Pittsburgh Compound B Distribution Volume Ratio Research Articles

Associations between regional blood-brain barrier permeability, aging, and Alzheimer's disease biomarkers in cognitively normal older adults.

Increased blood-brain barrier permeability (BBBp) has been hypothesized as a feature of aging that may lead to the development of Alzheimer's disease (AD). We sought to identify the brain regions most vulnerable to greater BBBp during aging and examine their regional relationship with neuroimaging biomarkers of AD. We studied 31 cognitively normal older adults (OA) and 10 young adults (YA) from the Berkeley Aging Cohort Study (BACS). Both OA and YA received dynamic contrast-enhanced MRI (DCE-MRI) to quantify Ktrans values, as a measure of BBBp, in 37 brain regions across the cortex. The OA also received Pittsburgh compound B (PiB)-PET to create distribution volume ratios (DVR) images and flortaucipir (FTP)- PET to create partial volume corrected standardized uptake volume ratios (SUVR) images. Repeated measures ANOVA assessed the brain regions where OA showed greater BBBp than YA. In OA, Ktrans values were compared based on sex, Aβ positivity status, and APOE4 carrier status within a composite region across the areas susceptible to aging. We used linear models and sparse canonical correlation analysis (SCCA) to examine the relationship between Ktrans and AD biomarkers. OA showed greater BBBp than YA predominately in the temporal lobe, with some involvement of parietal, occipital and frontal lobes. Within an averaged ROI of affected regions, there was no difference in Ktrans values based on sex or Aβ positivity, but OA who were APOE4 carriers had significantly higher Ktrans values. There was no direct relationship between averaged Ktrans and global Aβ pathology, but there was a trend for an Ab status by tau interaction on Ktrans in this region. SCCA showed increased Ktrans was associated with increased PiB DVR, mainly in temporal and parietal brain regions. There was not a significant relationship between Ktrans and FTP SUVR. Our findings indicate that the BBB shows regional vulnerability during normal aging that overlaps considerably with the pattern of AD pathology. Greater BBBp in brain regions affected in aging is related to APOE genotype and may also be related to the pathological accumulation of Aβ.

Harnessing cognitive trajectory clusterings to examine subclinical decline risk factors.

Cognitive decline in Alzheimer's disease and other dementias typically begins long before clinical impairment. Identifying people experiencing subclinical decline may facilitate earlier intervention. This study developed cognitive trajectory clusters using longitudinally based random slope and change point parameter estimates from a Preclinical Alzheimer's disease Cognitive Composite and examined how baseline and most recently available clinical/health-related characteristics, cognitive statuses and biomarkers for Alzheimer's disease and vascular disease varied across these cognitive clusters. Data were drawn from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal cohort study of adults from late midlife, enriched for a parental history of Alzheimer's disease and without dementia at baseline. Participants who were cognitively unimpaired at the baseline visit with ≥3 cognitive visits were included in trajectory modelling (n = 1068). The following biomarker data were available for subsets: positron emission tomography amyloid (amyloid: n = 367; [11C]Pittsburgh compound B (PiB): global PiB distribution volume ratio); positron emission tomography tau (tau: n = 321; [18F]MK-6240: primary regions of interest meta-temporal composite); MRI neurodegeneration (neurodegeneration: n = 581; hippocampal volume and global brain atrophy); T2 fluid-attenuated inversion recovery MRI white matter ischaemic lesion volumes (vascular: white matter hyperintensities; n = 419); and plasma pTau217 (n = 165). Posterior median estimate person-level change points, slopes' pre- and post-change point and estimated outcome (intercepts) at change point for cognitive composite were extracted from Bayesian Bent-Line Regression modelling and used to characterize cognitive trajectory groups (K-means clustering). A common method was used to identify amyloid/tau/neurodegeneration/vascular biomarker thresholds. We compared demographics, last visit cognitive status, health-related factors and amyloid/tau/neurodegeneration/vascular biomarkers across the cognitive groups using ANOVA, Kruskal-Wallis, χ2, and Fisher's exact tests. Mean (standard deviation) baseline and last cognitive assessment ages were 58.4 (6.4) and 66.6 (6.6) years, respectively. Cluster analysis identified three cognitive trajectory groups representing steep, n = 77 (7.2%); intermediate, n = 446 (41.8%); and minimal, n = 545 (51.0%) cognitive decline. The steep decline group was older, had more females, APOE e4 carriers and mild cognitive impairment/dementia at last visit; it also showed worse self-reported general health-related and vascular risk factors and higher amyloid, tau, neurodegeneration and white matter hyperintensity positive proportions at last visit. Subtle cognitive decline was consistently evident in the steep decline group and was associated with generally worse health. In addition, cognitive trajectory groups differed on aetiology-informative biomarkers and risk factors, suggesting an intimate link between preclinical cognitive patterns and amyloid/tau/neurodegeneration/vascular biomarker differences in late middle-aged adults. The result explains some of the heterogeneity in cognitive performance within cognitively unimpaired late middle-aged adults.

Amyloid plaque burden and dual tasking impairments on the Timed up and go test in Parkinson disease (P5-11.006)

<h3>Objective:</h3> Dual tasking (DT) impairments in Parkinson disease (PD) are a correlate of fall risk. Their biological basis may reflect multiple underlying pathological causes. <h3>Background:</h3> Low-level amyloid-beta (Abeta) plaque burden is known to correlate with gait and cognitive impairments in PD. It is possible that Abeta plaque burden may exacerbate fall risk by worsening dual tasking cost, though this has not been evaluated to date. <h3>Design/Methods:</h3> In a cross-sectional cohort of 20 participants with PD, we explored the association between Abeta plaque burden and dual task cost (DTC) on the timed up and go test (TUG). TUG gait parameters were assessed using Ambulatory Parkinson’s disease monitoring (APDM) OPAL wearable sensors. Baseline TUG testing was followed by TUG testing during which the participant performed a cognitive task. DTC was calculated as the percentage difference in seconds between the two tasks. Regional Abeta plaque burden was assessed by [11C]Pittsburgh compound B (PiB) positron emission tomography (PET) imaging. Bivariate Pearson’s r statistic was calculated between DTC and PiB distribution volume ratio (DVR) in different regions of interest. <h3>Results:</h3> DTC during the TUG show no significant correlations with PiB DVR in the total cortical mantle (r=0.061, p=0.797), visuospatial cortex (r=0.061, p=0.798), striatum (r=0.033, p=0.890), or thalamus (r=0.041, p=0.865) but did correlate with elevated PiB DVR in the substantia nigra (r=0.535, p=0.015). <h3>Conclusions:</h3> DTC in PD does not correlate with supratentorial amyloid plaque burden but may reflect mixed neurodegenerative pathology, including Abeta plaque burden, in the substantia nigra. <b>Disclosure:</b> Ms. Harrie has nothing to disclose. The institution of Dr. Hampstead has received research support from NIH. The institution of Dr. Hampstead has received research support from Department of Veterans Affairs. Dr. Hampstead has received intellectual property interests from a discovery or technology relating to health care. Dr. Hampstead has received publishing royalties from a publication relating to health care. Catherine Lewis has nothing to disclose. Ms. Herreshoff has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Huxley Medical Inc. Dr. Kotagal has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders Society. The institution of Dr. Kotagal has received research support from NIH. The institution of Dr. Kotagal has received research support from VA Healthcare System.

PIB‐PET perfusion and FDG‐PET are highly correlated and similarly associated with cognitive performance

AbstractBackgroundFluorodeoxyglucose PET is a useful measure of neurodegeneration in Alzheimer’s disease and aging. Because glucose metabolism and cerebral blood flow are coupled, PET measures of perfusion also detect neurodegeneration. Dynamic PET data obtained immediately following injection of highly extracted tracers can estimate relative perfusion (R1). We performed this study to examine R1 in relation to FDG PET for detection of AD and relationships to cognition.MethodDynamic Pittsburgh compound B (PIB) PET (0‐90 min) and FDG‐PET (30‐60 min) scans were collected in cognitively normal (CN) participants (N=109, mean age 76.2±6.4 years) and Aβ‐positive patients with MCI or dementia (N=85, mean age 65.1±9.6 years). The Simplified Reference Tissue Model 2 estimated R1 and PIB distribution volume ratios, the latter used to dichotomize CN participants by amyloid status (68 Aβ‐, 41 Aβ+). We used a standard “metaROI” composed of FreeSurfer (Desikan‐Killiany) ‐based ROIs in temporal, parietal and cingulate cortex to quantify R1 and FDG in all participants to compare R1 and FDG in the detection of between‐group differences with a one‐way ANOVA, and classification of participants with logistic regression models. Relationships between R1 or FDG and dementia severity, measured as the CDR sum of boxes, were examined in clinically impaired patients in multiple FreeSurfer‐based regions of interest.ResultR1 and FDG were both significantly lower in patients than in CN groups (R1: F(2,191) = 70.5, p&lt;0.000001; FDG: F(2,191) = 87.9, p&lt;0.000001), which did not differ significantly (Figure 1). FDG and R1 were both able to distinguish between patients and CN participants similarly, with sensitivity and specificity ranging from 80‐86% (Figure 2). R1 and FDG were associated with CDR sum of boxes in a similar set of frontal, temporal, and parietal regions, although FDG associations were stronger and more extensive (Figure 3).ConclusionR1 and FDG perform similarly in differentiating dementia patients and controls. Relationships between FDG/R1 and cognitive performance are similar, although FDG shows more extensive associations. R1 measures obtained from dynamic PIB‐PET scans are useful indicators of neurodegeneration which can substitute for FDG in many situations.

PIB‐PET perfusion and FDG‐PET are highly correlated and similarly associated with cognitive performance

AbstractBackgroundFluorodeoxyglucose PET is a useful measure of neurodegeneration in Alzheimer’s disease and aging. Because glucose metabolism and cerebral blood flow are coupled, PET measures of perfusion also detect neurodegeneration. Dynamic PET data obtained immediately following injection of highly extracted tracers can estimate relative perfusion (R1). We performed this study to examine R1 in relation to FDG PET for detection of AD and relationships to cognition.MethodDynamic Pittsburgh compound B (PIB) PET (0‐90 min) and FDG‐PET (30‐60 min) scans were collected in cognitively normal (CN) participants (N=109, mean age 76.2±6.4 years) and Aβ‐positive patients with MCI or dementia (N=85, mean age 65.1±9.6 years). The Simplified Reference Tissue Model 2 estimated R1 and PIB distribution volume ratios, the latter used to dichotomize CN participants by amyloid status (68 Aβ‐, 41 Aβ+). We used a standard “metaROI” composed of FreeSurfer (Desikan‐Killiany) ‐based ROIs in temporal, parietal and cingulate cortex to quantify R1 and FDG in all participants to compare R1 and FDG in the detection of between‐group differences with a one‐way ANOVA, and classification of participants with logistic regression models. Relationships between R1 or FDG and dementia severity, measured as the CDR sum of boxes, were examined in clinically impaired patients in multiple FreeSurfer‐based regions of interest.ResultR1 and FDG were both significantly lower in patients than in CN groups (R1: F(2,191) = 70.5, p&lt;0.000001; FDG: F(2,191) = 87.9, p&lt;0.000001), which did not differ significantly (Figure 1). FDG and R1 were both able to distinguish between patients and CN participants similarly, with sensitivity and specificity ranging from 80‐86% (Figure 2). R1 and FDG were associated with CDR sum of boxes in a similar set of frontal, temporal, and parietal regions, although FDG associations were stronger and more extensive (Figure 3).ConclusionR1 and FDG perform similarly in differentiating dementia patients and controls. Relationships between FDG/R1 and cognitive performance are similar, although FDG shows more extensive associations. R1 measures obtained from dynamic PIB‐PET scans are useful indicators of neurodegeneration which can substitute for FDG in many situations.

Conscientiousness is associated with less amyloid deposition in cognitively normal aging.

Little is known about the association between personality and Alzheimer's disease (AD) biomarkers, and existing results are inconsistent. We aimed to determine whether personality was associated with β-amyloid (Aβ) accumulation in cognitively normal aging. One hundred twenty-nine participants were included in this cross-sectional study. Personality was measured with the Big Five Inventory (BFI) and brain Aβ deposition was assessed with [11C] Pittsburgh compound B (PiB)-positron emission tomography (PET) imaging. Conscientiousness scores had a negative association with global PiB distribution volume ratio (DVR) in all participants after adjusting for age, sex, education, and vascular risk factors (β[SE] = -0.19[0.09], 95% confidence interval [CI: -0.35, -0.02], p = .031), while agreeableness, extraversion, neuroticism, and openness had no association with global PiB DVR. Assuming the relative stability of personality traits, these findings suggest that conscientiousness may protect against Aβ accumulation in cognitively normal aging through mechanisms that are as yet unknown. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Interaction Between Neuroinflammation and β-Amyloid in Cognitive Decline in Parkinson's Disease.

Activated microglia have been reported to play an important role in Parkinson's disease (PD). A more rapid cognitive decline has been associated with deposits of β-amyloid. In this study, the aim was to evaluate the role of brain β-amyloid and its relationship with activated microglia in PD patients with normal and impaired cognition. We studied 17 PD patients with normal cognition (PDn), 12 PD patients with mild cognitive impairment (PD-MCI), and 12 healthy controls (HCs) with [11C] Pittsburgh compound B (PIB) to assess the impact of β-amyloid deposition in the brain on microglial activation evaluated using the translocator protein 18-kDa (TSPO) radioligand [18F]-FEPPA. [11C] PIB distribution volume ratio was measured in cortical and subcortical regions. [18F]-FEPPA total distribution volume values were compared for each brain region between groups to evaluate the effect of PIB positivity while adjusting for the TSPO rs6971 polymorphism. Factorial analysis of variance revealed a significant main effect of PIB positivity in the frontal lobe (F(1, 34) = 7.1, p = 0.012). Besides the frontal (p = 0.006) and temporal lobe (p = 0.001), the striatum (p = 0.018), the precuneus (p = 0.019), and the dorsolateral prefrontal cortex (p = 0.010) showed significant group × PIB positivity interaction effects. In these regions, PD-MCIs had significantly higher FEPPA VT if PIB-positive. Our results indicate an interaction between amyloid-β deposition and microglial activation in PD. Further investigations are necessary to evaluate if amyloid deposits cause neuroinflammation and further neurodegeneration or if increased microglia activation develops as a protective response.

Increased radioligand binding to translocator protein correlates with worsened clinical severity and atrophy in Alzheimer's disease

We previously demonstrated that radioligand binding to the 18 kDa translocator protein (TSPO), a marker for inflammation, was greater in patients with Alzheimer's disease (AD) than controls and correlated with clinical severity. We sought to determine the relationship between TSPO binding and progression of AD in a longitudinal study. Eleven patients with either AD or mild cognitive impairment and 8 age-matched controls underwent TSPO PET imaging with 11C-PBR28 at baseline and again after median follow up of 2.7 years. MRI, Pittsburgh Compound B (PIB) PET, and cognitive testing were also performed at baseline and follow up. PET images were corrected for partial volume effects. Regional 11C-PBR28 standardized uptake value ratios were determined using cerebellum as pseudo-reference region. PIB distribution volume ratios were determined using Logan graphical method with cerebellar reference. Among patients, there was a significant correlation between increase in 11C-PBR28 binding and a decline in raw scores on Block Design, Trail Making part B, and Boston Naming Test. The strongest of such correlations occurred in prefrontal and parietal cortices (R > 0.68, P < 0.03). Percent change in 11C-PBR28 binding negatively correlated with %change in voxel count in prefrontal, parietal, and temporal cortices (R < -0.52, P < 0.03). Percent change in 11C-PBR28 correlated with %change in PIB binding in occipital cortex only (R = 0.63, P = 0.037). Controls showed no correlation between 11C-PBR28 binding and brain atrophy. Among patients, ApoE4 carriers (n = 7) had greater increase in 11C-PBR28 binding than non-carriers (n = 4) in inferior temporal cortex (P = 0.042, Mann-Whitney U Test). TSPO increases with worsening clinical severity and cortical atrophy in AD. Larger studies are needed to better determine the relationship between TSPO, fibrillary amyloid load, and ApoE genotype. 11C-PBR28 PET has promise for monitoring AD progression.

Divergent pattern of changes in astrocytosis and fibrillar amyloid plaques as measured by PET in autosomal-dominant and sporadic Alzheimer’s disease

Background: We previously demonstrated that radioligand binding to the 18 kDa translocator protein (TSPO), a marker for inflammation, was greater in patients with Alzheimer’s disease (AD) than controls and correlated with clinical severity. We sought to determine the relationship between TSPO binding and progression of AD in a longitudinal study. Methods: Eleven patients with either AD or mild cognitive impairment and 8 age-matched controls underwent TSPO PET imaging with C-PBR28 at baseline and again after median follow up of 2.7 years. MRI, Pittsburgh Compound B (PIB) PET, and cognitive testing were also performed at baseline and follow up. PET images were corrected for partial volume effects. Regional C-PBR28 standardized uptake value ratios were determined using cerebellum as pseudo-reference region. PIB distribution volume ratios were determined using Logan graphical method with cerebellar reference. Results: Among patients, there was a significant correlation between increase in C-PBR28 binding and a decline in raw scores on Block Design, Trail Making part B, and Boston Naming Test. The strongest of such correlations occurred in prefrontal and parietal cortices (R > 0.68, P < 0.03). Percent change in C-PBR28 binding negatively correlated with %change in voxel count in prefrontal, parietal, and temporal cortices (R< -0.52, P< 0.03). Percent change in C-PBR28 correlated with %change in PIB binding in occipital cortex only (R 1⁄4 0.63, P 1⁄4 0.037). Controls showed no correlation between C-PBR28 binding and brain atrophy. Among patients, ApoE4 carriers (n 1⁄4 7) had greater increase in C-PBR28 binding than noncarriers (n1⁄4 4) in inferior temporal cortex (P1⁄4 0.042, Mann-Whitney U Test). Conclusions:TSPO increases with worsening clinical severity and cortical atrophy in AD. Larger studies are needed to better determine the relationship between TSPO, fibrillary amyloid load, and ApoE genotype. C-PBR28 PET has promise for monitoring AD progression.

Insulin resistance predicts brain amyloid deposition in late middle-aged adults

BackgroundInsulin resistance (IR) increases Alzheimer's disease (AD) risk. IR is related to greater amyloid burden post-mortem and increased deposition within areas affected by early AD. No studies have examined if IR is associated with an in vivo index of amyloid in the human brain in late middle-aged participants at risk for AD. MethodsAsymptomatic, late middle-aged adults (N = 186) from the Wisconsin Registry for Alzheimer's Prevention underwent [C-11]Pittsburgh compound B (PiB) positron emission tomography. The cross-sectional design tested the interaction between insulin resistance and glycemic status on PiB distribution volume ratio in three regions of interest (frontal, parietal, and temporal). ResultsIn participants with normoglycemia but not hyperglycemia, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas, reflecting increased amyloid deposition. ConclusionsThis is the first human study to demonstrate that insulin resistance may contribute to amyloid deposition in brain regions affected by AD.

18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer’s disease

The aim was to identify the amyloid beta (Aβ) deposition by positron emission tomography (PET) imaging with the (18)F-labeled Pittsburgh compound B (PIB) derivative [(18)F]flutemetamol (FMM) across a spectrum of Alzheimer's disease (AD) and to compare Aβ deposition between [(18)F]FMM and [(11)C]PIB PET imaging. The study included 36 patients with AD, 68 subjects with mild cognitive impairment (MCI), 41 older healthy controls (HC) (aged ≥56), 11 young HC (aged ≤45), and 10 transitional HC (aged 46-55). All 166 subjects underwent 30-min static [(18)F]FMM PET 85 min after injection, 60-min dynamic [(11)C]PIB PET, and cognitive testing. [(18)F]FMM scans were assessed visually, and standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest identified on coregistered MRI (cerebellar cortex as a reference region). The PIB distribution volume ratios (DVR) were determined in the same regions. Of 36 AD patients, 35 had positive scans, while 36 of 41 older HC subjects had negative scans. [(18)F]FMM scans had a sensitivity of 97.2% and specificity of 85.3% in distinguishing AD patients from older HC subjects, and a specificity of 100% for young and transitional HC subjects. The [(11)C]PIB scan had the same results. Interreader agreement was excellent (kappa score = 0.81). The cortical FMM SUVR in AD patients was significantly greater than in older HC subjects (1.76 ± 0.23 vs 1.30 ± 0.26, p < 0.01). Of the MCI patients, 68 had a bimodal distribution of SUVR, and 29 of them (42.6%) had positive scans. Cortical FMM SUVR values were strongly correlated with PIB DVR (r = 0.94, n = 145, p < 0.001). [(18)F]FMM PET imaging detects Aβ deposition in patients along the continuum from normal cognitive status to dementia of AD and discriminates AD patients from HC subjects, similar to [(11)C]PIB PET.

Fibrillar amyloid correlates of preclinical cognitive decline

BackgroundIt is not known whether preclinical cognitive decline is associated with fibrillar β-amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status. MethodsFrom a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral-to-cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden. ResultsAt P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners. ConclusionsAsymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.

Blood pressure is associated with higher brain amyloid burden and lower glucose metabolism in healthy late middle-age persons

Epidemiological studies suggest that elevated blood pressure (BP) in midlife is associated with increased risk of Alzheimer's disease (AD) in late life. In this preliminary study, we investigated the extent to which BP measurements are related to positron emission tomography (PET) measurements of fibrillar amyloid-beta burden using Pittsburgh Compound-B (PiB) and fluorodeoxyglucose (FDG) PET measures of cerebral metabolic rate for glucose metabolism (CMRgl) in cognitively normal, late middle-aged to older adult apolipoprotein E (APOE) ε4 homozygotes, heterozygotes and noncarriers. PiB PET results revealed that systolic BP (SBP) and pulse pressure (PP) were each positively correlated with cerebral-to-cerebellar PiB distribution volume ratio (DVR) in frontal, temporal, and posterior-cingulate/precuneus regions, whereas no significant positive correlations were found between PiB distribution volume ratios and diastolic BP (DBP). FDG PET results revealed significant inverse correlations between each of the BP measures and lower glucose metabolism in frontal and temporal brain regions. These preliminary findings provide additional evidence that higher BP, likely a reflection of arterial stiffness, during late midlife may be associated with increased risk of presymptomatic AD.

Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution

Patients with posterior cortical atrophy (PCA) often have Alzheimer disease (AD) at autopsy, yet are cognitively and anatomically distinct from patients with clinical AD. We sought to compare the distribution of β-amyloid and glucose metabolism in PCA and AD in vivo using Pittsburgh compound B (PiB) and FDG-PET. Patients with PCA (n = 12, age 57.5 ± 7.4, Mini-Mental State Examination [MMSE] 22.2 ± 5.1), AD (n = 14, age 58.8 ± 9.6, MMSE 23.8 ± 6.7), and cognitively normal controls (NC, n = 30, age 73.6 ± 6.4) underwent PiB and FDG-PET. Group differences in PiB distribution volume ratios (DVR, cerebellar reference) and FDG uptake (pons-averaged) were assessed on a voxel-wise basis and by comparing binding in regions of interest (ROIs). Compared to NC, both patients with AD and patients with PCA showed diffuse PiB uptake throughout frontal, temporoparietal, and occipital cortex (p < 0.0001). There were no regional differences in PiB binding between PCA and AD even after correcting for atrophy. FDG patterns in PCA and AD were distinct: while both groups showed hypometabolism compared to NC in temporoparietal cortex and precuneus/posterior cingulate, patients with PCA further showed hypometabolism in inferior occipitotemporal cortex compared to both NC and patients with AD (p < 0.05). Patients with AD did not show areas of relative hypometabolism compared to PCA. Fibrillar amyloid deposition in PCA is diffuse and similar to AD, while glucose hypometabolism extends more posteriorly into occipital cortex. Further studies are needed to determine the mechanisms of selective network degeneration in focal variants of AD.

Imaging amyloid deposition in Lewy body diseases.

Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD). To determine whether amyloid deposition, as assessed by PET imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features. Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio. Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function. Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that beta-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

Imaging β-amyloid burden in aging and dementia

To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio. Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus/posterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.