TY - JOUR
T1 - Divergent magnetic resonance imaging atrophy patterns in Alzheimer's disease and primary age-related tauopathy
AU - Quintas-Neves, Miguel
AU - Teylan, Merilee A.
AU - Morais-Ribeiro, Rafaela
AU - Almeida, Francisco
AU - Mock, Charles N.
AU - Kukull, Walter A.
AU - Crary, John F.
AU - Oliveira, Tiago Gil
N1 - Funding Information:
The NACC database is funded by NIA / NIH Grant U01 AG016976 and U24 AG072122 . NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD); R01 AG054008, R01 NS095252, R01 AG060961, R01 NS086736, and the Tau Consortium (PI John F. Crary MD, PhD). This work was funded by the Portuguese Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020.
Funding Information:
The NACC database is funded by NIA/NIH Grant U01 AG016976 and U24 AG072122. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD); R01 AG054008, R01 NS095252, R01 AG060961, R01 NS086736, and the Tau Consortium (PI John F. Crary MD, PhD). This work was funded by the Portuguese Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020.
Publisher Copyright:
© 2022
PY - 2022/9
Y1 - 2022/9
N2 - Our study compared brain MRI with neuropathological findings in patients with primary age-related tauopathy (PART) and Alzheimer's disease (AD), while assessing the relationship between brain atrophy and clinical impairment. We analyzed 233 participants: 32 with no plaques (“definite” PART—BRAAK stage higher than 0 and CERAD 0), and 201 cases within the AD spectrum, with 25 with sparse (CERAD 1), 76 with moderate (CERAD 2), and 100 with severe (CERAD 3) degrees of neuritic plaques. Upon correcting for age, sex, and age difference at MRI and death, there were significantly higher levels of atrophy in CERAD 3 compared to CERAD 1–2 and a trend compared to PART (p = 0.06). In the anterior temporal region, there was a trend for higher levels of atrophy in PART compared to Alzheimer's disease spectrum cases with CERAD 1 (p = 0.08). We then assessed the correlation between regional brain atrophy and CDR sum of boxes score for PART and AD, and found that overall cognition deficits are directly correlated with regional atrophy in the AD continuum, but not in definite PART. We further observed correlations between regional brain atrophy with multiple neuropsychological metrics in AD, with PART showing specific correlations between language deficits and anterior temporal atrophy. Overall, these findings support PART as an independent pathologic process from AD.
AB - Our study compared brain MRI with neuropathological findings in patients with primary age-related tauopathy (PART) and Alzheimer's disease (AD), while assessing the relationship between brain atrophy and clinical impairment. We analyzed 233 participants: 32 with no plaques (“definite” PART—BRAAK stage higher than 0 and CERAD 0), and 201 cases within the AD spectrum, with 25 with sparse (CERAD 1), 76 with moderate (CERAD 2), and 100 with severe (CERAD 3) degrees of neuritic plaques. Upon correcting for age, sex, and age difference at MRI and death, there were significantly higher levels of atrophy in CERAD 3 compared to CERAD 1–2 and a trend compared to PART (p = 0.06). In the anterior temporal region, there was a trend for higher levels of atrophy in PART compared to Alzheimer's disease spectrum cases with CERAD 1 (p = 0.08). We then assessed the correlation between regional brain atrophy and CDR sum of boxes score for PART and AD, and found that overall cognition deficits are directly correlated with regional atrophy in the AD continuum, but not in definite PART. We further observed correlations between regional brain atrophy with multiple neuropsychological metrics in AD, with PART showing specific correlations between language deficits and anterior temporal atrophy. Overall, these findings support PART as an independent pathologic process from AD.
KW - Alzheimer's disease
KW - Brain imaging
KW - MRI
KW - Primary age-related tauopathy
UR - http://www.scopus.com/inward/record.url?scp=85130874524&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2022.04.013
DO - 10.1016/j.neurobiolaging.2022.04.013
M3 - Article
AN - SCOPUS:85130874524
SN - 0197-4580
VL - 117
SP - 1
EP - 11
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -