome do Cromossomo X Frágil , Tremor , Ataxia/complicações , Ataxia/diagnóstico , Ataxia/genética , Estudos de Casos e Controles , Movimentos Oculares , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Humanos , Masculino , Pessoa de Meia-Idade , Tremor/diagnóstico , Tremor/genéticaRESUMO
PURPOSE OF REVIEW: Non-amnestic (or atypical) presentations of neurodegenerative dementias are underrecognized and underdiagnosed, including posterior cortical atrophy (PCA) syndrome, which is characterized by prominent visuospatial and visuoperceptual dysfunction at presentation. It is most commonly due to Alzheimer's disease pathology, while Lewy body disease, corticobasal degeneration, and prion disease are neuropathological entities that are less frequently associated with PCA. The diagnosis of PCA is often delayed, to the detriment of the patient, and awareness and understanding of PCA will improve detection, prognostication, and treatment. RECENT FINDINGS: The natural history of PCA appears to be distinct from typical Alzheimer's disease and significant heterogeneity exists within the PCA syndrome, with the underlying causes of this heterogeneity beginning to be explored. Functional and molecular imaging can assist in better understanding PCA, particularly assessment of network disruptions that contribute to clinical phenotypes. Cerebrospinal fluid biomarkers are useful to detect underlying pathology, but measures of retinal thickness are less promising. There are currently no adequate treatment options for PCA. SUMMARY: Continued efforts to characterize PCA are needed, and greater awareness and understanding of atypical presentations of neurodegenerative dementias could serve to elucidate pathobiological mechanisms of underlying disease.
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Doença de Alzheimer/patologia , Atrofia/patologia , Córtex Cerebral/patologia , Doença por Corpos de Lewy/patologia , Doença de Alzheimer/fisiopatologia , Atrofia/fisiopatologia , Biomarcadores , Córtex Cerebral/fisiopatologia , Humanos , Doença por Corpos de Lewy/fisiopatologiaRESUMO
The initiation and continuation of immune-based therapies to treat and prevent complications of inflammatory neuro-ophthalmologic disorders during the 2019 novel coronavirus (COVID-19) pandemic is the subject of considerable debate. In each case, a treatment decision must be reached based on best clinical practices for the disorder, patient comorbidities, the current state of knowledge about the pathogenesis and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the utilization of hospital and community resources. Unfortunately, the evidence needed to standardize the decision-making process for each neuro-ophthalmologic disorder is currently absent and is likely to require months or years to develop based on the accrual of robust international data sets. In this article, we review the current understanding of SARS-CoV-2 and COVID-19 complications to provide a framework for approaching the treatment of inflammatory neuro-ophthalmic disorders during the COVID-19 viral pandemic.
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Oftalmopatias/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Pandemias , Pneumonia Viral/epidemiologia , COVID-19 , Infecções por Coronavirus/imunologia , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Imunomodulação , Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Neurite Óptica/tratamento farmacológico , Pneumonia Viral/imunologia , SARS-CoV-2RESUMO
Visual complaints are common in Parkinson's disease (PD), but transient visual loss has not previously been defined as a feature of parkinsonian-related disease. We report a patient with recurrent daily episodes of transient and disabling visual loss due to PD-related non-motor fluctuation. During his visit, he experienced one such episode, which allowed for close observation and examination during and after the visual loss. Implications for localization of the visual loss are reviewed in the context of visual pathway disturbances in PD.
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Here we present a patient with persistent central visual oscillopsia, review the literature on this condition, and report results from an experimental intervention using repetitive transcranial magnetic stimulation. A 57-year-old man reported persistent visual oscillopsia after a traumatic brain injury suffered 20 years earlier. Symptoms were presumed to be of cortical origin given his normal eye movements, eye stability, and peripheral vestibular function. Furthermore, he reported oscillopsia with visual imagery during eye closure. Occipital lesions damaging white matter connections identified on magnetic resonance imaging were suspected to be the cause of his symptoms. Repetitive transcranial magnetic stimulation was applied to the left extrastriate visual motion area V5/MT, to bilateral V5/MT, and to bilateral striate visual area V1. The primary outcome measure was dynamic visual acuity. Secondary outcome measures were gaze stabilization testing and subjective improvement as noted by interviews of the patient. Gaze stabilization and dynamic visual acuity testing revealed no difference between pre- and post-intervention with repetitive transcranial magnetic stimulation. The patient reported symptomatic improvement in large-amplitude oscillations that persisted for at least 12 months, but stated that smaller-amplitude oscillations were unchanged. Pathologies associated with central oscillopsia in the literature include neuromyelitis optica spectrum disorder, stroke, migraine without infarction, and psychological trauma. The patient's reported improvement in large- but not small-amplitude oscillopsia suggests that these symptoms may result from different neurophysiological mechanisms. Repetitive transcranial magnetic stimulation did not result in clinically significant improvement, suggesting a need for other strategies to treat this condition.
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Imageamento por Ressonância Magnética/métodos , Estimulação Magnética Transcraniana/métodos , Transtornos da Visão/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Visão/patologiaRESUMO
BACKGROUND/AIMS: Laser interstitial thermal therapy (LITT) has become an alternative to open-resective surgery for refractory mesial temporal lobe epilepsy (MTLE). Occurrence of visual field defects (VFDs) following open surgery for MTLE is reported at 52-100%. We examined the rate of VFDs following LITT for amygdalohippocampectomy (AHE) and correlated the occurrence of VFDs with damage to the optic radiations, assessed by diffusion tensor tractography (DTI). METHODS: We performed a retrospective analysis of 5 patients who underwent LITT-AHE for medically refractory MTLE. We examined the association between VFDs and optic radiation damage by correlating postprocedural visual field testing with qualitative assessment of optic radiation fiber tracts. RESULTS: Postoperative assessments showed that 4 patients had normal visual field testing, and 1 had a right superior quadrantanopsia (20%). We performed 3-dimensional reconstruction of the optic radiation, laser probe trajectory, and ablation volume. Damage to Meyer's loop was determined consistent with the VFD. CONCLUSIONS: Short-term follow-up in our series suggests that laser ablation AHE may be associated with a lower rate of VFD than has been reported for open AHE. Our results suggest that incorporating optic radiation mapping through DTI may preoperatively help to minimize the risk of VFD following laser ablation AHE.
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Tonsila do Cerebelo/cirurgia , Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Terapia a Laser/tendências , Transtornos da Visão/etiologia , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Seguimentos , Hipocampo/diagnóstico por imagem , Humanos , Terapia a Laser/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transtornos da Visão/diagnóstico por imagem , Campos Visuais/fisiologia , Vias Visuais/diagnóstico por imagemRESUMO
INTRODUCTION: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. METHODS: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. RESULTS: A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. DISCUSSION: There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.
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Encefalopatias/classificação , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Encefalopatias/fisiopatologia , Encefalopatias/psicologia , HumanosRESUMO
Endogenous testosterone in the aging man has been scrutinized extensively in regard to its effects on performance in many cognitive domains, especially verbal fluency, visuospatial and visuoperceptual abilities, memory, and executive function. Studies of testosterone supplementation have sought to identify potential cognitive improvements in men with and without baseline cognitive impairment, and have had a wide range of results. The variability in outcomes is likely related, in part, to the lack of consensus on methods for testosterone measurement and supplementation and, in part, to the disparate measures of cognitive function used in randomized controlled studies. Despite the limitations imposed by such inconsistent methods, promising associations have been found between cognition and testosterone supplementation in both eugonadal men and men with low testosterone levels, with and without baseline cognitive dysfunction. This systematic review highlights the cognitive measures used in and the outcomes of existing studies of testosterone and cognition in aging men. The review suggests that larger studies and a more standardized approach to assessment will be needed before we can fully understand and realize sustained benefits from testosterone supplementation in the elderly male population, particularly given the substantial increase in testosterone supplementation in clinical practice.
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Envelhecimento/efeitos dos fármacos , Androgênios/farmacologia , Cognição/efeitos dos fármacos , Testosterona/farmacologia , Idoso , Humanos , MasculinoRESUMO
BACKGROUND: Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. METHODS: We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I2. FINDINGS: We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 59·4 years (95% CI 58·9-59·8; I2=77%), 60% (56-64; I2=35%) were women, and 80% (72-89; I2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid ß in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I2=89%), Lewy body disease (44%, 25-62; I2=77%), and cerebrovascular injury (42%, 24-60; I2=88%). INTERPRETATION: These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity. FUNDING: None.