Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease.

Alzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [18 F]fluorodeoxyglucose (FDG) PET, tau uptake on [18 F]AV-1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. We aimed to examine multimodal neuroimaging relationships in individuals with atypical AD, using univariate and multivariate techniques at region- and voxel-level. Forty atypical AD patients underwent MRI, FDG-PET, tau-PET, beta-amyloid PET, and DTI. Patients were all beta-amyloid positive. Partial Pearson's correlations were performed between tau and FDG standardized uptake value ratios, gray matter MRI-volumes and white matter tract fractional anisotropy. Sparse canonical correlation analysis was applied to identify multivariate relationships between the same quantities. Voxel-level associations across modalities were also assessed. Tau showed strong local negative correlations with FDG metabolism in the occipital and frontal lobes. Tau in frontal and parietal regions was negatively associated with temporoparietal gray matter MRI-volume. Fractional anisotropy in a set of posterior white matter tracts, including the splenium of the corpus callosum, cingulum, and posterior thalamic radiation, was negatively correlated with parietal and occipital tau, atrophy and, predominantly, with hypometabolism. These results support the view that tau is the driving force behind neurodegeneration in atypical AD, and that a breakdown in structural connectivity is related to cortical neurodegeneration, particularly hypometabolism.

[18 F]AV-1451 tau-PET and primary progressive aphasia.

OBJECTIVES: To assess [18 F]AV-1451 tau-PET (positron emission tomography) uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic, and agrammatic), examine regional uptake patterns of [18 F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [18 F]AV-1451, [18 F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging) to differentiate the PPA variants. METHODS: We performed statistical parametric mapping of [18 F]AV-1451 across 40 PPA patients (logopenic-PPA = 14, semantic-PPA = 13, and agrammatic-PPA = 13) compared to 80 cognitively normal, Pittsburgh compound B-negative controls, age and gender matched 2:1. Principal component analysis of regional [18 F]AV-1451 tau-PET standard uptake value ratio was performed to understand underlying patterns of [18 F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility. RESULTS: Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA, and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder patterns of focal [18 F]AV-1451 uptake. Semantic-PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic-PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical gray matter structures, compared to controls and semantic-PPA. The principal component analysis of regional [18 F]AV-1451 indicated two primary dimensions, a severity dimension that distinguished logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal versus temporal contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic utility of [18 F]AV-1451was superior to MRI and at least equal to FDG-PET. INTERPRETATION: [18 F]AV-1451binding characteristics differ across the PPA variants and were excellent at distinguishing between the variants. [18 F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18 F]AV-1451 may have clinical diagnostic utility in PPA. Ann Neurol 2018 Ann Neurol 2018;83:599-611.

[18 F]AV-1451 clustering of entorhinal and cortical uptake in Alzheimer's disease.

OBJECTIVE: To use a cluster analysis of [18 F]AV-1451 tau-PET data to determine how subjects with Alzheimer's disease (AD) vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in AD. METHODS: We calculated [18 F]AV-1451 uptake in entorhinal cortex and neocortex in 62 amyloid-positive AD patients (39 typical and 23 atypical presentation). tau-PET (positron emission tomography) values were normalized to the cerebellum to create standard uptake value ratios (SUVRs). tau-PET SUVRs were log-transformed and clustered blinded to clinical information into three groups using K-median cluster analysis. Demographics, clinical phenotype, cognitive performance, and apolipoprotein e4 frequency were compared across clusters. RESULTS: The cluster analysis identified a cluster with low entorhinal and cortical uptake (ELo /CLo ), one with low entorhinal but high cortical uptake (ELo /CHi ), and one with high cortical and entorhinal uptake (EHi /CHi ). Clinical phenotype differed across clusters, with typical AD most commonly observed in the ELo /CLo and EHi /CHi clusters, and atypical AD most commonly observed in the ELo /CHi cluster. The ELo /CLo cluster had an older age at PET and onset than the other clusters. Apolipoprotein e4 frequency was lower in the ELo /CHi cluster. The EHi /CHi cluster had the worst memory impairment, whereas the ELo /CHi cluster had the worst impairment in nonmemory domains. INTERPRETATION: This study demonstrates considerable variability in [18 F]AV-1451 tau-PET uptake in AD, but shows that a straightforward clustering based on entorhinal and cortical uptake maps well onto age and clinical presentation in AD. Ann Neurol 2018 Ann Neurol 2018;83:248-257.

18 F-AV-1451 uptake differs between dementia with lewy bodies and posterior cortical atrophy.

BACKGROUND: Posterior cortical atrophy and dementia with Lewy bodies are 2 distinct clinical syndromes, yet they can overlap in symptoms and occipital hypometabolism. Patients with dementia with Lewy bodies often have overlapping Alzheimer's disease pathology. Similarly, Lewy bodies can be found in patients with posterior cortical atrophy. We investigated differences in the distribution and magnitude of F18-AV-1451 uptake in patients with these 2 syndromes. METHODS: Consecutive patients with probable dementia with Lewy bodies (n = 33), posterior cortical atrophy (n = 18), and cognitively unimpaired controls (n = 100) underwent 18 F-AV-1451 positron emission tomography. Regional differences in AV-1451 uptake were assessed using voxel-wise and an atlas-based approach. The greatest differences in AV-1451 uptake between patient groups were identified using area under receiver operating curve statistics, and a composite region was derived. RESULTS: AV-1451 uptake in both patient groups was predominantly localized to the lateral occipital regions, but the magnitude of uptake was markedly greater in posterior cortical atrophy compared with dementia with Lewy bodies. The posterior cortical atrophy group showed the greatest AV-1451 uptake throughout all the gray matter compared with that in other groups. The occipital composite region, consisting of superior, middle, and inferior occipital cortices, distinguished posterior cortical atrophy from dementia with Lewy bodies (area under the curve >0.97; P < 0.001, Bonferroni-corrected) with excellent sensitivity (88%) and specificity (100%). CONCLUSIONS: Posterior cortical atrophy and dementia with Lewy bodies can share clinical features, and although the pattern of AV-1451 uptake in occipital cortices overlaps between these 2 syndromes, its magnitude is significantly higher in posterior cortical atrophy. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The role of age on tau PET uptake and gray matter atrophy in atypical Alzheimer's disease.

INTRODUCTION: Little is known about the role of age on neurodegeneration and protein deposition in atypical variants of Alzheimer's disease (AD). METHODS: Regional tau and ß-amyloid positron emission tomography standard uptake value ratios and gray matter volumes were calculated in a cohort of 42 participants with atypical AD. The relationship between regional metrics and age was modeled using a Bayesian hierarchical linear model. RESULTS: Age was strongly associated with tau uptake across all cortical regions, particularly parietal, with greater uptake in younger participants. Younger age was associated with smaller parietal and lateral temporal volumes. Regional ß-amyloid differed little by age. Age showed a stronger association with tau than volume and ß-amyloid in all cortical regions. Age was not associated with cognitive performance. DISCUSSION: Age is an important determinant of severity of cortical tau uptake in atypical AD, with young participants more likely to show widespread and severe cortical tau uptake.

Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

Imaging correlations of tau, amyloid, metabolism, and atrophy in typical and atypical Alzheimer's disease.

INTRODUCTION: Neuroimaging modalities can measure different aspects of the disease process in Alzheimer's disease, although the relationship between these modalities is unclear. METHODS: We assessed subject-level regional correlations between tau on [18F]AV-1451 positron emission tomography (PET), ß amyloid on Pittsburgh compound B PET, hypometabolism on [18F] fluorodeoxyglucose PET, and cortical thickness on magnetic resonance imaging in 96 participants with typical and atypical Alzheimer's disease presentations. We also assessed how correlations between modalities varied according to age, presenting syndrome, tau-PET severity, and asymmetry. RESULTS: [18F]AV-1451 uptake showed the strongest regional correlation with hypometabolism. Correlations between [18F]AV-1451 uptake and both hypometabolism and cortical thickness were stronger in participants with greater cortical tau severity. In addition, age, tau asymmetry, and clinical diagnosis influenced the strength of the correlation between [18F]AV-1451 uptake and cortical thickness. DISCUSSION: These findings support a close relationship between tau and hypometabolism in Alzheimer's disease but show that correlations between neuroimaging modalities vary across participants.

Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia Associated with Dementia with Lewy Bodies: A Pilot Study.

BACKGROUND/AIMS: Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. METHODS: We performed a 12-week pilot trial of armodafinil therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The patients underwent neurologic examinations, a neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks. Safety assessment included laboratory examinations, QTc interval, and heart rate. Tolerability was assessed by analysis of adverse events. Data were analyzed using the last-observation-carried-forward method. RESULTS: Of 20 participants, 17 completed the protocol. The median age was 72 years, most of the participants were men (80%), and most had spouses as caregivers. The Epworth Sleepiness Scale (p < 0.001), Maintenance of Wakefulness Test (p = 0.003), and Clinical Global Impression of Change (p < 0.001) scores improved at week 12. The Neuropsychiatric Inventory total score (p = 0.003), visual hallucinations (p = 0.003), and agitation (p = 0.02) improved at week 4. Caregiver overall quality of life improved at week 12 (p = 0.004). No adverse events occurred. CONCLUSION: These pilot data suggest improvements in hypersomnia and wakefulness and reasonable safety and tolerability of armodafinil therapy in hypersomnolent patients with DLB. Our findings inform the use of pharmacologic strategies for managing hypersomnolence in these patients.

Fluorodeoxyglucose F18 positron emission tomography in a case of slowly progressive pure alexia.

We describe a 71-year-old patient with slowly progressive pure alexia in which analysis of her fluorodeoxyglucose FDG-PET scan revealed an area of focal hypometabolism in the visual word form area. She presented with difficulty reading. Examination revealed pure alexia with preservation of other cognitive domains. Brain MRI revealed only slight atrophy. A Fluorodeoxyglucose F18 positron emission tomography scan revealed hypometabolism in the occipital cortex bilaterally, left greater than right, with normal metabolism elsewhere in the brain. This case highlights the utility of FDG-PET scan in evaluating focal neurodegenerative conditions before clear atrophy can be seen on MRI.

Resolution of neuropsychological and FDG-PET abnormalities in a patient with neuropsychiatric systemic lupus erythematosus.

Many patients with systemic lupus erythematosus have central nervous system involvement. Routine diagnostic studies may not yield evidence of neuropsychiatric dysfunction and are therefore not useful as objective measures to monitor treatment response. We present a case of a 64-year-old woman whom we diagnosed with systemic lupus erythematosus by the American College of Rheumatology criteria after she reported recent cognitive decline. Neuropsychological assessment showed prominent deficits, and an F-18 fluorodeoxyglucose positron emission tomography scan of the brain showed significant abnormalities. Both the neuropsychiatric and scan abnormalities improved dramatically with immunosuppressive treatment. F-18 fluorodeoxyglucose positron emission tomography shows promise in the diagnosis and treatment monitoring of patients who have lupus with neuropsychiatric involvement.

Steroid-responsive encephalopathy subsequently associated with Alzheimer's disease pathology: a case series.

BACKGROUND: Steroid-responsive encephalopathies can be considered vasculitic or non-vasculitic. Clinicopathological studies of non-vasculitic steroid-responsive encephalopathy are unusual, but can explain the range of diagnoses consistent with a steroid-responsive presentation in life. OBJECTIVE: To extend the range of clinical features and pathological findings consistent with steroid-responsive encephalopathy. Design, methods, and patients: A clinicopathological case series of four patients (two women, ages 54-71 years) with steroid-responsive encephalopathy followed at this institution until the time of death. RESULTS: Clinical features were suggestive of Creutzfeld-Jakob disease (CJD), dementia with Lewy bodies (DLB), and parkinsonism, but pathological examination revealed only Alzheimer's disease-related findings without evidence of Lewy bodies or prion disease in all cases. All patients demonstrated marked, sustained improvement following steroid treatment, based on clinical, magnetic resonance imaging, and/or electroencephalogram studies. Alzheimer's disease was not diagnosed in life due to the atypical clinical features, lack of hippocampal atrophy on brain imaging, and a dramatic symptomatic response to steroids. CONCLUSIONS: Steroid-responsive encephalopathy is the clinical presentation of some patients with Alzheimer's disease-related pathology at autopsy, and can be consistent with the clinical diagnoses of parkinsonism, DLB, or CJD disease in life.

Three cases of Creutzfeldt-Jakob disease presenting with a predominant dysexecutive syndrome.

Creutzfeldt-Jakob disease (CJD) is a rare, uniformly fatal prion disease. Although CJD commonly presents with rapidly progressive dementia, ataxia, and myoclonus, substantial clinicopathological heterogeneity is observed in clinical practice. Unusual and predominantly cognitive clinical manifestations of CJD mimicking common dementia syndromes are known to pose as an obstacle to early diagnosis and prognosis. We report a series of three patients with probable or definite CJD (one male and two females, ages 52, 58 and 68) who presented to our tertiary behavioral neurology clinic at Mayo Clinic Rochester that met criteria for a newly defined progressive dysexecutive syndrome. Glucose hypometabolism patterns assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) strongly resembled those of dysexecutive variant of Alzheimer's disease (dAD). However, magnetic resonance imaging (MRI) demonstrated restricted diffusion in neocortical areas and deep nuclei, while cerebrospinal fluid biomarkers indicated abnormal levels of 14-3-3, total-tau, and prion seeding activity (RT-QuIC), establishing the diagnosis of CJD. Electroencephalogram (EEG) additionally revealed features previously documented in atypical cases of CJD. This series of clinical cases demonstrates that CJD can present with a predominantly dysexecutive syndrome and FDG-PET hypometabolism typically seen in dAD. This prompts for the need to integrate information on clinical course with multimodal imaging and fluid biomarkers to provide a precise etiology for dementia syndromes. This has important clinical implications for the diagnosis and prognosis of CJD in the context of emerging clinical characterization of progressive dysexecutive syndromes in neurodegenerative diseases like dAD.

Psychiatric manifestations of voltage-gated potassium-channel complex autoimmunity.

The authors describe the neuropsychiatric spectrum of voltage-gated potassium-channel complex (VGKC) autoimmunity among 67 seropositive patients; 2 had initially been assigned a primary psychiatric diagnosis. Diverse manifestations were recorded, often affective-predominant. Symptoms for 24 patients with florid presentations included confusion, 92%; memory impairment, 75%; personality change, 58%; depression, 33%; and anxiety, 29%. Of 15 who received immunotherapy, 67% improved. Forty-three patients with milder presentations or low positive VGKC complex Ab values are also described. Neuropsychiatric presentations were significantly associated with higher autoantibody values. Improvements were most evident in patients treated early, which emphasizes the need for early diagnosis and immunotherapy initiation.

Posterior cortical atrophy phenotypic heterogeneity revealed by decoding 18F-FDG-PET.

Posterior cortical atrophy is a neurodegenerative syndrome with a heterogeneous clinical presentation due to variable involvement of the left, right, dorsal and ventral parts of the visual system, as well as inconsistent involvement of other cognitive domains and systems. 18F-fluorodeoxyglucose (FDG)-PET is a sensitive marker for regional brain damage or dysfunction, capable of capturing the pattern of neurodegeneration at the single-participant level. We aimed to leverage these inter-individual differences on FDG-PET imaging to better understand the associations of heterogeneity of posterior cortical atrophy. We identified 91 posterior cortical atrophy participants with FDG-PET data and abstracted demographic, neurologic, neuropsychological and Alzheimer's disease biomarker data. The mean age at reported symptom onset was 59.3 (range: 45-72 years old), with an average disease duration of 4.2 years prior to FDG-PET scan, and a mean education of 15.0 years. Females were more common than males at 1.6:1. After standard preprocessing steps, the FDG-PET scans for the cohort were entered into an unsupervised machine learning algorithm which first creates a high-dimensional space of inter-individual covariance before performing an eigen-decomposition to arrive at a low-dimensional representation. Participant values ('eigenbrains' or latent vectors which represent principle axes of inter-individual variation) were then compared to the clinical and biomarker data. Eight eigenbrains explained over 50% of the inter-individual differences in FDG-PET uptake with left (eigenbrain 1) and right (eigenbrain 2) hemispheric lateralization representing 24% of the variance. Furthermore, eigenbrain-loads mapped onto clinical and neuropsychological data (i.e. aphasia, apraxia and global cognition were associated with the left hemispheric eigenbrain 1 and environmental agnosia and apperceptive prosopagnosia were associated with the right hemispheric eigenbrain 2), suggesting that they captured important axes of normal and abnormal brain function. We used NeuroSynth to characterize the eigenbrains through topic-based decoding, which supported the idea that the eigenbrains map onto a diverse set of cognitive functions. These eigenbrains captured important biological and pathophysiologic data (i.e. limbic predominant eigenbrain 4 patterns being associated with older age of onset compared to frontoparietal eigenbrain 7 patterns being associated with younger age of onset), suggesting that approaches that focus on inter-individual differences may be important to better understand the variability observed within a neurodegenerative syndrome like posterior cortical atrophy.

Progressive dysexecutive syndrome due to Alzheimer's disease: a description of 55 cases and comparison to other phenotypes.

We report a group of patients presenting with a progressive dementia syndrome characterized by predominant dysfunction in core executive functions, relatively young age of onset and positive biomarkers for Alzheimer's pathophysiology. Atypical frontal, dysexecutive/behavioural variants and early-onset variants of Alzheimer's disease have been previously reported, but no diagnostic criteria exist for a progressive dysexecutive syndrome. In this retrospective review, we report on 55 participants diagnosed with a clinically defined progressive dysexecutive syndrome with 18F-fluorodeoxyglucose-positron emission tomography and Alzheimer's disease biomarkers available. Sixty-two per cent of participants were female with a mean of 15.2 years of education. The mean age of reported symptom onset was 53.8 years while the mean age at diagnosis was 57.2 years. Participants and informants commonly referred to initial cognitive symptoms as 'memory problems' but upon further inquiry described problems with core executive functions of working memory, cognitive flexibility and cognitive inhibitory control. Multi-domain cognitive impairment was evident in neuropsychological testing with executive dysfunction most consistently affected. The frontal and parietal regions which overlap with working memory networks consistently demonstrated hypometabolism on positron emission tomography. Genetic testing for autosomal dominant genes was negative in all eight participants tested and at least one APOE ε4 allele was present in 14/26 participants tested. EEG was abnormal in 14/17 cases with 13 described as diffuse slowing. Furthermore, CSF or neuroimaging biomarkers were consistent with Alzheimer's disease pathophysiology, although CSF p-tau was normal in 24% of cases. Fifteen of the executive predominate participants enrolled in research neuroimaging protocols and were compared to amnestic (n = 110), visual (n = 18) and language (n = 7) predominate clinical phenotypes of Alzheimer's disease. This revealed a consistent pattern of hypometabolism in parieto-frontal brain regions supporting executive functions with relative sparing of the medial temporal lobe (versus amnestic phenotype), occipital (versus visual phenotype) and left temporal (versus language phenotype). We propose that this progressive dysexecutive syndrome should be recognized as a distinct clinical phenotype disambiguated from behavioural presentations and not linked specifically to the frontal lobe or a particular anatomic substrate without further study. This clinical presentation can be due to Alzheimer's disease but is likely not specific for any single aetiology. Diagnostic criteria are proposed to facilitate additional research into this understudied clinical presentation.

Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease.

The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [18F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.

The purpose and neurobiology of theory of mind functions.

Theory of Mind (ToM) refers to a cognitive process which allows an individual to "place him/herself" in the other person's "mind," so as to comprehend the latter's cognitive and emotional status, so as to predict his/her behavior and emotional response to a particular situation. ToM is necessary for everyday interaction among individuals and accounts for such human traits as empathy, compassion, and deceit. It is also particularly important in the relationship between a healer and his or her client, as well as in the God-human relationship. Recent research in the area of neurosciences has identified a specific brain "system" responsible for ToM, as well as described how these functions may be affected in certain neuropsychiatric conditions. In this article, we discuss the definition and neurobiological substrate of ToM. In addition, we discuss the cognitive steps important to achieve an "accurate" theory of mind, its relevance to "self-knowledge," and its limitations. We also review some of the data concerning abnormalities and "distortion" of ToM in neuropsychiatric disorders and aberrant human behavior.

Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year.

In this prospective evaluation of serum and CSF samples, all but two CSF GFAPα-IgG positive patients had autoimmune meningoencephalomyelitis while serum GFAPα-IgG positivity alone was less specific. Phenotypes were diverse among patients that were serum positive only. Adult and pediatric clinical presentations were similar. Most patients were immunotherapy responsive. Co-existing NMDA-R-IgG and cancer were associated with lack of response to first-line immunotherapy. Among patients with follow-up information, 18% had relapses. This study demonstrates CSF GFAPα-IgG is a specific autoimmune meningoencephalomyelitis biomarker, with favorable corticosteroid response. Lack of response should prompt evaluation for co-existing NMDA-R-IgG or malignancy.

Regional Distribution, Asymmetry, and Clinical Correlates of Tau Uptake on [18F]AV-1451 PET in Atypical Alzheimer's Disease.

BACKGROUND: Despite common pathology, Alzheimer's disease (AD) can have multiple clinical presentations which pathological studies suggest result from differences in the regional distribution of tau pathology. Positron emission tomography (PET) ligands are now available that can detect tau proteins in vivo and hence can be used to investigate the biological mechanisms underlying atypical AD. OBJECTIVE: To assess regional patterns of tau uptake on PET imaging in two atypical AD variants, posterior cortical atrophy (PCA) and logopenic progressive aphasia (lvPPA). METHODS: Eighteen PCA and 19 lvPPA subjects that showed amyloid-ß deposition on PET underwent tau-PET imaging with [18F]AV-1451. Group comparisons of tau uptake in PCA and lvPPA were performed using voxel-level and regional-level analyses. We also assessed the degree of lobar tau asymmetry and correlated regional tau uptake to age and performance on clinical evaluations. RESULTS: Both syndromes showed diffuse tau uptake throughout all cortical regions, although PCA showed greater uptake in occipital regions compared to lvPPA, and lvPPA showed greater uptake in left frontal and temporal regions compared to PCA. While lvPPA showed predominant left-asymmetric tau deposition, PCA was more bilateral. Younger subjects showed greater tau uptake bilaterally in frontal and parietal lobes than older subjects, and sentence repetition, Boston naming test, simultanagnosia, and visuoperceptual function showed specific regional tau correlates. CONCLUSION: Tau deposition is closely related to clinical presentation in atypical AD with age playing a role in determining the degree of cortical tau deposition.

Clinicopathological and 123I-FP-CIT SPECT correlations in patients with dementia.

The relationship between clinicopathologic diagnosis and 123I-FP-CIT SPECT in 18 patients with dementia (12 with Lewy body disease) from one center in the United States was assessed. The sensitivity and specificity of abnormal 123I-FP-CIT SPECT with reduced striatal uptake on visual inspection for predicting Lewy body disease were 91.7% and 83.3%, respectively. The mean calculated putamen to occipital ratio (mPOR) based on regions of interest was significantly reduced in Lewy body disease compared to non-Lewy body disease cases (P = 0.002). In this study, abnormal 123I-FP-CIT SPECT was strongly associated with underlying Lewy body disease pathology, supporting the utility of 123I-FP-CIT SPECT in the clinical diagnosis of dementia with Lewy bodies.