Increased white matter MRI T1 hypointensity volume in young- onset Alzheimer- s disease patients is not accounted for by age or cardiovascular risk factors
Flaherty, Ryn; Ezzo, Rania; Collins, Jessica A.; Krivensky, Samantha; Eckbo, Ryan; Vemuri, Prashanthi; Borowski, Bret J.; Iaccarino, Leonardo; La Joie, Renaud; Lesman‐segev, Orit H.; Bourakova, Viktoriya; Eloyan, Ani; Aisen, Paul S.; Fagan, Anne; Foroud, Tatiana M.; Gatsonis, Constantine; Jack, Clifford R.; Kramer, Joel H.; Koeppe, Robert A.; Saykin, Andrew J.; Toga, Arthur W.; Day, Gregory S; Graff‐radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Onyike, Chiadi U.; Rogalski, Emily J.; Salloway, Stephen P.; Wolk, David A.; Wingo, Thomas S.; Carrillo, Maria C.; Apostolova, Liana G.; Rabinovici, Gil D.; Dickerson, Brad C.
2020-12
Citation
Flaherty, Ryn; Ezzo, Rania; Collins, Jessica A.; Krivensky, Samantha; Eckbo, Ryan; Vemuri, Prashanthi; Borowski, Bret J.; Iaccarino, Leonardo; La Joie, Renaud; Lesman‐segev, Orit H. ; Bourakova, Viktoriya; Eloyan, Ani; Aisen, Paul S.; Fagan, Anne; Foroud, Tatiana M.; Gatsonis, Constantine; Jack, Clifford R.; Kramer, Joel H.; Koeppe, Robert A.; Saykin, Andrew J.; Toga, Arthur W.; Day, Gregory S; Graff‐radford, Neill R. ; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Onyike, Chiadi U.; Rogalski, Emily J.; Salloway, Stephen P.; Wolk, David A.; Wingo, Thomas S.; Carrillo, Maria C.; Apostolova, Liana G.; Rabinovici, Gil D.; Dickerson, Brad C. (2020). "Increased white matter MRI T1 hypointensity volume in young- onset Alzheimer- s disease patients is not accounted for by age or cardiovascular risk factors." Alzheimer’s & Dementia 16: n/a-n/a.
Abstract
BackgroundWhite matter (WM) hypointensity volume in T1 MRI correlates strongly with T2 hyperintensities and both are typically associated with advancing age and vascular brain injury (VBI). Recent research has suggested that Alzheimer- s Disease (AD) neuropathologic changes (ADNC) also increases WM hypointensity volume. Sporadic early onset AD (EOAD) patients provide a unique model to examine the relationship between ADNC biomarkers and WM hypointensity volume in the absence of advanced age, cardiovascular injury, or autosomal dominant genetic mutations.MethodIncluded in the analysis were sporadic EOAD patients (n = 75) and cognitively normal controls (n = 39) from the Longitudinal Alzheimer- s Disease Study (LEADS) for whom full demographic and health information were available. WM hypointensity volume in T1 MRI was segmented by Freesurfer and corrected for total white matter volume. Multiple- factor ANOVA models with logarithmic transformations were used to determine the effects of age, cohort, and presence of cardiovascular conditions on WM hypointensity volume. Further multiple- factor ANOVA models assessed whether the addition of covariates improved the model fit.ResultIn a reproduction of prior research, WM hypointensity volume was correlated with age for controls (p < 0.05), but not for EOAD patients. We additionally found an effect of cohort, such that EOAD patients had a higher mean WM hypointensity volume than controls when accounting for age (p < 0.05). No difference in the presence or number of cardiovascular conditions was found between groups. Additionally, no correlation was found between WM hypointensity volume and the presence or number of cardiovascular conditions. Including cardiovascular condition as a covariate failed to improve the model fit, even when accounting for interaction effects.ConclusionThese results support the hypothesis that patients with ADNC have higher WM hypointensity volume beyond what would be expected based on aging or cardiovascular risk factors. Further research is needed to assess the co- localization of WM hypointensities with cortical degradation, amyloid pathology, and tau pathology.Publisher
Wiley Periodicals, Inc.
ISSN
1552-5260 1552-5279
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