Causes Of Rapidly Progressive Dementia Research Articles

Diagnostic Utility of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia.

This study was undertaken to apply established and emerging cerebrospinal fluid (CSF) biomarkers to improve diagnostic accuracy in patients with rapidly progressive dementia (RPD). Overlap in clinical presentation and results of diagnostic tests confounds etiologic diagnosis in patients with RPD. Objective measures are needed to improve diagnostic accuracy and to recognize patients with potentially treatment-responsive causes of RPD. Biomarkers of Alzheimer disease neuropathology (amyloid-β 42/40 ratio, phosphorylated tau [p-tau181, p-tau231]), neuroaxonal/neuronal injury (neurofilament light chain [NfL], visinin-like protein-1 [VILIP-1], total tau), neuroinflammation (chitinase-3-like protein [YKL-40], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], glial fibrillary acidic protein [GFAP], monocyte chemoattractant protein-1 [MCP-1]), and synaptic dysfunction (synaptosomal-associated protein 25kDa, neurogranin) were measured in CSF obtained at presentation from 78 prospectively accrued patients with RPD due to neurodegenerative, vascular, and autoimmune/inflammatory diseases; 35 age- and sex-matched patients with typically progressive neurodegenerative disease; and 72 cognitively normal controls. Biomarker levels were compared across etiologic diagnoses, by potential treatment responsiveness, and between patients with typical and rapidly progressive presentations of neurodegenerative disease. Alzheimer disease biomarkers were associated with neurodegenerative causes of RPD. High NfL, sTREM2, and YKL-40 and low VILIP-1 identified patients with autoimmune/inflammatory diseases. MCP-1 levels were highest in patients with vascular causes of RPD. A multivariate model including GFAP, MCP-1, p-tau181, and sTREM2 identified the 44 patients with treatment-responsive causes of RPD with 89% accuracy. Minimal differences were observed between typical and rapidly progressive presentations of neurodegenerative disease. Selected CSF biomarkers at presentation were associated with etiologic diagnoses and treatment responsiveness in patients with heterogeneous causes of RPD. The ability of cross-sectional biomarkers to inform upon mechanisms that drive rapidly progressive neurodegenerative disease is less clear. ANN NEUROL 2024;95:299-313.

Improving Early Recognition of Potentially Treatable Causes of Rapidly Progressive Dementia (P5-12.001)

Improving Early Recognition of Potentially Treatable Causes of Rapidly Progressive Dementia (P5-12.001)

Causes of Rapidly Progressive Dementia in a Prospectively Accrued Cohort (P2-6.009)

Causes of Rapidly Progressive Dementia in a Prospectively Accrued Cohort (P2-6.009)

Frequency, Classification, and Timing of Movement Disorders in Rapidly Progressive Dementia (P14-11.004)

<h3>Objective:</h3> To compare and classify movement disorders in patients with specific causes of rapidly progressive dementia (RPD). <h3>Background:</h3> Many diseases present with RPD. The broad differential presents a unique challenge for the clinician who must rapidly organize and interpret tests to provide a timely clinical diagnosis for the patient with RPD. Movement disorders are associated with several different causes of RPD; their emergence, classification, and progression may provide clues to the specific diagnosis in patients with RPD. <h3>Design/Methods:</h3> Patients with RPD were prospectively enrolled between February 2016 and August 2022 at two tertiary care centers. Two neurologists independently determined etiologic diagnoses. A third neurologist systematically reviewed research records to identify movement disorders (e.g., parkinsonism, tremor, ataxia, myoclonus, dystonia, etc.) and classified these when present. Associations between movement disorders and specific causes of RPD were considered using Fisher’s exact test. <h3>Results:</h3> 154 patients met criteria for RPD (46.7% female). The median age-at-symptom onset was 66.0 years old (range: 18.3–84.7 years). Movement disorders were detected at presentation in 45/154 (29.2%) patients and in 73/154 (47.4%) patients at some point in the illness course. Gait disorders (n=40, 52.6%) were the most frequent movement disorder observed, followed by tremor (n=30, 40.5%), rigidity (n=24, 32.4%), ataxia (n=19, 25.7%) and myoclonus (n=19, 25.7%). Movement disorders were more commonly associated with prion disease (OR=3.65, 95% CI 1.27–11.93, p=0.008), and appeared on average 89 days after symptomatic onset. Detection of myoclonus (OR=6.80, 95%CI 2.0–22.54, p&lt;0.005) was associated with higher odds of CJD, with average time from symptom onset to myoclonus of 118 days. Bradykinesia was associated with Alzheimer disease related dementias (OR=7.38, 95%CI 1.54–46.14, p=0.004). <h3>Conclusions:</h3> Detection and classification of movement disorders may inform etiologic diagnosis in patients with RPD. <b>Disclosure:</b> Dr. Turcano has nothing to disclose. Mr. Satyadev has nothing to disclose. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Alzheimer’s Tennessee. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Charlotte County Medical Society, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.

Determining Etiologic Diagnoses in Patients with Rapidly Progressive Dementia

AbstractBackgroundOverlap in the presenting clinical features and test results in patients with rapidly progressive dementia (RPD) confounds the etiologic diagnoses of RPD, contributing to diagnostic delays, missed treatment opportunities, and poorer outcomes. There is a need to improve diagnostic accuracy in patients with RPD, with particular emphasis on identifying patients with potentially treatment‐responsive causes of RPD early in the symptomatic course.MethodPatients with RPD were prospectively enrolled and evaluated in inpatient settings and outpatient subspecialty (memory) clinics at Washington University (Saint Louis, MO; 2016–2019) and Mayo Clinic (Jacksonville, FL; 2020–2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of widely accessible diagnostic testing and referencing established diagnostic criteria. Diagnostic disagreements were resolved via blinded review by a third specialist. Clinicopathologic correlation was evaluated using neuropathological and genetic data when available.Result160 patients with RPD were assessed, with average age‐at‐symptom onset 60.0±15.9 years; 50% were female. Diagnostic inter‐rater reliability (91% agreement; Cohen’s κ = 0.88, p&lt;0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic or genetic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%—i.e., frontotemporal dementia, Lewy body dementia, vascular cognitive impairment), Creutzfeldt‐Jakob disease (15%), and other causes (15%—e.g., neurosarcoid, metabolic disruptions, neoplastic disease). The average age of patients with potentially treatable causes (AE and selected “other” causes; 54.4±18.2) was younger than those with neurodegenerative dementing illnesses (67.3±9.5) or CJD (67.4±7.9; p&lt;0.001). Patients with potentially treatable causes were more likely to present with altered level of consciousness and seizures (p&lt;0.05). CSF pleocytosis (&gt;5 WBC/hpf) was more common in AE patients (p&lt;0.05).ConclusionEtiologic diagnoses can be reliably established in RPD patients using available clinical data. Treatment‐responsive causes of RPD are common warranting consideration, particularly in younger patients with altered consciousness, seizures, and CSF pleocytosis.

Dissecting the Neuropathological Contributors to Rapidly Progressive Dementia

AbstractBackgroundMost series exploring the causes of rapidly progressive dementia (RPD) rely on clinical diagnoses, with limited pathological confirmation. This approach may underestimate the contributions of Alzheimer disease and related dementias to RPD, recognizing challenges associated with extrapolating clinical phenotypes to neuropathological diagnoses. A clearer understanding of the neuropathological causes of RPD is needed to inform the diagnosis and treatment of patients. To meet this need, we determined the neuropathological causes of RPD within the Mayo Clinic neurodegenerative brain bank.MethodPatients with disease duration &lt;4.0 years (symptom‐onset to death due to dementia) were identified within the Mayo Clinic neurodegenerative brain bank (1998‐2020). Available clinical records were reviewed, and details extracted including demographics, family history, dominant symptoms/signs at onset, and common comorbidities (depression, psychoses, sleep disturbance). Neuropathological diagnoses were assigned following standard protocols.Result310/8586 (3.6%) cases met RPD criteria. Relative to typically progressive cases, prion disease most commonly presented as RPD (74%, 32/43), followed by progressive supranuclear palsy/corticobasal degeneration (PSP/CBD: 7.5%, 142/1894), other frontotemporal lobar degeneration (FTLD: 5.7%, 32/561), Lewy body disease (LBD: 4.1%, 49/1202), and Alzheimer disease (AD: 1.8%, 48/2687). Average age‐at‐symptom onset was 69.5±10.4 years. Patients with rapidly progressive AD were older than others (p&lt;0.01), except LBD. Patients with FTLD were younger than others (p&lt;0.05), except prion disease. Average disease duration was 2.9±1.0 years: prion diseases had the most rapid disease course (1.6±1.3 years). Comorbid cerebrovascular disease (25.5%), and clinically symptomatic depression (41.3%), psychoses (37.1%) and sleep disturbances (39.4%) were common across groups. Only psychosis was associated with shorter disease duration (β=‐0.31 years, CI95% [‐0.53, ‐0.082]; controlling for age‐at‐symptom onset).ConclusionRapidly progressive neurodegenerative diseases accounted for 3.6% of cases in this neurodegenerative brain bank. Although prion disease commonly presented as RPD, atypical presentations of more prevalent neurodegenerative diseases accounted for most cases. Atypical (rapidly progressive) variants of typical neurodegenerative diseases warrant consideration in clinical practice.

P.006 Etiologic diagnoses of rapidly progressive dementia in a prospective multicenter cohort

Background: Accurate etiologic diagnoses are needed in patients with rapidly progressive dementia (RPD) to ensure access to symptomatic and disease-modifying therapies when available. Methods: Patients with RPD were prospectively enrolled and evaluated at Washington University (Saint Louis, MO; 2016-2019) and Mayo Clinic (Jacksonville, FL; 2020-2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of diagnostic tests; disagreements were resolved via blinded review by a third specialist. Results: 160 RPD patients were enrolled and followed. Average age-at-symptom onset was 60.0±15.9 years; 50% were female. Inter-rater reliability (91% agreement; Cohen’s κ=0.88, p&lt;0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%), Creutzfeldt-Jakob disease (15%), and other causes (15%). Patients with potentially treatable causes of RPD were younger (54.5±18.2 than those with neurodegenerative causes (67.3±9.5; p&lt;0.001), and more likely to present with altered levels of consciousness, seizures, or CSF pleocytosis (p&lt;0.05). Conclusions: Etiologic diagnoses can be reliably established in RPD patients using available clinical data. The prevalence of autoimmune encephalitis in this series justifies routine screening for potentially treatment-responsive causes of RPD, particularly in younger patients.

P.004 Dissecting the neuropathological causes of rapidly progressive dementia

Background: A clear understanding of the neuropathological causes of RPD is needed to inform the diagnosis and treatment of patients with rapidly progressive dementia (RPD). Methods: Patients with &lt;4.0 years from symptom onset to death were identified within the Mayo Clinic Neurodegenerative Brain Bank (1998-2020). Relevant clinical details were extracted from available records. Neuropathological diagnoses were assigned following standard protocols. Results: 310/8586 (3.6%) cases met RPD criteria. Relative to typically progressive cases, prion disease most commonly presented as RPD (74%, 32/43), followed by progressive supranuclear palsy/corticobasal degeneration (PSP/CBD: 7.5%, 142/1894), other frontotemporal lobar degeneration (FTLD: 5.7%, 32/561), Lewy body disease (LBD: 4.1%, 49/1202), and Alzheimer disease (AD: 1.8%, 48/2687). Average age-at-symptom onset was 69.5±10.4 years. Average disease duration was 2.9±1.0 years. Prion diseases had the most rapid disease course (1.6±1.3 years). Comorbid cerebrovascular disease (25.5%), and clinically symptomatic depression (41.3%), psychoses (37.1%), and sleep disturbances (39.4%) were common across groups. Only psychosis was associated with shorter disease duration (β=-0.31 years, CI95% -0.53, -0.082, controlling for age-at-symptomatic onset). Conclusions: Although prion disease commonly presented as RPD, atypical presentations of more prevalent neurodegenerative diseases accounted for most cases of RPD. Rapidly progressive variants of typical neurodegenerative diseases warrant consideration in clinical practice.

Evolving Causes of Rapidly Progressive Dementia: A 5-Year Comparative Study.

Rapidly progressive dementia (RPD) is a clinical syndrome developing in <1 to 2 years. Recent progress in RPD evaluation is significant, so RPD's prevalence may change over time. The aim of our new case series was to estimate the relative frequency of RPDs' causative entities, considering the recent advances in RPDs' diagnosis, and compare the results with those of our previous report. We retrospectively reviewed the medical records of 47 patients who were referred to Attikon University Hospital during a 5-year period for a suspected RPD. Neurodegenerative diseases were the most frequent causes (38%), followed by prion disease (19%) and autoimmune encephalopathy (AE, 17%). AE cases were by far more common than in our previous report, while other than AE secondary causes were significantly decreased. Mean time to dementia was 9 months in neurodegenerative diseases and 5 months in non-neurodegenerative. Main clinical findings across all patients were memory impairment (66%) and behavioral-emotional disturbances (48%). Neurodegenerative diseases are common causes of RPD and have a slower evolution than non-neurodegenerative. Diagnostic novelties enabled the recognition of AE, whereas more common secondary causes are probably now diagnosed in primary settings since the recognition of RPD as distinct clinical entity is continually increasing.

Reader response: In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease.

We read with interest the article by Day et al.,1 which indicated no specific pattern of [18F]-AV-1451 retention was found in patients with rapidly progressive dementia (RPD) resulting from sporadic Creutzfeldt-Jakob disease (sCJD). This finding was in line with a former study that showed that the frequency of tau pathologies could not precisely reflect the deposition of prion protein.2 This work further confirmed that abnormal prion protein deposition in sCJD was not a risk factor for Alzheimer disease (AD), which indicated the [18F]-AV-1451 PET tracer showed a good specificity for paired helical tau filaments observed in AD dementia. In spite of the negative findings of this study, this work may have potential implications concerning the specificity of [18F]-AV-1451 PET retention for paired helical tau filaments. However, a recent study using fluorodeoxyglucose PET (FDG-PET) indicated a close relationship between FDG-PET hypometabolism and neuropathology in cortical, not subcortical, regions in prion disease.3 Further studies are needed to recruit patients with additional causes of RPD to evaluate the clinical applications of in vivo [18F]-AV-1451 PET and FDG-PET imaging in clinical practice.

Rapidly Progressive Dementia in the Outpatient Clinic: More Than Prions.

Published approaches to the evaluation and management of patients with rapidly progressive dementia (RPD) have been largely informed by experience at academic hospitals and national centers specializing in the diagnosis of Creutzfeldt-Jakob disease. Whether these approaches can be applied to patients assessed within lower-acuity outpatient settings is unknown. A total of 96 patients with suspected RPD were assessed within the Washington University School of Medicine (Saint Louis, MO) outpatient memory clinic from February 2006 to February 2016. Consensus etiologic diagnoses were established following independent review of clinical data by 2 dementia specialists. In total, 67/90 (70%) patients manifested with faster-than-expected cognitive decline leading to dementia within 2 years of symptom onset. Female sex (42/67, 63%), median patient age (68.3 y; range, 45.4 to 89.6), and years of education (12 y; range, 6 to 14) were consistent with clinic demographics. Atypical presentations of common neurodegenerative dementing illnesses accounted for 90% (60/67) of RPD cases. Older age predicted a higher odds of amnestic Alzheimer disease dementia (OR, 2.1 per decade; 95% CI, 1.1-3.8; P=0.02). Parkinsonism (OR, 6.9; 95% CI, 1.6-30.5; P=0.01) or cortical visual dysfunction (OR, 10.8; 95% CI, 1.7-69.4; P=0.01) predicted higher odds of another neurodegenerative cause of RPD, including sporadic Creutzfeldt-Jakob disease. The clinical environment influences the prevalence of RPD causes. The clinical evaluation should be adapted to promote detection of common causes of RPD, specific to the practice setting.

An intriguing case of rapidly progressive dementia: Creutzfeldt–Jakob Disease

Although no formal definition exists for what constitutes a rapidly progressive dementia (RPD), generally we use the term when dementia occurs in <1–2 years from illness onset, but more commonly over weeks to months. Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. We report the case of a 65-year-old male with progressive dementia and typical neurologic symptoms, myoclonic jerks, and magnetic resonance imaging findings of Creutzfeldt–Jakob disease (CJD). This case highlights the need for a high index of suspicion to diagnose CJD.

Comprehensive and Methodical: Diagnostic and Management Approaches to Rapidly Progressive Dementia.

Purpose of review The sudden emergence of a change in cognitive abilities or behavior is an important symptom that warrants medical evaluation and may represent the early stages of a rapidly progressive dementia (RPD). To correctly ascertain the cause of RPD in a given patient, the clinician must be methodical and knowledgeable about the range of potential causes and must move forward with supportive treatment, and in some cases empiric treatment, based on clinical features alone. Recent findings Significant advances in prion disease biomarkers, the molecular features of rapidly progressive Alzheimer's disease, and new detection of autoimmune limbic encephalitis disease entities have caused a shift in the diagnostic and treatment framework of RPD. Additionally, in the past decade, emerging retrospective data have led to suggested treatments in autoimmune encephalitis that, if instituted early, can protect patients against residual deficits and disease relapse. Summary Here, we provide an integrative clinical and diagnostic treatment approach that is applicable to the various forms of RPD. We have highlighted the clinical features of selected types of RPD that have experienced advances in the last 10-15years.

Rapidly Progressive Dementia: Prevalence and Causes in a Neurologic Unit of a Tertiary Hospital in Brazil.

Rapidly progressive dementia (RPD) is usually associated with Creutzfeldt-Jakob disease, a fatal condition. Current advances in the understanding of immune-mediated diseases allow the diagnosis of previously unrecognized treatable RPDs. The objective of the study was to describe the prevalence and causes of RPD in a neurology service, identifying potentially reversible causes. We carried out a cross-sectional evaluation of all patients admitted to the neurology unit of a tertiary hospital in Brazil between March 2012 and February 2015. We included patients who had progressed to moderate or severe dementia within a few months or up to 2 years at the time of hospitalization, and used multivariable logistic regression analysis to identify factors associated with a favorable outcome. We identified 61 RPD (3.7%) cases among 1648 inpatients. Mean RPD patients' age was 48 years, and median time to progression was 6.4 months. Immune-mediated diseases represented the most commonly observed disease group in this series (45.9% of cases). Creutzfeldt-Jakob disease (11.5%) and nonprion neurodegenerative diseases (8.2%) were less common in this series. Outcome was favorable in 36/61 (59.0%) RPD cases and in 28/31 (89.3%) of immune-mediated cases. Favorable outcome was associated with shorter time from symptom onset to diagnosis and abnormal cerebrospinal fluid findings. Immune-mediated diseases were the most common cause of RPD in this series. Timely evaluation and diagnosis along with institution of appropriate therapy are required in RPD, especially in view of potentially reversible causes.

The importance of recognizing faciobrachial dystonic seizures in rapidly progressive dementias.

BackgroundCreutzfeldt-Jakob Disease (CJD) is the prototypical cause of rapidly progressive dementia (RPD). Nonetheless, efforts to exclude reversible causes of RPD that mimic prion disease are imperative. The recent expanding characterization of neurological syndromes associated with antibodies directed against neuronal cell surface or sympathic antigens, namely autoimmune encephalitis is shifting paradigms in neurology. Such antigens are well known proteins and receptors involved in synaptic transmission. Their dysfunction results in neuropsychiatric symptoms, psychosis, seizures, movement disorders and RPD. Faciobrachial dystonic seizure (FBDS) is a novel characterized type of seizure, specific for anti-LGI1 encephalitis.ObjectiveIn order to improve clinical recognition we report the cases of two Brazilian patients who presented with characteristic FDBS (illustrated by videos) and anti-LGI1 encephalitis.MethodsWe have included all patients with FBDS and confirmed anti-LGI1 encephalitis and video records of FDBS in two tertiary Brazilian centers: Department of Neurology of Hospital das Clínicas, Sao Paulo University, Sao Paulo, Brazil and Hospital Geral de Fortaleza, Fortaleza, Brazil between January 1, 2011 and December 31, 2015.ResultsBoth patients presented with clinical features of limbic encephalitis associated with FBDS, hyponatremia and normal CSF. None of them presented with tumor and both showed a good response after immunotherapy.ConclusionFBDSs may be confounded with myoclonus and occurs simultaneously with rapid cognitive decline. Unawareness of FDBS may induce to misdiagnosing a treatable cause of RPD as CJD.

Rapidly Progressive Dementia.

This article presents a practical and informative approach to the evaluation of a patient with a rapidly progressive dementia (RPD). Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Aside from prion diseases, the most common causes of RPD are atypical presentations of other neurodegenerative disorders, curable disorders including autoimmune encephalopathies, as well as some infections, and neoplasms. Numerous recent case reports suggest dural arterial venous fistulas sometimes cause RPDs. RPDs, in which patients typically develop dementia over weeks to months, require an alternative differential than the slowly progressive dementias that occur over a few years. Because of their rapid decline, patients with RPDs necessitate urgent evaluation and often require an extensive workup, typically with multiple tests being sent or performed concurrently. Jakob-Creutzfeldt disease, perhaps the prototypical RPD, is often the first diagnosis many neurologists consider when treating a patient with rapid cognitive decline. Many conditions other than prion disease, however, including numerous reversible or curable conditions, can present as an RPD. This chapter discusses some of the major etiologies for RPDs and offers an algorithm for diagnosis.

Rapidly progressive dementia in the “Attikon” University General Hospital of Athens. A one-year experience

Introduction: Rapidly progressive dementia (RPD) is a rare neurological condition which progresses subacutely from days to months. A variety of possible causes of RPD have been reported, such as neurodegenerative, autoimmune, vascular, metabolic/toxic disorders, infections, malignancies, normal pressure hydrocephalus and psychiatric disorders.

Rapidly Progressive Dementia

Diagnosis of rapidly progressive dementia (RPD) poses a complex medical challenge that requires an exhaustive evaluation. Although prion diseases, in particular Creutzfeldt-Jakob disease (CJD), are often suspected, many other nonprion diseases may present as RPD. Our aim was to review the causes of RPD in our center to better understand the underlying conditions. We reviewed clinical, neuroimaging, and cerebrospinal fluid data from patients with RPD admitted to our hospital from 1994 to 2009. Forty-nine patients (mean age at onset 72.4 y) with RPD were admitted to our center during the study period. The mean interval between the onset of symptoms and admission was 4.6 months. The final clinical diagnoses were as follows: nonprion neurodegenerative diseases (36.8%), CJD (30.6%), vascular dementia (8.2%), toxic-metabolic conditions (8.2%), and other disorders (16.2%). Among cases with informed death (n = 19), the average survival time was 8.6 ± 9.5 months. Survival was shorter among patients with prion disease (n = 10) than in those with other diagnoses (n = 9, P = 0.004). In conclusion, nonprion neurodegenerative diseases are the most common cause of RPD in our center. Our results suggest that although CJD is often suspected as a cause of RPD, its frequency depends on the referral differences across specialized centers.

Cerebral Amyloid Angiopathy-Related Inflammation: A Treatable Cause of Rapidly-Progressive Dementia

To the Editor: The first priority of diagnostic evaluation of dementia syndrome is the identification of potentially treatable causes. Cerebral amyloid angiopathy-related inflammation is a recently described diagnostic entity that is characterized by a treatment-responsive, rapidly-progressive dementia syndrome. It has been suggested that it can be noninvasively diagnosed on the basis of a characteristic combination of clinical and radiological features. We present a representative case and discuss typical findings.

Rapidly Progressive Dementia - Clinical Aspects and Management

Although no precise definition for rapidly progressive dementia (RPD) exists, this term is generally used to refer to cases with significant and progressive cognitive impairment that occurs over weeks or months. RPD represents an unusual but severe condition that causes distress not only for patients and their relatives but also for the clinicians involved, as multiple investigations and decisions about management must be made urgently to avoid misdiagnosing a treatable condition and to preserve as much of the neural tissue as possible from definite damage. While Creutzfeldt-Jacob disease (CJD) has for a long period of time been regarded as the prototype of RPD, this infrequent but severe condition can be produced by an extensive variety of causes such as various endocrine, metabolic or toxic disorders, central nervous system (CNS) infections, primary or secondary CNS neoplasms, various CNS vasculitides and various autoimmune conditions in which autoantibodies against neural tissue are produced, whether in the presence of a neoplasm or not. However, even in the more common and usually slowly progressive dementias such as Alzheimer’s disease, frontotemporal lobar degeneration, dementia with Lewy bodies and other degenerative dementias, as well as vascular dementia, establishment and progression of the disease is occasionally surprisingly accelerated, leading to a clinical presentation of RPD. The few published case series of RPD have shown that the relative frequency of underlying diseases depends mainly on the clinical setting. Thus, CJD has been found to be the most prevalent cause in referral centres for spongiform encephalopathies, while secondary causes are more prevalent in general referral centres for dementia diagnosis. In clinical practice, for the cases presenting with RPD, the diagnostic procedure must be exhaustive, starting with a detailed clinical evaluation and proceeding to a complete laboratory work-up and sophisticated neuroimaging studies. There has been recent enormous progress in imaging, with sensitive new sequences of magnetic resonance imaging and immunology; as a result, a plethora of antibodies against the CNS can now be detected in cases of autoimmune dementias, which has dramatically changed the diagnostic approach and early management of cases of RPD. The same favourable effect in clinical practice comes from the accumulated knowledge of the complex clinical picture of various causes of RPD, associated specific neurological features (pyramidal signs, ataxia, myoclonus) and systematic features (weight loss, hyponatraemia, hepatic disorders) and their mode of progression.