2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Frontotemporal-Lobar-Degeneration

The purpose of this study was to compare the diagnostic accuracy of antemortem. One hundred one participants underwent PIB and FDG PET during life and neuropathological assessment. PET scans were visually interpreted by 3 raters blinded to clinical information. PIB PET was rated as positive or negative for cortical retention, whereas FDG scans were read as showing an Alzheimer disease (AD) or non-AD pattern. Neuropathological diagnoses were assigned using research criteria. Majority visual reads were compared to intermediate-high AD neuropathological change (ADNC).. One hundred one participants were included (mean age = 67.2 years, 41 females, Mini-Mental State Examination = 21.9, PET-to-autopsy interval = 4.4 years). At autopsy, 32 patients showed primary AD, 56 showed non-AD neuropathology (primarily frontotemporal lobar degeneration [FTLD]), and 13 showed mixed AD/FTLD pathology. PIB showed higher sensitivity than FDG for detecting intermediate-high ADNC (96%, 95% confidence interval [CI] = 89-100% vs 80%, 95% CI = 68-92%, p = 0.02), but equivalent specificity (86%, 95% CI = 76-95% vs 84%, 95% CI = 74-93%, p = 0.80). In patients with congruent PIB and FDG reads (77/101), combined sensitivity was 97% (95% CI = 92-100%) and specificity was 98% (95% CI = 93-100%). Nine of 24 patients with incongruent reads were found to have co-occurrence of AD and non-AD pathologies.. In our sample enriched for younger onset cognitive impairment, PIB-PET had higher sensitivity than FDG-PET for intermediate-high ADNC, with similar specificity. When both modalities are congruent, sensitivity and specificity approach 100%, whereas mixed pathology should be considered when PIB and FDG are incongruent. ANN NEUROL 2021;89:389-401.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Autopsy; Brain; DNA-Binding Proteins; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Humans; Male; Middle Aged; Pick Disease of the Brain; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity; tau Proteins; Thiazoles

Rates of amyloid-β (Aβ) accumulation have been characterized across the cognitively normal to typical Alzheimer's dementia spectrum, but little is known about Aβ accumulation in atypical Alzheimer's disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD).. We aimed tocharacterize longitudinal Aβ accumulation anddetermine the influence of age, apolipoprotein E (APOE) genotype, disease duration, and sexin atypical AD and FTLD.. 322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serialPiB-PET scans (42 atypical AD, 31 FTLD). Global Aβ standard uptake value ratios were calculated for every scan. Mixed effects models were used to assess the effect of age, APOE genotype, disease duration, and sex on baseline and change measures of Aβ.. Atypical AD showed higher baseline Aβ than FTLD. Rate of Aβ accumulation was not associated with baseline Aβ in either group. Older age was associated with greater baseline Aβ and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOEɛ4 genotype was associated with greater baseline Aβ in FTLD but did not influence rates of accumulation. Rates of Aβ accumulation were faster in FTLD patents with time from onset-to-PET≤4 years. Female sex was associated with faster rates of accumulation in atypical AD.. Accumulation of Aβ is observed in atypical AD and FTLD, although different demographic factors influence accumulation in these diseases providing insight into potentially different biological mechanisms of Aβ deposition.

Topics: Age of Onset; Aged; Aging; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Apolipoproteins E; Disease Progression; Female; Frontotemporal Lobar Degeneration; Genotype; Humans; Longitudinal Studies; Male; Middle Aged; Positron-Emission Tomography; Sex Characteristics; Thiazoles

In subjects with amyloid deposition, striatal accumulation of. Seventy-three subjects who complained of cognitive disturbance underwent dynamic PiB-PET studies and showed positive PiB accumulation were retrospectively selected. These subjects included 34 AD, 26 mild cognitive impairment, 2 frontotemporal lobar degeneration, 2 Parkinson's disease, 5 dementia with Lewy bodies, and 4 undefined diagnosis patients. Individual BP. There were highly significant correlations between striatal and prefrontal BP. Our study demonstrated positive correlations in amyloid deposits between the striatum and other cortical areas with functional and anatomical links. The amyloid distribution in the brain is not random, but spreads following the functional and anatomical connections.

Topics: Aged; Alzheimer Disease; Amyloid; Aniline Compounds; Cerebral Cortex; Cognitive Dysfunction; Corpus Striatum; Female; Frontotemporal Lobar Degeneration; Humans; Lewy Body Disease; Male; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Thiazoles

Today, ligands that bind to fibrillar β-amyloid are detectable by Positron Emission Tomography (PET) allowing for in vivo visualization for Abeta burden. However, amyloid plaques detection per se does not establish Alzheimer's Disease diagnosis. In this sense, the utility of amyloid imaging to improve clinical diagnosis was settled only for specific clinical scenarios and few studies have assessed amyloid molecular neuroimaging in a broader clinical setting. The aim of this study is to determine the frequency of PiB amyloid findings in different diagnostic syndromes grouped into high and low probability pre- test categories, taking into account pre-test clinical assumption of the presence of AD related pathology.. 144 patients were assigned into categories of high or low pretest probability according to clinical suspicion of AD pathology. The high probability group included: amnestic Mild Cognitive Impairment (MCI), amnestic and other domains MCI, Dementia of Alzheimer's Type (DAT), Posterior Cortical Atrophy (PCA), logopenic Primary Progressive Aphasia (PPA), Cerebral Amyloid Angiopathy and mixed dementia. The low assumption group included: normal controls, non-amnestic MCI, non-logopenic PPA and Frontotemporal Dementia (FTD).. Only normal controls and DAT patients (typical and atypical presentation) were the most consistent across clinical and molecular diagnostics. MCI, non-logopenic PPA and FTD were the syndromic diagnoses that most discrepancies were found.. This study demonstrates that detecting in vivo amyloid plaques by molecular imaging is considerably frequent in most of the dementia syndromes and shows that there are frequent discordance between molecular diagnosis and clinical assumption.

Topics: Aged; Alzheimer Disease; Amnesia; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Benzothiazoles; Cerebral Amyloid Angiopathy; Cerebral Cortex; Cognitive Dysfunction; Dementia; Female; Frontotemporal Lobar Degeneration; Humans; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Thiazoles