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Objective: We compared the accuracy of amyloid and [ 18 F]Flortaucipir (FTP) tau positron emission tomography (PET) visual reads for distinguishing patients with mild cognitive impairment (MCI) or dementia with fluid biomarker support of Alzheimer's disease (AD)., Methods: Participants with FTP-PET, amyloid-PET, and diagnosis of dementia-AD (n = 102), MCI-AD (n = 41), non-AD diseases (n = 76), and controls (n = 20) were included. AD status was determined independent of PET by cerebrospinal fluid or plasma biomarkers. The mean age was 66.9 years, and 44.8% were women. Three readers interpreted scans blindly and independently. Amyloid-PET was classified as positive/negative using tracer-specific criteria. FTP-PET was classified as positive with medial temporal lobe (MTL) binding as the minimum uptake indicating AD tau (tau-MTL+), positive with posterolateral temporal or extratemporal cortical binding in an AD-like pattern (tau-CTX+), or negative. The majority of scan interpretations were used to calculate diagnostic accuracy of visual reads in detecting MCI/dementia with fluid biomarker support for AD (MCI/dementia-AD)., Results: Sensitivity of amyloid-PET for MCI/dementia-AD was 95.8% (95% confidence interval 91.1-98.4%), which was comparable to tau-CTX+ 92.3% (86.7-96.1%, p = 0.67) and tau-MTL+ 97.2% (93.0-99.2%, p = 0.27). Specificity of amyloid-PET for biomarker-negative healthy and disease controls was 84.4% (75.5-91.0%), which was like tau-CTX+ 88.5% (80.4-94.1%, p = 0.34), and trended toward being higher than tau-MTL+ 75.0% (65.1-83.3%, p = 0.08). Tau-CTX+ had higher specificity than tau-MTL+ (p = 0.0002), but sensitivity was lower (p = 0.02), driven by decreased sensitivity for MCI-AD (80.5% [65.1-91.2] vs. 95.1% [83.5-99.4], p = 0.03)., Interpretation: Amyloid- and tau-PET visual reads have similar sensitivity/specificity for detecting AD in cognitively impaired patients. Visual tau-PET interpretations requiring cortical binding outside MTL increase specificity, but lower sensitivity for MCI-AD. ANN NEUROL 2024;96:476-487., (© 2024 American Neurological Association.)

Approximately 5% of Alzheimer's disease patients develop symptoms before age 65 (early-onset Alzheimer's disease), with either sporadic (sporadic early-onset Alzheimer's disease) or dominantly inherited (dominantly inherited Alzheimer's disease) presentations. Both sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease are characterized by brain amyloid-β accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-β plaque deposition and glucose hypometabolism in sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease individuals. Our analysis included 134 symptomatic sporadic early-onset Alzheimer's disease amyloid-Positron Emission Tomography (PET)-positive cases from the University of California, San Francisco, Alzheimer's Disease Research Center (mean ± SD age 59.7 ± 5.6 years), 89 symptomatic dominantly inherited Alzheimer's disease cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations, 11 C-labelled Pittsburgh Compound B-PET and structural MRI. 18 F-Fluorodeoxyglucose-PET was also available for most participants. Positron Emission Tomography scans from both studies were uniformly processed to obtain a standardized uptake value ratio (PIB 50-70 cerebellar grey reference and FDG 30-60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, apolipoprotein ε4 status and average composite cortical of standardized uptake value ratio. Compared with dominantly inherited Alzheimer's disease, sporadic early-onset Alzheimer's disease participants were older at age of onset (mean ± SD, 54.8 ± 8.2 versus 41.9 ± 8.2, Cohen's d = 1.91), with more years of education (16.4 ± 2.8 versus 13.5 ± 3.2, d = 1) and more likely to be apolipoprotein ε4 carriers (54.6% ε4 versus 28.1%, Cramer's V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 versus 21.2 ± 7.4, d = 0.08). Sporadic early-onset Alzheimer's disease had higher global cortical Pittsburgh Compound B-PET binding (mean ± SD standardized uptake value ratio, 1.92 ± 0.29 versus 1.58 ± 0.44, d = 0.96) and greater global cortical 18 F-fluorodeoxyglucose-PET hypometabolism (mean ± SD standardized uptake value ratio, 1.32 ± 0.1 versus 1.39 ± 0.19, d = 0.48) compared with dominantly inherited Alzheimer's disease. Fully adjusted comparisons demonstrated relatively higher Pittsburgh Compound B-PET standardized uptake value ratio in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in dominantly inherited Alzheimer's disease versus sporadic early-onset Alzheimer's disease. Sporadic early-onset Alzheimer's disease showed relatively greater 18 F-fluorodeoxyglucose-PET hypometabolism in Alzheimer's disease signature temporoparietal regions and caudate nuclei, whereas dominantly inherited Alzheimer's disease showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique Pittsburgh Compound B-PET and 18 F-fluorodeoxyglucose-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolism in sporadic and dominantly inherited early-onset Alzheimer's disease., Competing Interests: Y.L., E.T., B.G., and G.W. report no conflict of interest relevant to this manuscript. J.J.L.-G.’s research is supported by NIH-NIA (K01AG073526), the Alzheimer’s Association (AARFD-21-851415, SG-20-690363), the Michael J. Fox Foundation (MJFF-020770), the Foundation for Barnes-Jewish Hospital and the McDonnell Academy. T.L.S.B., MD, PhD, has investigator-initiated research funding from the NIH, the Alzheimer’s Association, the Barnes-Jewish Hospital Foundation and Avid Radiopharmaceuticals. T.L.S.B. participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly and Company, Biogen, Eisai, Janssen and F. Hoffmann-La Roche, Ltd. She serves as an unpaid consultant to Eisai and Siemens. She is on the Speaker’s Bureau for Biogen. J.C.M., MD, is the Friedman Distinguished Professor of Neurology, Director, Knight ADRC; Associate Director of DIAN and Founding Principal Investigator of DIAN. He is funded by NIH grants # P30 AG066444, P01AG003991, P01AG026276, U19 AG032438 and U19 AG024904. Neither J.C.M. nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Carlos Cruchaga, PhD, receives research support from Biogen, EISAI, Alector and Parabon. The funders of the study had no role in the collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Dr. Cruchaga is a member of the advisory board of Vivid Genetics, Halia Therapeutics and Adx Healthcare. G.S.D.’s research is supported by NIH (K23AG064029, U01AG057195 and U19AG032438), the Alzheimer’s Association and the Chan Zuckerberg Initiative. He serves as a consultant for Parabon NanoLabs, Inc., as a Topic Editor (Dementia) for DynaMed (EBSCO), and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation, Inc. (Canada; uncompensated). He is the co-project PI for a clinical trial in anti-NMDAR encephalitis, which receives support from Horizon Pharmaceuticals. He has developed educational materials for PeerView Media, Inc., and Continuing Education, Inc. He owns stock in ANI Pharmaceuticals. R.J.B., MD, is the director and principal investigator of the DIAN and DIAN-TU-001. He receives research support from the National Institute on Aging of the National Institutes of Health, DIAN-TU Trial Pharmaceutical Partners (Eli Lilly and Company, F. Hoffman-La Roche, Ltd. and Avid Radiopharmaceuticals), Alzheimer’s Association, GHR Foundation, Anonymous Organization, DIAN-TU Pharma Consortium (Active: Biogen, Eisai, Eli Lilly and Company, Janssen, F. Hoffmann-La Roche, Ltd./Genentech, United Neuroscience. Previous: AbbVie, Amgen, AstraZeneca, Forum, Mithridion, Novartis, Pfizer, Sanofi). He has been an invited speaker and consultant for AC Immune, F. Hoffman La Roche, Ltd. and Janssen and a consultant for Amgen and Eisai. J.L., MD, reports speaker fees from Bayer Vital, Biogen and Roche, consulting fees from Axon Neuroscience and Biogen and author fees from Thieme Medical Publishers and W. Kohlhammer GmbH Medical Publishers. In addition, he reports compensation for serving as chief medical officer for MODAG GmbH, is a beneficiary of the phantom share program of MODAG GmbH and is an inventor in a patent ‘Pharmaceutical Composition and Methods of Use’ (EP 22 159 408.8) filed by MODAG GmbH, all activities outside the submitted work. L.I. is currently a full-time employee of Eli Lilly and Company/Avid Radiopharmaceuticals and a minor shareholder of Eli Lilly and Company. His contribution to the work presented in this manuscript was performed while he was affiliated with the University of California San Francisco. G.D.R., MD, receives research support from NIA P30-AG062422, U01 AG057195, R35 AG072362, R56-AG075744, NINDS R21-NS120629, Alzheimer’s Association ZEN-21-848216, American College of Radiology, Rainwater Charitable Foundation, Shenandoah Foundation, Avid Radiopharmaceuticals, Life Molecular Imaging, GE HealthCare and Genentech. He has served as a consultant for Alector, Eli Lilly, Genentech, GE HealthCare, Roche, Johnson & Johnson and Merck. He serves as an associate editor for JAMA Neurology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Tau PET has enabled the visualization of paired helical filaments of 3 or 4 C-terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([ 18 F]fluoro)pyridin-4-yl)-9 H -pyrrolo[2,3-b:4,5c']dipyridine ([ 18 F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images. Methods: We analyzed [ 18 F]PI-2620 PET data from 65 patients with clinical diagnoses associated with AD or FTLD neuropathology; most (60/65) also had amyloid-β (Aβ) PET. Scans were acquired 30-60 min after injection; SUVr maps (reference, inferior cerebellar cortex) were created for the full acquisition and for 10-min truncated sliding windows (30-40, 35-45,…50-60 min). Age- and sex-adjusted z score maps were computed for each patient, relative to 23 Aβ-negative cognitively healthy controls (HC). Mean SUVr in the globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter was extracted for the full and truncated windows. Results: Patients with suspected AD neuropathology (Aβ-positive patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal cortex-predominant [ 18 F]PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD (progressive supranuclear palsy with Richardson syndrome [PSP Richardson syndrome], corticobasal syndrome, and nonfluent-variant primary progressive aphasia) exhibited higher globus pallidus SUVr than did HCs; pallidal retention was highest in the PSP Richardson syndrome group, in whom SUVr was correlated with symptom severity (ρ = 0.53, P = 0.05). At the individual level, only half of PSP Richardson syndrome, corticobasal syndrome, and nonfluent-variant primary progressive aphasia patients had a pallidal SUVr above that of HCs. Temporal SUVr discriminated AD patients from HCs with high accuracy (area under the receiver operating characteristic curve, 0.94 [95% CI, 0.83-1.00]) for all time windows, whereas discrimination between patients with PSP Richardson syndrome and HCs using pallidal SUVr was fair regardless of time window (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.61-0.92] at 30-40 min vs. 0.81 [95% CI, 0.66-0.96] at 50-60 min; P = 0.67). Conclusion: [ 18 F]PI-2620 SUVr shows an intense and consistent signal in AD but lower-intensity, heterogeneous, and rapidly decreasing binding in patients with suspected FTLD. Further work is needed to delineate the substrate of [ 18 F]PI-2620 binding and the usefulness of [ 18 F]PI2620 SUVr quantification outside the AD continuum., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t -tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD ± 8.5) years versus 54.8 (SD ± 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-ε4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline ( P = 0.006) and 46.1% versus 25.4% at last visit ( P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency ( P < 0.001), Trail Making Test Part B ( P < 0.001) and digit span ( P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points ( P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD ± 39.3) pg/ml dominantly inherited versus 296 (SD ± 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels ( P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles; sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design., Competing Interests: J.J.L.-G.’s research is supported by NIH-NIA (K01AG073526), the Alzheimer’s Association (AARFD-21-851415 and SG-20-690363), the Michael J. Fox Foundation (MJFF-020770), the Foundation for Barnes-Jewish Hospital and the McDonnell Academy. A.M.F., PhD, is the Biomarker Core Leader of the DIAN-TU. She is a member of the scientific advisory boards for Roche Diagnostics, Genentech and AbbVie and also consults for Araclon/Grifols, DiademRes, DiamiR and Otsuka Pharmaceuticals. T.L.S.B., MD, PhD, has investigator-initiated research funding from the NIH, the Alzheimer’s Association, the Barnes-Jewish Hospital Foundation and Avid Radiopharmaceuticals. T.L.S.B. participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly and Company, Biogen, Eisai, Jaansen and F. Hoffmann-La Roche, Ltd. She serves as an unpaid consultant to Eisai and Siemens. She is on the Speaker’s Bureau for Biogen. J.C.M., MD, is the Friedman Distinguished Professor of Neurology, Director, Knight ADRC, Associate Director of DIAN and Founding Principal Investigator of DIAN. He is funded by NIH grants # P30 AG066444, P01AG003991, P01AG026276, U19 AG032438 and U19 AG024904. Neither J.C.M. nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. A.J.A., PhD, has served as a consultant for Biogen Inc and H. Lundbeck HS. J.H., PhD, is a paid consultant for F. Hoffmann-La Roche, Ltd., Takeda, and Lundbeck and is on the Data Safety and Monitoring Board for Eisai. J.L., MD, reports speaker fees from Bayer Vital, Biogen and Roche, consulting fees from Axon Neuroscience and Biogen and author fees from Thieme Medical Publishers and W. Kohlhammer GmbH Medical Publishers. In addition, he reports compensation for serving as chief medical officer for MODAG GmbH, is a beneficiary of the phantom share program of MODAG GmbH and is an inventor in a patent ‘Pharmaceutical Composition and Methods of Use’ (EP 22 159 408.8) filed by MODAG GmbH, all activities outside the submitted work. L.I. is currently a full-time employee of Eli Lilly and Company/Avid Radiopharmaceuticals and a minor shareholder of Eli Lilly and Company. His contribution to the work presented in this manuscript was performed while he was affiliated with the University of California San Francisco. G.D.R., MD, receives research support from NIA P30-AG062422, U01-AG057195, R35 AG072362, R56-AG075744, NINDS R21-NS120629, Alzheimer’s Association ZEN-21-848216, American College of Radiology, Rainwater Charitable Foundation, Shenandoah Foundation, Avid Radiopharmaceuticals, Life Molecular Imaging, GE Healthcare and Genentech. He has served as a consultant for Alector, Eli Lilly, Genentech, GE Healthcare, Roche, Johnson & Johnson and Merck. He serves as associate editor for JAMA Neurology. All other authors report no conflict of interest relevant to this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Importance: The neurological substrates of visual artistic creativity (VAC) are unknown. VAC is demonstrated here to occur early in frontotemporal dementia (FTD), and multimodal neuroimaging is used to generate a novel mechanistic hypothesis involving dorsomedial occipital cortex enhancement. These findings may illuminate a novel mechanism underlying human visual creativity., Objective: To determine the anatomical and physiological underpinnings of VAC in FTD., Design, Setting, and Participants: This case-control study analyzed records of 689 patients who met research criteria for an FTD spectrum disorder between 2002 and 2019. Individuals with FTD and emergence of visual artistic creativity (VAC-FTD) were matched to 2 control groups based on demographic and clinical parameters: (1) not visually artistic FTD (NVA-FTD) and (2) healthy controls (HC). Analysis took place between September 2019 to December 2021., Main Outcomes and Measures: Clinical, neuropsychological, genetic, and neuroimaging data were analyzed to characterize VAC-FTD and compare VAC-FTD with control groups., Results: Of 689 patients with FTD, 17 (2.5%) met VAC-FTD inclusion criteria (mean [SD] age, 65 [9.7] years; 10 [58.8%] female). NVA-FTD (n = 51; mean [SD] age, 64.8 [7] years; 25 [49.0%] female) and HC (n = 51; mean [SD] age, 64.5 [7.2] years; 25 [49%] female) groups were well matched to VAC-FTD demographically. Emergence of VAC occurred around the time of onset of symptoms and was disproportionately seen in patients with temporal lobe predominant degeneration (8 of 17 [47.1%]). Atrophy network mapping identified a dorsomedial occipital region whose activity inversely correlated, in healthy brains, with activity in regions found within the patient-specific atrophy patterns in VAC-FTD (17 of 17) and NVA-FTD (45 of 51 [88.2%]). Structural covariance analysis revealed that the volume of this dorsal occipital region was strongly correlated in VAC-FTD, but not in NVA-FTD or HC, with a volume in the primary motor cortex corresponding to the right-hand representation., Conclusions and Relevance: This study generated a novel hypothesis about the mechanisms underlying the emergence of VAC in FTD. These findings suggest that early lesion-induced activation of dorsal visual association areas may predispose some patients to the emergence of VAC under certain environmental or genetic conditions. This work sets the stage for further exploration of enhanced capacities arising early in the course of neurodegeneration.

Background: In Alzheimer's disease (AD), the gradual accumulation of amyloid-β (Aβ) and tau proteins may underlie alterations in empathy., Objective: To assess whether tau aggregation in the medial temporal lobes related to differences in cognitive empathy (the ability to take others' perspectives) and emotional empathy (the ability to experience others' feelings) in AD., Methods: Older adults (n = 105) completed molecular Aβ positron emission tomography (PET) scans. Sixty-eight of the participants (35 women) were Aβ positive and symptomatic with diagnoses of mild cognitive impairment, dementia of the Alzheimer's type, logopenic variant primary progressive aphasia, or posterior cortical atrophy. The remaining 37 (22 women) were asymptomatic Aβ negative healthy older controls. Using the Interpersonal Reactivity Index, we compared current levels of informant-rated cognitive empathy (Perspective-Taking subscale) and emotional empathy (Empathic Concern subscale) in the Aβ positive and negative participants. The Aβ positive participants also underwent molecular tau-PET scans, which were used to investigate whether regional tau burden in the bilateral medial temporal lobes related to empathy., Results: Aβ positive participants had lower perspective-taking and higher empathic concern than Aβ negative healthy controls. Medial temporal tau aggregation in the Aβ positive participants had divergent associations with cognitive and emotional empathy. Whereas greater tau burden in the amygdala predicted lower perspective-taking, greater tau burden in the entorhinal cortex predicted greater empathic concern. Tau burden in the parahippocampal cortex did not predict either form of empathy., Conclusions: Across AD clinical syndromes, medial temporal lobe tau aggregation is associated with lower perspective-taking yet higher empathic concern.

Traumatic encephalopathy syndrome (TES) criteria were developed to aid diagnosis of chronic traumatic encephalopathy (CTE) pathology during life. Interpreting clinical and biomarker findings in patients with TES during life necessitates autopsy-based determination of the neuropathological profile. We report a clinicopathological series of nine patients with previous repetitive head impacts (RHI) classified retrospectively using the recent TES research framework (100% male and white/Caucasian, age at death 49-84) who completed antemortem neuropsychological evaluations, T1-weighted magnetic resonance imaging, diffusion tensor imaging ( n  = 6), (18)F-fluorodeoxyglucose-positron emission tomography ( n  = 5), and plasma measurement of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau ( n  = 8). Autopsies were performed on all patients. Cognitively, low test scores and longitudinal decline were relatively consistent for memory and executive function. Medial temporal lobe atrophy was observed in all nine patients. Poor white matter integrity was consistently found in the fornix. Glucose hypometabolism was most common in the medial temporal lobe and thalamus. Most patients had elevated plasma GFAP, NfL, and total tau at their initial visit and a subset showed longitudinally increasing concentrations. Neuropathologically, five of the nine patients had CTE pathology ( n  = 4 "High CTE"/McKee Stage III-IV, n  = 1 "Low CTE"/McKee Stage I). Primary neuropathological diagnoses (i.e., the disease considered most responsible for observed symptoms) were frontotemporal lobar degeneration ( n  = 2 FTLD-TDP, n  = 1 FTLD-tau), Alzheimer disease ( n  = 3), CTE ( n  = 2), and primary age-related tauopathy ( n  = 1). In addition, hippocampal sclerosis was a common neuropathological comorbidity ( n  = 5) and associated with limbic-predominant TDP-43 proteinopathy ( n  = 4) or FTLD-TDP ( n  = 1). Memory and executive function decline, limbic system brain changes (atrophy, decreased white matter integrity, hypometabolism), and plasma biomarker alterations are common in RHI and TES but may reflect multiple neuropathologies. In particular, the neuropathological differential for patients with RHI or TES presenting with medial temporal atrophy and memory loss should include limbic TDP-43. Researchers and clinicians should be cautious in attributing cognitive, neuroimaging, or other biomarker changes solely to CTE tau pathology based on previous RHI or a TES diagnosis alone.

Introduction: Ethnoracial differences in cerebrospinal fluid (CSF; amyloid beta 42 [Aβ42], total tau [t-tau], phosphorylated tau 181 [p-tau181], and plasma (p-tau181, neurofilament light [NfL]) biomarkers of Alzheimer's disease (AD) are incompletely understood., Methods: We performed cross-sectional analyses with and without adjustment for covariates comparing baseline CSF (Aβ42, t-tau, p-tau181) and plasma (p-tau181, NfL) values in 47 African Americans (AAs) matched to 141 non-Hispanic Whites (NHWs) and 43 Latinos (LAs) matched to 129 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI)., Results: Unadjusted comparisons revealed no significant differences in plasma or CSF biomarkers between AAs and NHWs. A trend toward a lower CSF t-tau and p-tau181 in LAs compared to NHWs was observed, without significant differences in plasma biomarkers. After adjusting for covariates, there were no significant differences in CSF or plasma biomarkers between AAs and NHWs or between LAs and NHWs., Discussion: Plasma and CSF AD biomarkers may perform similarly across diverse populations but future studies in large, diverse cohorts are needed., Competing Interests: GDR receives research support from Avid Radiopharmaceuticals, GE Healthcare, Genentech, and Life Molecular Imaging. He has received consulting fees from Eisai, Genentech, Johnson & Johnson, and Roche. He is an Associate Editor for JAMA Neurology. ALB receives research support from Biogen, Eisai, Regeneron, and Woolsey. In addition, he has participated in unfunded collaborations with Biogen, Eli Lilly, and Novartis and has received consulting fees from AGTC, Alector, Arvinas, AZ Therapeutics, GSK, Humana, Oligomerix, Oscotec, Roche, Stealth Transposon, TrueBinding, and Wave. MRM receives research support from the Genentech health equity fund and is chair of the National Institute on Aging (NIA) AGCD‐4 study section and a board member of the Alzheimer's Association New York chapter. The remaining authors have no declarations of interest., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Frontotemporal dementia encompasses a group of clinical syndromes defined pathologically by degeneration of the frontal and temporal lobes. Historically, these syndromes have been challenging to diagnose, with an average of about three years between the time of symptom onset and the initial evaluation and diagnosis. Research in the field of neuroimaging has revealed numerous biomarkers of the various frontotemporal dementia syndromes, which has provided clinicians with a method of narrowing the differential diagnosis and improving diagnostic accuracy. As such, neuroimaging is considered a core investigative tool in the evaluation of neurodegenerative disorders. Furthermore, patterns of neurodegeneration correlate with the underlying neuropathological substrates of the frontotemporal dementia syndromes, which can aid clinicians in determining the underlying etiology and improve prognostication. This review explores the advancements in neuroimaging and discusses the phenotypic and pathologic features of behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, and nonfluent variant primary progressive aphasia, as seen on structural magnetic resonance imaging and positron emission tomography., (© 2021. The Author(s).)

This article describes the clinical and radiographic findings in a patient with unilateral aggressive condylar resorption that was diagnosed as osteoarthritis. We present a comprehensive documentation of the clinical manifestations, the appearance on conventional and advanced imaging, and the histopathologic findings. We discuss the systematic approach to develop a differential diagnosis, with specific emphasis on osteoarthritis and idiopathic condylar resorption. Finally, we also discuss the factors that play a role in management of this condition.

Objective: The aim of this systematic review was to assess the clinical and imaging findings of keratocystic odontogenic tumor (KOT). This article also attempts to determine the prevalence of KOTs and orthokeratinized odontogenic cyst (OOC) in the western Indian population and to compare demographic and radiographic findings of KOT of our cohort with that of the rest of the world., Study Design: Relevant publications on KOT were reviewed from the published literature from 1976 to March 2012. Data regarding the 72 additional cases from Mumbai also were analyzed., Results: Sixty-five reports were identified for this systematic review. The findings were divided into 4 global groups for analysis. The prevalence of KOT was 0.0173% and that of OOC 0.0012%. Male sex, mandible, and the unilocular variation were predominant for the additional cases., Conclusions: The characterization of the KOT lesions was accomplished, taking into consideration the variations to the western Indian population., (Copyright © 2013 Elsevier Inc. All rights reserved.)