Browsing by Author "Zaitsev, Alexander"

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    Dissociable spatial topography of cortical atrophy in early‐onset and late‐onset Alzheimer's disease: A head‐to‐head comparison of the LEADS and ADNI cohorts
    (Wiley, 2025) Katsumi, Yuta; Touroutoglou, Alexandra; Brickhouse, Michael; Eloyan, Ani; Eckbo, Ryan; Zaitsev, Alexander; La Joie, Renaud; Lagarde, Julien; Schonhaut, Daniel; Thangarajah, Maryanne; Taurone, Alexander; Vemuri, Prashanthi; Jack, Clifford R., Jr.; Dage, Jeffrey L.; Nudelman, Kelly N. H.; Foroud, Tatiana; Hammers, Dustin B.; Ghetti, Bernardino; Murray, Melissa E.; Newell, Kathy L.; Polsinelli, Angelina J.; Aisen, Paul; Reman, Rema; Beckett, Laurel; Kramer, Joel H.; Atri, Alireza; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Grant, Ian M.; Honig, Lawrence S.; Johnson, Erik C. B.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Stephen; Sha, Sharon; Turner, R. Scott; Wingo, Thomas S.; Wolk, David A.; Womack, Kyle; Carrillo, Maria C.; Rabinovici, Gil D.; Apostolova, Liana G.; Dickerson, Bradford C.; LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative; Neurology, School of Medicine
    Introduction: Early-onset and late-onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head-to-head comparison of cortical atrophy in EOAD and LOAD, using two large and well-characterized cohorts (LEADS and ADNI). Methods: We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early-stage AD), along with cognitively unimpaired participants. Results: After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. Discussion: Our findings point to the clinical utility of MRI-based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights: Early-onset Alzheimer's disease (EOAD) and late-onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.
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    Effects of APOE genotype on cortical atrophy in early onset Alzheimer’s disease
    (Wiley, 2025-01-09) Chan, Diane; Brickhouse, Michael; Zaitsev, Alexander; Wong, Bonnie; Hammers, Dustin B.; Dage, Jeffrey L.; Foroud, Tatiana M.; Eloyan, Ani; Nudelman, Kelly N.; Nemes, Sára; Carrillo, Maria C.; Rabinovici, Gil D.; Apostolova, Liana G.; Dickerson, Bradford C.; Touroutoglou, Alexandra; LEADS Consortium; Medical and Molecular Genetics, School of Medicine
    Background: APOE‐ɛ4 is a major risk factor for Alzheimer’s disease (AD); its effects have been examined in late‐onset AD (LOAD) but less so in early‐onset AD (EOAD). In LOAD, APOE genotype has strong effects on episodic memory and medial temporal lobe (MTL) atrophy (Wolk & Dickerson, 2010). However, EOAD often presents with more cognitive impairments in executive function, language, and visuospatial abilities than memory. These differences reflect more prominent atrophy in posterior lateral temporal and inferior parietal cortex that mainly constitute the EOAD‐signature of atrophy. Based on the cognitive and neuroanatomical profile of EOAD, we hypothesized that EOAD ɛ4 carriers will have relatively more atrophy in MTL regions subserving episodic memory, whereas non carriers would express more atrophy in cortical regions of the EOAD‐signature involved in executive function, language, and visuospatial abilities including inferior parietal and posterior temporal regions. We also expected worse performance on episodic memory tests in ɛ4 carriers with EOAD. Methods: We examined the effects of APOE genotype on cortical atrophy and episodic memory of 144 ɛ4 carriers and 117 ɛ4 non‐carriers with EOAD from the Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS). Between‐group comparisons using independent T‐tests were made for morphometric measures of cortical atrophy in MTL and hippocampus localized in LOAD as well as in cortical regions within our newly developed EOAD‐Signature tool (Touroutoglou et al., 2023). ANCOVA with Bonferonni’s correction was used to evaluate for effects of age on significant differences between groups. Results: As predicted, ɛ4 carriers with EOAD had more atrophy in the MTL and bilateral hippocampi, whereas non‐carriers had more atrophy in regions of the EOAD‐signature including bilateral caudal temporal, parietal lobule, middle frontal gyrus, mid temporal, posterior cingulate cortex, precuneus, superior frontal gyrus, superior parietal lobule. Post hoc vertex wise cortical maps further confirmed the specificity of the results. In addition, ɛ4 carriers had worse performance on episodic memory testing (AVLT delayed recall). These results were not explained by a difference in age between the groups. Conclusions: These results are consistent with prior work (Nemes et al. 2023) and support the hypothesis that the ɛ4 genotype modulates distinct neuroanatomic phenotypes of AD in EOAD patients.
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    The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort
    (Wiley, 2023) Touroutoglou, Alexandra; Katsumi, Yuta; Brickhouse, Michael; Zaitsev, Alexander; Eckbo, Ryan; Aisen, Paul; Beckett, Laurel; Dage, Jeffrey L.; Eloyan, Ani; Foroud, Tatiana; Ghetti, Bernardino; Griffin, Percy; Hammers, Dustin; Jack, Clifford R., Jr.; Kramer, Joel H.; Iaccarino, Leonardo; La Joie, Renaud; Mundada, Nidhi S.; Koeppe, Robert; Kukull, Walter A.; Murray, Melissa E.; Nudelman, Kelly; Polsinelli, Angelina J.; Rumbaugh, Malia; Soleimani-Meigooni, David N.; Toga, Arthur; Vemuri, Prashanthi; Atri, Alireza; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Stephen; Sha, Sharon; Turner, R. Scott; Wingo, Thomas S.; Wolk, David A.; Womack, Kyle; Carrillo, Maria C.; Rabinovici, Gil D.; Apostolova, Liana G.; Dickerson, Bradford C.; LEADS Consortium; Neurology, School of Medicine
    Introduction: Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. Methods: We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. Results: The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. Discussion: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. Highlights: We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.