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Age at onset reveals different functional connectivity abnormalities in prodromal Alzheimer’s disease

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Abstract

Age at symptom onset (AAO) underlies different Alzheimer’s disease (AD) clinical variants: late-onset AD (LOAD) is characterized by memory deficits, while early-onset AD (EOAD) presents predominantly with non-memory symptoms. The involvement of different neural networks may explain these distinct clinical phenotypes. In this study, we tested the hypothesis of an early and selective involvement of neural networks based on AAO in AD. Twenty memory clinic patients with prodromal AD (i.e., mild cognitive impairment with an AD-like cerebrospinal fluid profile) and 30 healthy controls underwent a cognitive evaluation and a resting state functional MRI exam. Independent component analysis was performed to assess functional connectivity (FC) in the following networks: default mode, frontoparietal, limbic, visual, and sensorimotor. Patients were stratified into late-onset (pLOAD) and early-onset (pEOAD) prodromal AD according to the AAO and controls were stratified into younger and older groups accordingly. Decreased FC within the default mode and the limbic networks was observed in pLOAD, while pEOAD showed lower FC in the frontoparietal and visual networks. The sensorimotor network did not show differences between groups. A significant association was found between memory and limbic network FC in pLOAD, and between executive functions and frontoparietal network FC in pEOAD, although the latter association did not survive multiple comparison correction. Our findings indicate that aberrant connectivity in memory networks is associated with pLOAD, while networks underlying executive and visuo-spatial functions are affected in pEOAD. These findings are in line with the hypothesis that the pathophysiological mechanisms underlying EOAD and LOAD are distinct.

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References

  • Adriaanse, S. M., Binnewijzend, M. A., Ossenkoppele, R., Tijms, B. M., van der Flier, W. M., Koene, T., Smits, L. L., Wink, A. M., Scheltens, P., van Berckel, B. N., & Barkhof, F. (2014). Widespread disruption of functional brain organization in early-onset Alzheimer’s disease. PLoS One, 9, e102995.

    PubMed  PubMed Central  Google Scholar 

  • Agosta, F., Pievani, M., Geroldi, C., Copetti, M., Frisoni, G. B., & Filippi, M. (2012). Resting state fMRI in Alzheimer’s disease: Beyond the default mode network. Neurobiology of Aging, 33, 1564–1578.

    PubMed  Google Scholar 

  • Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., Snyder, P. J., Carrillo, M. C., Thies, B., & Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7, 270–279.

    Google Scholar 

  • Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. Neuroimage, 38, 95–113.

    PubMed  Google Scholar 

  • Bell, A. J., & Sejnowski, T. (1995). An information-maximization approach to blind separation and blind deconvolution. Neural Computation, 7, 1129–1159.

    CAS  PubMed  Google Scholar 

  • Brier, M. R., Thomas, J. B., Snyder, A. Z., Benzinger, T. L., Zhang, D., Raichle, M. E., Holtzman, D. M., Morris, J. C., & Ances, B. M. (2012). Loss of intra- and inter-network resting state functional connections with Alzheimer’s disease progression. The Journal of Neuroscience, 32, 8890–8899.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., & Mintun, M. A. (2005). Molecular, structural, and functional characterization of Alzheimer's disease: Evidence for a relationship between default activity, amyloid, and memory. The Journal of Neuroscience, 25, 7709–7717.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Calhoun, V. D., Adali, T., Pearlson, G. D., & Pekar, J. J. (2011). A method for making group inferences from functional MRI data using independent component analysis. Human Brain Mapping, 14, 140–151.

    Google Scholar 

  • Cavedo, E., Pievani, M., Boccardi, M., Galluzzi, S., Bocchetta, M., Bonetti, M., Thompson, P. M., & Frisoni, G. B. (2014). Medial temporal atrophy in early and late-onset Alzheimer’s disease. Neurobiology of Aging, 35, 2004–2012.

    PubMed  PubMed Central  Google Scholar 

  • Cho, H., Choi, J. Y., Lee, S. H., Lee, J. H., Choi, Y. C., Ryu, Y. H., Lee, M. S., & Lyoo, C. H. (2017). Excessive tau accumulation in the parieto-occipital cortex characterizes early onset Alzheimer’s disease. Neurobiology of Aging, 53, 103–111.

    CAS  PubMed  Google Scholar 

  • Cho, H., Seo, S. W., Kim, J. H., Suh, M. K., Lee, J. H., Choe, Y. S., Lee, K. H., Kim, J. S., Kim, G. H., Noh, Y., Ye, B. S., Kim, H. J., Yoon, C. W., Chin, J., & Na, D. L. (2013). Amyloid deposition in early onset versus late onset Alzheimer’s disease. Journal of Alzheimer's Disease, 35, 813–821.

    PubMed  Google Scholar 

  • Dillen, K. N. H., Jacobs, H. I. L., Kukolja, J., von Reutern, B., Richter, N., Onur, Ö. A., Dronse, J., Langen, K. J., & Fink, G. R. (2016). Aberrant functional connectivity differentiates retrosplenial cortex from posterior cingulate cortex in prodromal Alzheimer’s disease. Neurobiology of Aging, 44, 114–126.

    PubMed  Google Scholar 

  • Ferri, C. P., Prince, M., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K., Hasegawa, K., Hendrie, H., Huang, Y., Jorm, A., Mathers, C., Menezes, P. R., Rimmer, E., Scazufca, M., & Alzheimer’s Disease International. (2005). Global prevalence of dementia: A Delphi consensus study. Lancet, 366, 2112–2117.

    PubMed  PubMed Central  Google Scholar 

  • Frisoni, G. B., Beltramello, A., Weiss, C., Geroldi, C., Bianchetti, A., & Trabucchi, M. (1996). Linear measures of atrophy in mild Alzheimer disease. American Journal of Neuroradiology, 17, 913–923.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frisoni, G. B., Pievani, M., Testa, C., Sabattoli, F., Bresciani, L., Bonetti, M., Beltramello, A., Hayashi, K. M., Toga, A. W., & Thompson, P. M. (2007). The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain, 130, 720–730.

    PubMed  Google Scholar 

  • Frisoni, G. B., Prestia, A., Zanetti, O., Galluzzi, S., Romano, M., Cotelli, M., Gennarelli, M., Binetti, G., Bocchio, L., Paghera, B., Amicucci, G., Bonetti, M., Benussi, L., Ghidoni, R., & Geroldi, C. (2009). Markers of Alzheimer’s disease in a population attending a memory clinic. Alzheimers Dement, 5, 307–317.

    PubMed  Google Scholar 

  • Gour, N., Felician, O., Didic, M., Koric, L., Gueriot, C., Chanoine, V., Confort-Gouny, S., Guye, M., Ceccaldi, M., & Ranjeva, J. P. (2014). Functional connectivity changes differ in early and late-onset Alzheimer’s disease. Human Brain Mapping, 35, 2978–2994.

    PubMed  Google Scholar 

  • Griffanti, L., Douaud, G., Bijsterbosch, J., Evangelisti, S., Alfaro-Almagro, F., Glasser, M. F., Duff, E. P., Fitzgibbon, S., Westphal, R., Carone, D., Beckmann, C. F., & Smith, S. M. (2017). Hand classification of fMRI ICA noise components. Neuroimage, 154, 188–205.

    PubMed  Google Scholar 

  • Grothe, M. J., & Teipel, S. J. (2016). Spatial patterns of atrophy, hypometabolism, and amyloid deposition in Alzheimer's disease correspond to dissociable functional brain networks. Human Brain Mapping, 37, 35–53.

    PubMed  Google Scholar 

  • Hafkemeijer, A., Altmann-Schneider, I., Oleksik, A. M., van de Wiel, L., Middelkoop, H. A., van Buchem, M. A., van der Grond, J., & Rombouts, S. A. (2013). Increased functionalconnectivity and brain atrophy in elderly with subjective memory complaints. Brain Connectivity, 3, 353–362.

    PubMed  PubMed Central  Google Scholar 

  • Jacobs, H. I., Radua, J., Lückmann, H. C., & Sack, A. T. (2013). Meta-analysis of functional network alterations in Alzheimer's disease: Toward a network biomarker. Neuroscience and Biobehavioral Reviews, 37, 753–765.

    PubMed  Google Scholar 

  • Kahn, I., Andrews-Hanna, J. R., Vincent, J. L., Snyder, A. Z., & Buckner, R. L. (2008). Distinct cortical anatomy linked to subregions of the medial temporal lobe revealed by intrinsic functional connectivity. Journal of Neurophysiology, 100, 129–139.

    PubMed  PubMed Central  Google Scholar 

  • Kalpouzos, G., Eustache, F., de la Sayette, V., Viader, F., Chételat, G., & Desgranges, B. (2005). Working memory and FDG-PET dissociate early and late onset Alzheimer disease patients. Journal of Neurology, 252, 548–558.

    CAS  PubMed  Google Scholar 

  • Kas, A., De Souza, L. C., Samri, D., Bartolomeo, P., Lacomblez, L., Kalafat, M., Migliaccio, R., Thiebaut De Schotten, M., Cohen, L., Dubois, B., Habert, M. O., & Sarazin, M. (2011). Neural correlates of cognitive impairment in posterior cortical atrophy. Brain, 134, 1464–1478.

    PubMed  Google Scholar 

  • Laird, A. R., Fox, P. M., Eickhoff, S. B., Turner, J. A., Ray, K. L., McKay, D. R., Glahn, D. C., Beckmann, C. F., Smith, S. M., & Fox, P. T. (2011). Behavioral interpretations of intrinsic connectivity networks. Journal of Cognitive Neuroscience, 23, 4022–4037.

    PubMed  PubMed Central  Google Scholar 

  • Lehmann, M., Ghosh, P. M., Madison, C., Laforce Jr., R., Corbetta-Rastelli, C., Weiner, M. W., Greicius, M. D., Seeley, W. W., Gorno-Tempini, M. L., Rosen, H. J., Miller, B. L., Jagust, W. J., & Rabinovici, G. D. (2013). Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease. Brain, 136, 844–858.

    PubMed  PubMed Central  Google Scholar 

  • Lehmann, M., Madison, C., Ghosh, P. M., Miller, Z. A., Greicius, M. D., Kramer, J. H., Coppola, G., Miller, B. L., Jagust, W. J., Gorno-Tempini, M. L., Seeley, W. W., & Rabinovici, G. D. (2015). Loss of functional connectivity is greater outside the default mode network in non-familial early-onset Alzheimer’s disease variants. Neurobiology of Aging, 36, 2678–2686.

    PubMed  PubMed Central  Google Scholar 

  • Li, Y. O., Adali, T., & Calhoun, V. D. (2007). Estimating the number of independent components for functional magnetic resonance imaging data. Human Brain Mapping, 28, 1251–1266.

    PubMed  PubMed Central  Google Scholar 

  • Mattsson, N., Zetterberg, H., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S. K., van der Flier, W. M., Blankenstein, M. A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M., Tsolaki, M., Mulugeta, E., Rosén, E., Aarsland, D., Visser, P. J., Schröder, J., Marcusson, J., de Leon, M., Hampel, H., Scheltens, P., Pirttilä, T., Wallin, A., Jönhagen, M. E., Minthon, L., Winblad, B., & Blennow, K. (2009). CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA, 302, 385–393.

    CAS  PubMed  Google Scholar 

  • McDonald, C. R., McEvoy, L. K., Gharapetian, L., Fennema-Notestine, C., Hagler Jr., D. J., Holland, D., Koyama, A., Brewer, J. B., & Dale, A. M. (2009). Regional rates of neocortical atrophy fromnormal aging to early Alzheimer disease. Neurology, 73, 457–465.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Migliaccio, R., Gallea, C., Kas, A., Perlbarg, V., Samri, D., Trotta, L., Michon, A., Lacomblez, L., Dubois, B., Lehericy, S., & Bartolomeo, P. (2016). Functional connectivity of ventral and dorsal visual streams in posterior cortical atrophy. Journal of Alzheimer’s Disease, 51, 1119–1130.

    PubMed  Google Scholar 

  • Millington, R. S., James-Galton, M., Maia Da Silva, M. N., Plant, G. T., & Bridge, H. (2017). Lateralized occipital degeneration in posterior cortical atrophy predicts visual field deficits. Neuroimage Clinical, 14, 242–249.

    PubMed  PubMed Central  Google Scholar 

  • Möller, C., Vrenken, H., Jiskoot, L., Versteeg, A., Barkhof, F., Scheltens, P., & van der Flier, W. M. (2013). Different patterns of gray matter atrophy in early and late onset Alzheimer’s disease. Neurobiology of Aging, 34, 2014–2022.

    PubMed  Google Scholar 

  • Moretti, D. V., Pievani, M., Pini, L., Guerra, U. P., Paghera, B., & Frisoni, G. B. (2017). Cerebral PET glucose hypometabolism in subjects with mild cognitive impairment and higher EEG high-alpha/low-alpha frequency power ratio. Neurobiology of Aging, 58, 213–224.

    CAS  PubMed  Google Scholar 

  • Murray, M. E., Graff-Radford, N. R., Ross, O. A., Petersen, R. C., Duara, R., & Dickson, D. W. (2011). Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: A retrospective study. Lancet Neurology, 10, 785–796.

    PubMed  PubMed Central  Google Scholar 

  • Niendam, T. A., Laird, A. R., Ray, K. L., Dean, Y. M., Glahn, D. C., & Carter, C. S. (2013). Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cognitive, Affective, & Behavioral Neuroscience, 12, 241–268.

    Google Scholar 

  • Ossenkoppele, R., Cohn-Sheehy, B. I., La Joie, R., Vogel, J. W., Möller, C., Lehmann, M., van Berckel, B. N., Seeley, W. W., Pijnenburg, Y. A., Gorno-Tempini, M. L., Kramer, J. H., Barkhof, F., Rosen, H. J., van der Flier, W. M., Jagust, W. J., Miller, B. L., Scheltens, P., & Rabinovici, G. D. (2015). Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer’s disease. Human Brain Mapping, 36, 4421–4437.

    PubMed  PubMed Central  Google Scholar 

  • Ossenkoppele, R., Schonhaut, D. R., Schöll, M., Lockhart, S. N., Ayakta, N., Baker, S. L., O'Neil, J. P., Janabi, M., Lazaris, A., Cantwell, A., Vogel, J., Santos, M., Miller, Z. A., Bettcher, B. M., Vossel, K. A., Kramer, J. H., Gorno-Tempini, M. L., Miller, B. L., Jagust, W. J., & Rabinovici, G. D. (2016). Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease. Brain, 139, 1551–1567.

    PubMed  PubMed Central  Google Scholar 

  • Ossenkoppele, R., Zwan, M. D., Tolboom, N., van Assema, D. M., Adriaanse, S. F., Kloet, R. W., Boellaard, R., Windhorst, A. D., Barkhof, F., Lammertsma, A. A., Scheltens, P., van der Flier, W. M., & van Berckel, B. N. (2012). Amyloid burden and metabolic function in early-onset Alzheimer’s disease: parietal lobe involvement. Brain, 135, 2115–1125.

    PubMed  Google Scholar 

  • Palmqvist, S., Schöll, M., Strandberg, O., Mattsson, N., Stomrud, E., Zetterberg, H., Blennow, K., Landau, S., Jagust, W., & Hansson, O. (2017). Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nature Communications, 8, 1214.

    PubMed  PubMed Central  Google Scholar 

  • Pievani, M., Filippini, N., Van Den Heuvel, M. P., Cappa, S. F., & Frisoni, G. B. (2014). Brain connectivity in neurodegenerative diseases - from phenotype to proteinopathy. Nature Reviews. Neurology, 10, 620–633.

    PubMed  Google Scholar 

  • Pievani, M., Pini, L., Cappa, S. F., & Frisoni, G. B. (2016). Brain networks stimulation in dementia: Insights from functional imaging. Current Opinion in Neurology, 29, 756–762.

    PubMed  Google Scholar 

  • Pievani, M., Pini, L., Ferrari, C., Pizzini, F. B., Boscolo Galazzo, I., Cobelli, C., Cotelli, M., Manenti, R., & Frisoni, G. B. (2017). Coordinate-based meta-analysis of the default mode andsalience network for target identification in non-invasive brain stimulation of Alzheimer’s disease and behavioral variant frontotemporal dementia networks. Journal of Alzheimer's Disease, 57, 825–843.

    PubMed  Google Scholar 

  • Pini, L., Manenti, R., Cotelli, M., Pizzini, F. B., Frisoni, G. B., & Pievani, M. (2019). Non-invasive brain stimulation in dementia: A complex network story. Neurodegenerative Diseases, 18, 281–301.

    Google Scholar 

  • Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage, 59, 2142–2154.

    PubMed  Google Scholar 

  • Rabinovici, G. D., Furst, A. J., Alkalay, A., Racine, C. A., O'Neil, J. P., Janabi, M., Baker, S. L., Agarwal, N., Bonasera, S. J., Mormino, E. C., Weiner, M. W., Gorno-Tempini, M. L., Rosen, H. J., Miller, B. L., & Jagust, W. J. (2010). Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden. Brain, 133, 512–528.

    PubMed  PubMed Central  Google Scholar 

  • Ranganath, C., & Ritchey, M. (2012). Two cortical systems for memory-guided behaviour. Nature Reviews. Neuroscience, 13, 713–726.

    CAS  PubMed  Google Scholar 

  • Ritchey, M., Libby, L. A., & Ranganath, C. (2015). Cortico-hippocampal systems involved in memory and cognition: The PMAT framework. Progress in Brain Research, 219, 45–64.

    PubMed  Google Scholar 

  • Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., & Greicius, M. D. (2009). Neurodegenerative diseases target large-scale human brain networks. Neuron, 62, 42–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sestieri, C., Corbetta, M., Romani, G. L., & Shulman, G. L. (2011). Episodic memory retrieval, parietal cortex, and the default mode network: Functional and topographicanalyses. The Journal of Neuroscience, 31, 4407–4420.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smith, S. M., Fox, P. T., Miller, K. L., Glahn, D. C., Fox, P. M., Mackay, C. E., Filippini, N., Watkins, K. E., Toro, R., Laird, A. R., & Beckmann, C. F. (2009). Correspondence of the brain’s functional architecture duringactivation and rest. Proceedings of the National Academy of Sciences, 106, 13040–13045.

    CAS  Google Scholar 

  • Smits, L. L., Pijnenburg, Y. A., Koedam, E. L., van der Vlies, A. E., Reuling, I. E., Koene, T., Teunissen, C. E., Scheltens, P., & van der Flier, W. M. (2012). Early onset Alzheimer’s disease is associated with a distinct neuropsychological profile. Journal of Alzheimer's Disease, 30, 101–108.

    PubMed  Google Scholar 

  • Sorg, C., Riedl, V., Muhlau, M., Calhoun, V. D., Eichele, T., Laer, L., Drzezga, A., Förstl, H., Kurz, A., Zimmer, C., & Wohlschlager, A. M. (2007). Selective changes of resting-state networks inindividuals at risk for Alzheimer’ s disease. Proceedings of the National Academy of Sciences, 104, 18760–18765.

    CAS  Google Scholar 

  • van der Flier, W. M., Pijnenburg, Y. A., Fox, N. C., & Scheltens, P. (2011). Early onset versus late-onset Alzheimer’s disease: The case of the missing APOE ε4 allele. Lancet Neurology, 10, 280–288.

    PubMed  Google Scholar 

  • Warren, J. D., Rohrer, J. D., Schott, J. M., Fox, N. C., Hardy, J., & Rossor, M. N. (2013). Molecular nexopathies: A new paradigm of neurodegenerative disease. Trends in Neurosciences, 36, 561–569.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Warren, J. D., Fletcher, P. D., & Golden, H. L. (2012). The paradox of syndromic diversity in Alzheimer disease. Nature Reviews. Neurology, 8, 451–464.

    CAS  PubMed  Google Scholar 

  • Zhang, H. Y., Wang, S. J., Liu, B., Ma, Z. L., Yang, M., Zhang, Z. J., & Teng, G. J. (2010). Resting brain connectivity: Changes during the progress of Alzheimer disease. Radiology, 256, 598–606.

    PubMed  Google Scholar 

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Funding

This work was supported by the Italian Ministry of Health (Giovani Ricercatori grant GR2011-02349787 and Ricerca Corrente).

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Authors and Affiliations

  1. Laboratory Alzheimer’s Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, via Pilastroni 4, 25125, Brescia, Italy

    Lorenzo Pini, Samantha Galluzzi, Roberta Baruzzi, Melissa Romano, Giovanni B. Frisoni & Michela Pievani

  2. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    Lorenzo Pini

  3. Alzheimer’s Unit - Memory Clinic, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Cristina Geroldi, Monica Bertocchi, Eugenia Chitò, Stefania Orini & Orazio Zanetti

  4. Neuropsychology Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Maria Cotelli & Sandra Rosini

  5. Radiology, Department of Health Services, Santa Maria degli Angeli Hospital, Pordenone, Italy

    Silvia Magnaldi

  6. Department of Radiology, Fondazione Poliambulanza, Brescia, Italy

    Mauro Morassi & Milena Cobelli

  7. Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Cristian Bonvicini

  8. Department of Laboratory Diagnostic, Biotechnology Laboratory, ASST Spedali Civili Brescia, Brescia, Italy

    Silvana Archetti

  9. Memory Clinic and LANVIE Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland

    Giovanni B. Frisoni

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  1. Lorenzo Pini
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Supplementary Fig. 1

Reduced grey matter volume in prodromal early-onset Alzheimer’s disease (pEOAD) compared to younger subjective cognitive complainers (ySC) and in prodromal late-onset Alzheimer’s disease (pLOAD) compared to elderly subjective cognitive complainers (eSC). Red-yellow: decreased volume (p<0.025 FWE-corrected corresponding to a two-tailed p<0.05). L: left; R: right. (PNG 855 kb)

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Pini, L., Geroldi, C., Galluzzi, S. et al. Age at onset reveals different functional connectivity abnormalities in prodromal Alzheimer’s disease. Brain Imaging and Behavior 14, 2594–2605 (2020). https://doi.org/10.1007/s11682-019-00212-6

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