Browsing by Author "Marcus, Daniel S."
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Item Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease(American Academy of Neurology, 2015-09) Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N. N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Benzinger, Tammie L. S.; Bateman, Randall J.; Department of Neurology, IU School of MedicineOBJECTIVE: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). METHODS: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. RESULTS: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. CONCLUSIONS: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials.Item Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease(Wiley, 2022-10) Buckles, Virginia D.; Xiong , Chengjie; Bateman, Randall J.; Hassenstab, Jason; Allegri, Ricardo; Berman, Sarah B.; Chhatwal, Jasmeer P.; Danek, Adrian; Fagan, Anne M.; Ghetti, Bernardino; Goate, Alison; Graff-Radford, Neill; Jucker, Mathias; Levin, Johannes; Marcus, Daniel S.; Masters, Colin L.; McCue, Lena; McDade, Eric; Mori, Hiroshi; Moulder, Krista L.; Noble, James M.; Paumier , Katrina; Preische, Oliver; Ringman, John M.; Fox, Nick C.; Salloway, Stephen; Schofield, Peter R.; Martins, Ralph; Vöglein, Jonathan; Morris, John C.; Dominantly Inherited Alzheimer Network; Pathology and Laboratory Medicine, School of MedicineAs prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n=310) and autopsy-confirmed LOAD participants (n=163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.Item Early behavioural changes in familial Alzheimer's disease in the Dominantly Inherited Alzheimer Network(Oxford University Press, 2015-04) Ringman, John M.; Liang, Li-Jung; Zhou, Yan; Vangala, Sitaram; Teng, Edmond; Kremen, Sarah; Wharton, David; Goate, Alison; Marcus, Daniel S.; Farlow, Martin R.; Ghetti, Bernardino; McDade, Eric; Masters, Colin L.; Mayeux, Richard P.; Rossor, Martin N.; Salloway, Stephen; Schofield, Peter R.; Cummings, Jeffrey L.; Buckles, Virginia; Bateman, Randall J.; Morris, John C.; Dominantly Inherited Alzheimer Network; Department of Neurology, IU School of MedicinePrior studies indicate psychiatric symptoms such as depression, apathy and anxiety are risk factors for or prodromal symptoms of incipient Alzheimer's disease. The study of persons at 50% risk for inheriting autosomal dominant Alzheimer's disease mutations allows characterization of these symptoms before progressive decline in a population destined to develop illness. We sought to characterize early behavioural features in carriers of autosomal dominant Alzheimer's disease mutations. Two hundred and sixty-one persons unaware of their mutation status enrolled in the Dominantly Inherited Alzheimer Network, a study of persons with or at-risk for autosomal dominant Alzheimer's disease, were evaluated with the Neuropsychiatric Inventory-Questionnaire, the 15-item Geriatric Depression Scale and the Clinical Dementia Rating Scale (CDR). Ninety-seven asymptomatic (CDR = 0), 25 mildly symptomatic (CDR = 0.5), and 33 overtly affected (CDR > 0.5) autosomal dominant Alzheimer's disease mutation carriers were compared to 106 non-carriers with regard to frequency of behavioural symptoms on the Neuropsychiatric Inventory-Questionnaire and severity of depressive symptoms on the Geriatric Depression Scale using generalized linear regression models with appropriate distributions and link functions. Results from the adjusted analyses indicated that depressive symptoms on the Neuropsychiatric Inventory-Questionnaire were less common in cognitively asymptomatic mutation carriers than in non-carriers (5% versus 17%, P = 0.014) and the odds of experiencing at least one behavioural sign in cognitively asymptomatic mutation carriers was lower than in non-carriers (odds ratio = 0.50, 95% confidence interval: 0.26-0.98, P = 0.042). Depression (56% versus 17%, P = 0.0003), apathy (40% versus 4%, P < 0.0001), disinhibition (16% versus 2%, P = 0.009), irritability (48% versus 9%, P = 0.0001), sleep changes (28% versus 7%, P = 0.003), and agitation (24% versus 6%, P = 0.008) were more common and the degree of self-rated depression more severe (mean Geriatric Depression Scale score of 2.8 versus 1.4, P = 0.006) in mildly symptomatic mutation carriers relative to non-carriers. Anxiety, appetite changes, delusions, and repetitive motor activity were additionally more common in overtly impaired mutation carriers. Similar to studies of late-onset Alzheimer's disease, we demonstrated increased rates of depression, apathy, and other behavioural symptoms in the mildly symptomatic, prodromal phase of autosomal dominant Alzheimer's disease that increased with disease severity. We did not identify any increased psychopathology in mutation carriers over non-carriers during the presymptomatic stage, suggesting these symptoms result when a threshold of neurodegeneration is reached rather than as life-long qualities. Unexpectedly, we found lower rates of depressive symptoms in cognitively asymptomatic mutation carriers.Item Genetic and clinical correlates of two neuroanatomical AI dimensions in the Alzheimer's disease continuum(Springer Nature, 2024-10-05) Wen, Junhao; Yang, Zhijian; Nasrallah, Ilya M.; Cui, Yuhan; Erus, Guray; Srinivasan, Dhivya; Abdulkadir, Ahmed; Mamourian, Elizabeth; Hwang, Gyujoon; Singh, Ashish; Bergman, Mark; Bao, Jingxuan; Varol, Erdem; Zhou, Zhen; Boquet-Pujadas, Aleix; Chen, Jiong; Toga, Arthur W.; Saykin, Andrew J.; Hohman, Timothy J.; Thompson, Paul M.; Villeneuve, Sylvia; Gollub, Randy; Sotiras, Aristeidis; Wittfeld, Katharina; Grabe, Hans J.; Tosun, Duygu; Bilgel, Murat; An, Yang; Marcus, Daniel S.; LaMontagne, Pamela; Benzinger, Tammie L.; Heckbert, Susan R.; Austin, Thomas R.; Launer, Lenore J.; Espeland, Mark; Masters, Colin L.; Maruff, Paul; Fripp, Jurgen; Johnson, Sterling C.; Morris, John C.; Albert, Marilyn S.; Bryan, R. Nick; Resnick, Susan M.; Ferrucci, Luigi; Fan, Yong; Habes, Mohamad; Wolk, David; Shen, Li; Shou, Haochang; Davatzikos, Christos; Radiology and Imaging Sciences, School of MedicineAlzheimer's disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the "diffuse-AD" (R1) dimension shows widespread brain atrophy, and the "MTL-AD" (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE ε4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained model in the general population and two cognitively unimpaired cohorts of asymptomatic participants. In the general population, genome-wide association studies found 77 genes unrelated to APOE differentially associated with R1 and R2. Functional analyses revealed that these genes were overrepresented in differentially expressed gene sets in organs beyond the brain (R1 and R2), including the heart (R1) and the pituitary gland, muscle, and kidney (R2). These genes were enriched in biological pathways implicated in dendritic cells (R2), macrophage functions (R1), and cancer (R1 and R2). Several of them were "druggable genes" for cancer (R1), inflammation (R1), cardiovascular diseases (R1), and diseases of the nervous system (R2). The longitudinal progression showed that APOE ε4, amyloid, and tau were associated with R2 at early asymptomatic stages, but this longitudinal association occurs only at late symptomatic stages in R1. Our findings deepen our understanding of the multifaceted pathogenesis of AD beyond the brain. In early asymptomatic stages, the two dimensions are associated with diverse pathological mechanisms, including cardiovascular diseases, inflammation, and hormonal dysfunction-driven by genes different from APOE-which may collectively contribute to the early pathogenesis of AD. All results are publicly available at https://labs-laboratory.com/medicine/ .Item Genomic loci influence patterns of structural covariance in the human brain(National Academy of Science, 2023) Wen, Junhao; Nasrallah, Ilya M.; Abdulkadir, Ahmed; Satterthwaite, Theodore D.; Yang, Zhijian; Erus, Guray; Robert-Fitzgerald, Timothy; Singh, Ashish; Sotiras, Aristeidis; Boquet-Pujadas, Aleix; Mamourian, Elizabeth; Doshi, Jimit; Cui, Yuhan; Srinivasan, Dhivya; Skampardoni, Ioanna; Chen, Jiong; Hwang, Gyujoon; Bergman, Mark; Bao, Jingxuan; Veturi, Yogasudha; Zhou, Zhen; Yang, Shu; Dazzan, Paola; Kahn, Rene S.; Schnack, Hugo G.; Zanetti, Marcus V.; Meisenzahl, Eva; Busatto, Geraldo F.; Crespo-Facorro, Benedicto; Pantelis, Christos; Wood, Stephen J.; Zhuo, Chuanjun; Shinohara, Russell T.; Gur, Ruben C.; Gur, Raquel E.; Koutsouleris, Nikolaos; Wolf, Daniel H.; Saykin, Andrew J.; Ritchie, Marylyn D.; Shen, Li; Thompson, Paul M.; Colliot, Olivier; Wittfeld, Katharina; Grabe, Hans J.; Tosun, Duygu; Bilgel, Murat; An, Yang; Marcus, Daniel S.; LaMontagne, Pamela; Heckbert, Susan R.; Austin, Thomas R.; Launer, Lenore J.; Espeland, Mark; Masters, Colin L.; Maruff, Paul; Fripp, Jurgen; Johnson, Sterling C.; Morris, John C.; Albert, Marilyn S.; Bryan, R. Nick; Resnick, Susan M.; Fan, Yong; Habes, Mohamad; Wolk, David; Shou, Haochang; Davatzikos, Christos; Radiology and Imaging Sciences, School of MedicineNormal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.Item Partial Volume Correction in Quantitative Amyloid Imaging.(Elsevier, 2015-02-15) Su, Yi; Blazey, Tyler M.; Snyder, Abraham Z.; Raichle, Marcus E.; Marcus, Daniel S.; Ances, Beau M.; Bateman, Randall J.; Cairns, Nigel J.; Aldea, Patricia; Cash, Lisa; Christensen, Jon J.; Friedrichsen, Karl; Hornbeck, Russ C.; Farrar, Angela M.; Owen, Christopher J.; Mayeux, Richard; Brickman, Adam M.; Klunk, William; Price, Julie C.; Thompson, Paul M.; Ghetti, Bernardino; Saykin, Andrew J.; Sperling, Reisa A.; Johnson, Keith A.; Schofield, Peter R.; Buckles, Virginia; Morris, John C.; Benzinger, Tammie LS; Department of Pathology & Laboratory Medicine, IU School of MedicineAmyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition.Item Preferential degradation of cognitive networks differentiates Alzheimer's disease from ageing(Oxford University Press, 2018-05-01) Chhatwal, Jasmeer P.; Schultz, Aaron P.; Johnson, Keith A.; Hedden, Trey; Jaimes, Sehily; Benzinger, Tammie L S.; Jack, Clifford; Ances, Beau M.; Ringman, John M.; Marcus, Daniel S.; Ghetti, Bernardino; Farlow, Martin R.; Danek, Adrian; Levin, Johannes; Yakushev, Igor; Laske, Christoph; Koeppe, Robert A.; Galasko, Douglas R.; Xiong, Chengjie; Masters, Colin L.; Schofield, Peter R.; Kinnunen, Kirsi M.; Salloway, Stephen; Martins, Ralph N.; McDade, Eric; Cairns, Nigel J.; Buckles, Virginia D.; Morris, John C.; Bateman, Randall; Sperling, Reisa A.; Pathology and Laboratory Medicine, School of MedicineConverging evidence from structural, metabolic and functional connectivity MRI suggests that neurodegenerative diseases, such as Alzheimer's disease, target specific neural networks. However, age-related network changes commonly co-occur with neuropathological cascades, limiting efforts to disentangle disease-specific alterations in network function from those associated with normal ageing. Here we elucidate the differential effects of ageing and Alzheimer's disease pathology through simultaneous analyses of two functional connectivity MRI datasets: (i) young participants harbouring highly-penetrant mutations leading to autosomal-dominant Alzheimer's disease from the Dominantly Inherited Alzheimer's Network (DIAN), an Alzheimer's disease cohort in which age-related comorbidities are minimal and likelihood of progression along an Alzheimer's disease trajectory is extremely high; and (ii) young and elderly participants from the Harvard Aging Brain Study, a cohort in which imaging biomarkers of amyloid burden and neurodegeneration can be used to disambiguate ageing alone from preclinical Alzheimer's disease. Consonant with prior reports, we observed the preferential degradation of cognitive (especially the default and dorsal attention networks) over motor and sensory networks in early autosomal-dominant Alzheimer's disease, and found that this distinctive degradation pattern was magnified in more advanced stages of disease. Importantly, a nascent form of the pattern observed across the autosomal-dominant Alzheimer's disease spectrum was also detectable in clinically normal elderly with clear biomarker evidence of Alzheimer's disease pathology (preclinical Alzheimer's disease). At the more granular level of individual connections between node pairs, we observed that connections within cognitive networks were preferentially targeted in Alzheimer's disease (with between network connections relatively spared), and that connections between positively coupled nodes (correlations) were preferentially degraded as compared to connections between negatively coupled nodes (anti-correlations). In contrast, ageing in the absence of Alzheimer's disease biomarkers was characterized by a far less network-specific degradation across cognitive and sensory networks, of between- and within-network connections, and of connections between positively and negatively coupled nodes. We go on to demonstrate that formalizing the differential patterns of network degradation in ageing and Alzheimer's disease may have the practical benefit of yielding connectivity measurements that highlight early Alzheimer's disease-related connectivity changes over those due to age-related processes. Together, the contrasting patterns of connectivity in Alzheimer's disease and ageing add to prior work arguing against Alzheimer's disease as a form of accelerated ageing, and suggest multi-network composite functional connectivity MRI metrics may be useful in the detection of early Alzheimer's disease-specific alterations co-occurring with age-related connectivity changes. More broadly, our findings are consistent with a specific pattern of network degradation associated with the spreading of Alzheimer's disease pathology within targeted neural networks.Item Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study(Elsevier, 2018-01) Kinnunen, Kirsi M.; Cash, David M.; Poole, Teresa; Frost, Chris; Benzinger, Tammie L. S.; Ahsan, R. Laila; Leung, Kelvin K.; Cardoso, M. Jorge; Modat, Marc; Malone, Ian B.; Morris, John C.; Bateman, Randall J.; Marcus, Daniel S.; Goate, Alison; Salloway, Stephen P.; Correia, Stephen; Sperling, Reisa A.; Chhatwal, Jasmeer P.; Mayeux, Richard P.; Brickman, Adam M.; Martins, Ralph N.; Farlow, Martin R.; Ghetti, Bernardino; Saykin, Andrew J.; Jack, Clifford R.; Schofield, Peter R.; McDade, Eric; Weiner, Michael W.; Ringman, John M.; Thompson, Paul M.; Masters, Colin L.; Rowe, Christopher C.; Rossor, Martin N.; Ourselin, Sebastien; Fox, Nick C.; Neurology, School of MedicineINTRODUCTION: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. METHODS: Serial T1-weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. RESULTS: Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. DISCUSSION: Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression.Item Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease(Mary Ann Liebert, 2021) Smith, Robert X.; Strain, Jeremy F.; Tanenbaum, Aaron; Fagan, Anne M.; Hassenstab, Jason; McDade, Eric; Schindler, Suzanne E.; Gordon, Brian A.; Xiong, Chengjie; Chhatwal, Jasmeer; Jack, Clifford, Jr.; Karch, Celeste; Berman, Sarah; Brosch, Jared R.; Lah, James J.; Brickman, Adam M.; Cash, David M.; Fox, Nick C.; Graff-Radford, Neill R.; Levin, Johannes; Noble, James; Holtzman, David M.; Masters, Colin L.; Farlow, Martin R.; Laske, Christoph; Schofield, Peter R.; Marcus, Daniel S.; Morris, John C.; Benzinger, Tammie L. S.; Bateman, Randall J.; Ances, Beau M.; Neurology, School of MedicineAim: Identify a global resting-state functional connectivity (gFC) signature in mutation carriers (MC) from the Dominantly Inherited Alzheimer Network (DIAN). Assess the gFC with regard to amyloid (A), tau (T), and neurodegeneration (N) biomarkers, and estimated years to symptom onset (EYO). Introduction: Cross-sectional measures were assessed in MC (n = 171) and mutation noncarrier (NC) (n = 70) participants. A functional connectivity (FC) matrix that encompassed multiple resting-state networks was computed for each participant. Methods: A global FC was compiled as a single index indicating FC strength. The gFC signature was modeled as a nonlinear function of EYO. The gFC was linearly associated with other biomarkers used for assessing the AT(N) framework, including cerebrospinal fluid (CSF), positron emission tomography (PET) molecular biomarkers, and structural magnetic resonance imaging. Results: The gFC was reduced in MC compared with NC participants. When MC participants were differentiated by clinical dementia rating (CDR), the gFC was significantly decreased in MC CDR >0 (demented) compared with either MC CDR 0 (cognitively normal) or NC participants. The gFC varied nonlinearly with EYO and initially decreased at EYO = −24 years, followed by a stable period followed by a further decline near EYO = 0 years. Irrespective of EYO, a lower gFC associated with values of amyloid PET, CSF Aβ1–42, CSF p-tau, CSF t-tau, 18F-fluorodeoxyglucose, and hippocampal volume. Conclusions: The gFC correlated with biomarkers used for defining the AT(N) framework. A biphasic change in the gFC suggested early changes associated with CSF amyloid and later changes associated with hippocampal volume.Item Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease(Elsevier, 2018-09-27) Joseph-Mathurin, Nelly; Su, Yi; Blazey, Tyler M.; Jasielec, Mateusz; Vlassenko, Andrei; Friedrichsen, Karl; Gordon, Brian A.; Hornbeck, Russ C.; Cash, Lisa; Ances, Beau M.; Veale, Thomas; Cash, David M.; Brickman, Adam M.; Buckles, Virginia; Cairns, Nigel J.; Cruchaga, Carlos; Goate, Alison; Jack, Clifford R., Jr.; Karch, Celeste; Klunk, William; Koeppe, Robert A.; Marcus, Daniel S.; Mayeux, Richard; McDade, Eric; Noble, James M.; Ringman, John; Saykin, Andrew J.; Thompson, Paul M.; Xiong, Chengjie; Morris, John C.; Bateman, Randall J.; Benzinger, Tammie L. S.; Dominantly Inherited Alzheimer Network; Radiology and Imaging Sciences, School of MedicineIntroduction: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure.