2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Frontotemporal-Dementia

To review the rapidly expanding literature of amyloid PET imaging with particular attention to Pittsburgh compound-B (PIB) in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), fronto-temporal dementia (FTD), mild cognitive impairment (MCI) and cognitively normal volunteers.. Literature searches were performed using Medline up to February 2010. Individual articles were then examined for additional references not revealed by automated searches. This yielded 79 articles whose abstracts were read by the authors to select key papers.. Amyloid deposition assessed using PIB-PET is significantly elevated in AD and DLB compared to controls and those with FTD. In MCI, uptake is often intermediate between AD and normal ageing, and excessive amyloid burden in non-demented individuals with MCI are likely to represent high-risk cases. Amyloid deposition appears to be an early event, and as dementia progresses clinical decline seems to be more associated with neurodegeneration than amyloid burden.. PIB-PET imaging is a sensitive and specific marker for underlying Aβ amyloid deposition and represents an important investigative tool for examining the relationship between amyloid burden, clinical symptoms and structural and functional changes in dementia. Amyloid imaging may also be useful for selecting patients for anti-amyloid therapies. However, studies have identified PIB-positive cases in otherwise healthy older individuals (10-30%), limiting diagnostic specificity. Development of biomarkers for investigating other aspects of dementia pathology, i.e. soluble Aβ, tau, synuclein and brain inflammation would further inform our understanding and assist in studying disease-modifying and preventive treatments in dementia.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Biomarkers; Cognition Disorders; Dementia; Frontotemporal Dementia; Humans; Image Processing, Computer-Assisted; Lewy Body Disease; Positron-Emission Tomography; Thiazoles

[(11)C]Pittsburgh compound B ([(11)C]PIB) and [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) PET measure fibrillar amyloid-β load and glucose metabolism, respectively. We evaluated the impact of these tracers on the diagnostic process in a memory clinic population.. One hundred fifty-four patients underwent paired dynamic [(11)C]PIB and static [(18)F]FDG PET scans shortly after completing a standard dementia screening. Two-year clinical follow-up data were available for 39 patients. Parametric PET images were assessed visually and results were reported to the neurologists responsible for the initial diagnosis. Outcome measures were (change in) clinical diagnosis and confidence in that diagnosis before and after disclosing PET results.. [(11)C]PIB scans were positive in 40 of 66 (61%) patients with a clinical diagnosis of Alzheimer's disease (AD), 5 of 18 (28%) patients with frontotemporal dementia (FTD), 4 of 5 (80%) patients with Lewy body dementia, and 3 of 10 (30%) patients with other dementias. [(18)F]FDG uptake patterns matched the clinical diagnosis in 38 of 66 (58%) of AD patients, and in 6 of 18 (33%) FTD patients. PET results led to a change in diagnosis in 35 (23%) patients. This only occurred when prior diagnostic certainty was <90%. Diagnostic confidence increased from 71 ± 17% before to 87 ± 16% after PET (p < .001). Two-year clinical follow-up (n = 39) showed that [(11)C]PIB and [(18)F]FDG predicted progression to AD for patients with mild cognitive impairment, and that the diagnosis of dementia established after PET remained unchanged in 96% of patients.. In a memory clinic setting, combined [(11)C]PIB and [(18)F]FDG PET are of additional value on top of the standard diagnostic work-up, especially when prior diagnostic confidence is low.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Brain; Carbon Radioisotopes; Dementia; Diagnosis, Differential; Disease Progression; Early Diagnosis; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Follow-Up Studies; France; Frontotemporal Dementia; Humans; Lewy Body Disease; Male; Memory Disorders; Middle Aged; Molecular Imaging; Outpatient Clinics, Hospital; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Sensitivity and Specificity; Thiazoles; Treatment Outcome

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

The utility of tau PET imaging in non-Alzheimer's disease (AD) tauopathies like behavioural frontotemporal dementia (bvFTD), which is mainly underlain by TDP-43 or tau pathology, remains debated. We aim to test the hypothesis that [

Topics: Aged; Alzheimer Disease; Aniline Compounds; Aphasia, Primary Progressive; Carbolines; Female; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; tau Proteins; Tauopathies; Thiazoles

We report a diagnostically challenging case of a 64-year-old man with a history of remote head trauma who developed mild behavioral changes and dyscalculia. He was diagnosed with clinical Alzheimer's disease (AD), with additional features consistent with behavioral variant frontotemporal dementia. Structural magnetic resonance imaging revealed atrophy in bilateral frontal and parietal cortices and hippocampi on visual inspection and left frontal pole and bilateral anterior temporal encephalomalacia, suspected to be due to head trauma. Consistent with the diagnosis of Alzheimer's pathology, positron emission tomography (PET) with Pittsburgh compound B suggested the presence of beta-amyloid. Fluorodeoxyglucose PET demonstrated hypometabolism in bilateral frontal and temporoparietal cortices. Voxel-based morphometry showed atrophy predominant in ventral frontal regions (bilateral orbitofrontal cortex, pregenual anterior cingulate/medial superior frontal gyrus), bilateral mid cingulate, bilateral lateral temporal cortex, and posterior insula. Bilateral caudate, thalamus, hippocampi, and cerebellum were prominently atrophied. Unexpectedly, a pathologic hexanucleotide repeat expansion in C9ORF72 was identified in this patient. This report underscores the clinical variability in C9ORF72 expansion carriers and the need to consider mixed pathologies, particularly when imaging studies are inconsistent with a single syndrome or pathology.

Topics: Alzheimer Disease; Aniline Compounds; Apolipoproteins E; Brain; C9orf72 Protein; Carbon Isotopes; Emotions; Fluorodeoxyglucose F18; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Male; Memory; Middle Aged; Mutation; Neuropsychological Tests; Positron-Emission Tomography; Proteins; Social Behavior; Thiazoles; Verbal Learning

Pittsburgh compound B ([11C]-PIB) identifies amyloid-β (Aβ) deposition in vivo. Asymptomatic Aβ deposition has been reported consistently in some healthy older subjects. Of patients with frontotemporal dementia, those who have later onset have a higher potential for Aβ deposition.. Comparison of Aβ deposition in Alzheimer's disease (AD), healthy older controls, and patients with early- and late-onset semantic dementia (SD), a subtype of frontotemporal dementia.. Subjects were recruited from tertiary academic care centers specializing in assessment and management of patients with neurodegenerative disease. We used the radiotracer [11C]-PIB in a high-resolution positron emission tomography scanner to evaluate 11 participants with SD (six with onset before age 65 and five with later onset), 9 with probable AD, and 10 controls over age 60. The main outcome measures were frontal, temporal, parietal, and total [11C]-PIB standardized uptake value ratios to establish PIB-positive (PIB+) cutoff.. The five patients with late-onset SD were PIB-negative. Two of six with early-onset SD, seven of nine with AD, and 1 of 10 controls were PIB+. The SD participants who were PIB+ did not have memory or visuospatial deficits that are typical in AD.. Aβ deposition does not seem to be associated with late-onset SD. Future larger studies might confirm whether a significant minority of early-onset SD patients exhibit Aβ deposition. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Case-Control Studies; Cerebral Cortex; Female; Frontotemporal Dementia; Humans; Male; Middle Aged; Neurodegenerative Diseases; Positron-Emission Tomography; Thiazoles

Alzheimer's disease (AD) and behavioral-variant of frontotemporal dementia (bvFTD) can present with an overlapping neuropsychological profile, which often hinders their clinical differentiation.. To compare changes over time in memory, general cognition tasks, and functional scales between bvFTD and AD.. Consecutive cases diagnosed with probable bvFTD (n = 22) and typical AD (n = 31) with at least two clinical visits were selected. Of these, 13 (9 AD, 4 bvFTD) underwent Pittsburgh compound B PET scan, which supported the clinical diagnosis in all cases. Mixed-model regressions were used to estimate the differential rate of decline on selected tasks between cohorts.. Analyses demonstrated that, despite equivalent baseline performance, bvFTD patients experienced a more rapid functional deterioration and a steeper decline in global cognition than AD patients. At baseline, both groups were impaired on executive function and memory tasks compared to controls, but these deficits were more marked in the bvFTD group. In addition, performance on these domains continued to decline more rapidly in this group.. Neither the initial neuropsychological assessment nor projected performances can reliably distinguish the totality of bvFTD and AD individuals. Nevertheless, annual rates of progression on cognitive tasks provide valuable information and will potentially help establish the impact of future therapeutic treatments in these dementia syndromes.

Topics: Alzheimer Disease; Aniline Compounds; Brain; Diagnosis, Differential; Disease Progression; Executive Function; Female; Follow-Up Studies; Frontotemporal Dementia; Humans; Longitudinal Studies; Male; Memory; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles

This study investigated the improvement in the accuracy of diagnosis of dementia subtypes among Chinese dementia patients who underwent [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) with or without carbon 11-labelled Pittsburgh compound B ((11)C-PIB).. This case series was performed in the Memory Clinic at Queen Mary Hospital, Hong Kong. We reviewed 109 subjects (56.9% were female) who received PET with or without (11)C-PIB between January 2007 and December 2014. Data including age, sex, education level, Mini-Mental State Examination score, Clinical Dementia Rating scale score, neuroimaging report, and pre-/post-imaging clinical diagnoses were collected from medical records. The agreement between the initial and post-PET with or without (11)C-PIB dementia diagnosis was analysed by the Cohen's kappa statistics.. The overall accuracy of initial clinical diagnosis of dementia subtype was 63.7%, and diagnosis was subsequently changed in 36.3% of subjects following PET with or without (11)C-PIB. The rate of accurate initial clinical diagnosis (compared with the final post-imaging diagnosis) was 81.5%, 44.4%, 14.3%, 28.6%, 55.6% and 0% for Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, other dementia, and mixed dementia, respectively. The agreement between the initial and final post-imaging dementia subtype diagnosis was only fair, with a Cohen's kappa of 0.25 (95% confidence interval, 0.05-0.45). For the 21 subjects who underwent (11)C-PIB PET imaging, 19% (n=4) of those with Alzheimer's disease (PIB positive) were initially diagnosed with non-Alzheimer's disease dementia.. In this study, PET with or without (11)C-PIB brain imaging helped improve the accuracy of diagnosis of dementia subtype in 36% of our patients with underlying Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aniline Compounds; Brain; Dementia; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia; Humans; Lewy Body Disease; Male; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Thiazoles

Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate (18)F-THK523 as a potential tau imaging tracer.. Ten healthy elderly controls, three semantic dementia (SD) and ten AD patients underwent neuropsychological examination, MRI as well as (18)F-THK523 and (11)C-Pittsburgh compound B (PIB) positron emission tomography (PET) scans. Composite memory and non-memory scores, global and hippocampal brain volume, and partial volume-corrected tissue ratios for (18)F-THK523 and (11)C-PIB were estimated for all participants. Correlational analyses were performed between global and regional (18)F-THK523, (11)C-PIB, cognition and brain volumetrics.. (18)F-THK523 presented with fast reversible kinetics. Significantly higher (18)F-THK523 retention was observed in the temporal, parietal, orbitofrontal and hippocampi of AD patients when compared to healthy controls and SD patients. White matter retention was significantly higher than grey matter retention in all participants. The pattern of cortical (18)F-THK523 retention did not correlate with Aβ distribution as assessed by (11)C-PIB and followed the known distribution of tau in the AD brain, being higher in temporal and parietal areas than in the frontal region. Unlike (11)C-PIB, hippocampal (18)F-THK523 retention was correlated with several cognitive parameters and with hippocampal atrophy.. (18)F-THK523 does not bind to Aβ in vivo, while following the known distribution of paired helical filaments (PHF)-tau in the brain. Significantly higher cortical (18)F-THK523 retention in AD patients as well as the association of hippocampal (18)F-THK523 retention with cognitive parameters and hippocampal volume suggests (18)F-THK523 selectively binds to tau in AD patients. Unfortunately, the very high (18)F-THK523 retention in white matter precludes simple visual inspection of the images, preventing its use in research or clinical settings.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Case-Control Studies; Female; Frontotemporal Dementia; Humans; Male; Middle Aged; Positron-Emission Tomography; Protein Binding; Quinolines; Radiopharmaceuticals; tau Proteins; Thiazoles; Tissue Distribution

The C9ORF72 hexanucleotide expansion is a major pathological expansion pattern found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (C9FTD/ALS). We describe a patient in whom early clinical evaluation, MRI and fluorodeoxyglucose (FDG) positron emission tomography (PET) findings failed to definitively differentiate between FTD and Alzheimer's disease (AD), whereas (11)C-Pittsburgh compound B (PiB) PET was negative for amyloid pathology. He later developed ALS symptoms, and post mortem neuropathological findings were diagnostic of FTD-ALS, while no findings suggested AD. His sister was diagnosed with FTD, and the C9ORF72 expansion was detected in both siblings. We conclude that ¹¹C-PiB PET imaging may help the early differential diagnosis between AD and FTD, including C9FTD/ALS.

Topics: Amyotrophic Lateral Sclerosis; Aniline Compounds; Brain; C9orf72 Protein; Diagnosis, Differential; DNA Repeat Expansion; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia; Humans; Male; Middle Aged; Neurons; Positron-Emission Tomography; Proteins; Siblings; Thiazoles

The relationship between the apolipoprotein E (ApoE) ε4 genotype and an increased risk of developing Alzheimer's disease (AD) has been well established in Caucasians but is less established among other ethnicities. ApoE ε4 has also been associated with several other neurological disorders. Whether ApoΕ4 ε4 is a risk factor for frontotemporal dementia (FTD) remains controversial. This study examined 432 patients with AD, 62 with FTD, and 381 sex- and age-matched controls. The ApoE ε4 allele frequency was significantly increased among patients in the AD and FTD groups compared with controls. The frequency of the ApoΕ ε4 allele was 24.86% in late-onset AD (p < 0.01), 18.02% in early-onset AD (p < 0.01), 16.13% in FTD (p < 0.01), and 7.34% in controls. ApoΕ ε4 prevalence was similar in the FTD and AD groups. The present study suggests that the ApoE ε4 allele is a risk factor for both disorders.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Apolipoprotein E4; Asian People; China; Diagnostic and Statistical Manual of Mental Disorders; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia; Gene Frequency; Genotype; Humans; Male; Middle Aged; Polymerase Chain Reaction; Positron-Emission Tomography; Radiopharmaceuticals; Risk Factors; Thiazoles; Tomography, X-Ray Computed

We described the cases of two patients with dementia associated with motor neuron disease, the former with frontotemporal dementia (FTD) and the latter with Alzheimer's disease (AD), studied by the Pittsburgh compound B-positron emission tomography (PIB-PET). In the FTD patient, the PIB-PET revealed no amyloid accumulation in the cortex, whilst in the AD patient showed amyloid accumulation mainly in the frontal, parietal and lateral temporal lobes, besides the posterior cingulate gyrus and the precuneus. Thus, PIB-PET might facilitate the discrimination of different proteinopathies that cause neurodegenerative diseases, as dementia associated with ALS.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Brain; Diagnosis, Differential; Female; Frontotemporal Dementia; Humans; Male; Middle Aged; Motor Neuron Disease; Positron-Emission Tomography; Thiazoles

Drawing a clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease (AD) is tricky, particularly at the early stages of disease. This study evaluates the possibility in differentiating 39 FTD, 39 AD, and 39 controls (CTR) by means of power spectral analysis and standardized low resolution brain electromagnetic tomography (sLORETA) within delta, theta, alpha 1 and 2, beta 1, 2, and 3 frequency bands. Both analyses revealed in AD patients, relative to CTR, higher expression of diffuse delta/theta and lower central/posterior fast frequency (from alpha1 to beta2) bands. FTD patients showed diffuse increased theta power compared with CTR and lower delta relative to AD patients. Compared with FTD, AD patients showed diffuse higher theta power at spectral analysis and, at sLORETA, decreased alpha2 and beta1 values in central/temporal regions. Spectral analysis and sLORETA provided complementary information that might help characterizing different patterns of electroencephalogram (EEG) oscillatory activity in AD and FTD. Nevertheless, this differentiation was possible only at the group level because single patients could not be discerned with sufficient accuracy.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Diagnosis, Differential; Electroencephalography; Female; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Neuropsychological Tests; Positron-Emission Tomography; Radiopharmaceuticals; Thiazoles; Tomography, X-Ray Computed

The development of imaging reagents is of considerable interest in the Alzheimer's disease (AD) field. Some of these, such as Pittsburgh Compound B (PiB), were designed to bind to the amyloid-β peptide (Aβ), the major component of amyloid deposits in the AD brain. Although these agents were designed for imaging amyloid deposits in vivo, a major avenue of evaluation relies on postmortem cross validation with established indices of AD pathology. In this study, we evaluated changes in the postmortem binding of PiB and its relationship to other aspects of Aβ-related pathology in a series of AD cases and age-matched controls. We also examined cases of preclinical AD (PCAD) and amnestic mild cognitive impairment (MCI), both considered early points in the AD continuum. PiB binding was found to increase with the progression of the disease and paralleled increases in the less soluble forms of Aβ, including SDS-stable Aβ oligomers. Increased PiB binding and its relationship to Aβ was only significant in a brain region vulnerable to the development of AD pathology (the superior and middle temporal gyri) but not in an unaffected region (cerebellum). This implies that the amyloid deposited in disease-affected regions may possess fundamental, brain region specific characteristics that may not as yet be fully appreciated. These data support the idea that PiB is a useful diagnostic tool for AD, particularly in the early stage of the disease, and also show that PiB could be a useful agent for the discovery of novel disease-related properties of amyloid.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Aniline Compounds; Brain; Cognitive Dysfunction; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Frontotemporal Dementia; Humans; Male; Neuropsychological Tests; Organ Size; Positron-Emission Tomography; Thiazoles

The International Consensus Criteria for the diagnosis of primary progressive aphasia (PPA; Gorno-Tempini et al., 2011) propose apraxia of speech (AOS) as 1 of 2 core features of nonfluent/agrammatic PPA and propose phonological errors or absence of motor speech disorder as features of logopenic PPA. We investigated the sensitivity and specificity of AOS and phonological errors as markers for these variants and also investigated the relationship between AOS, phonological errors, and findings on C-labeled Pittsburgh Compound B (PiB)-positron emission tomography (PET) imaging associated with putative Alzheimer-type pathology.. Connected speech and word repetition in 23 people with PPA who underwent PiB-PET imaging were rated for apraxic versus phonological disruption by 1 rater who was blind to diagnosis and by 2 raters who were blind to PiB-PET results.. Apraxic characteristics had high sensitivity for nonfluent/agrammatic PPA, and phonological errors had high sensitivity for logopenic PPA; however, phonological errors showed lower specificity for logopenic PPA. On PiB imaging, 8 of 9 people with predominant AOS returned negative results, whereas participants with no or questionable AOS with and without phonological errors returned positive results.. Attention to AOS and phonological errors may help counter some of the inherent limitations of diagnosis-by-exclusion in the current International Consensus Criteria for diagnosing PPA.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Aphasia, Broca; Apraxias; Carbon Radioisotopes; Diagnosis, Differential; Female; Frontotemporal Dementia; Humans; Male; Middle Aged; Phonation; Phonetics; Positron-Emission Tomography; Primary Progressive Nonfluent Aphasia; Psycholinguistics; Thiazoles

The availability of new PET ligands offers the potential to measure fibrillar β-amyloid in the brain. Nevertheless, physiologic information in the form of perfusion or metabolism may still be useful in differentiating causes of dementia during life. In this study, we investigated whether early (11)C-Pittsburgh compound B ((11)C-PIB) PET frames (perfusion (11)C-PIB [pPIB]) could provide information equivalent to blood flow and metabolism. First, we assessed the similarity of pPIB and (18)F-FDG PET images in a test cohort with various clinical diagnoses (n = 10), and then we validated the results in a cohort of patients with Alzheimer disease (AD) (n = 42; mean age ± SD, 66.6 ± 10.6 y; mean Mini-Mental State Examination [MMSE] score ± SD, 22.2 ± 6.0) or frontotemporal lobar degeneration (FTLD) (n = 31; age ± SD, 63.9 ± 7.1 y, mean MMSE score ± SD, 23.8 ± 6.7).. To identify the (11)C-PIB frames best representing perfusion, we ran on a test cohort an iterative algorithm, including generating normalized (cerebellar reference) perfusion pPIB images across variable frame ranges and calculating Pearson R values of the sum of these pPIB frames with the sum of all (18)F-FDG frames (cerebellar normalized) for all brain tissue voxels. Once this perfusion frame range was determined on the test cohort, it was then validated on an extended cohort and the power of pPIB in differential diagnosis was compared with (18)F-FDG by performing a logistic regression of regions-of-interest tracer measure (pPIB or (18)F-FDG) versus diagnosis.. A 7-min window, corresponding to minutes 1-8 (frames 5-15), produced the highest voxelwise correlation between (18)F-FDG and pPIB (R = 0.78 ± 0.05). This pPIB frame range was further validated on the extended AD and FTLD cohort across 12 regions of interest (R = 0.91 ± 0.09). A logistic model using pPIB was able to classify 90.5% of the AD and 83.9% of the FTLD patients correctly. Using (18)F-FDG, we correctly classified 88.1% of AD and 83.9% of FTLD patients. The temporal pole and temporal neocortex were significant discriminators (P < 0.05) in both models, whereas in the model with pPIB the frontal region was also significant.. The high correlation between pPIB and (18)F-FDG measures and their comparable performance in differential diagnosis are promising in providing functional information using (11)C-PIB PET data. This approach could be useful, obviating (18)F-FDG scans when longer-lived amyloid imaging agents become available.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Benzothiazoles; Cohort Studies; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia; Humans; Logistic Models; Male; Middle Aged; Models, Statistical; Neuropsychological Tests; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Thiazoles; Time Factors