Michael Marnane1, Osama O Al-Jawadi2, Shervin Mortazavi2, Kathleen J Pogorzelec2, Bing Wei Wang2, Howard H Feldman2, Ging-Yuek R Hsiung2. 1. From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada. michael.marnane@vch.ca. 2. From the Clinic for Alzheimer Disease and Related Disorders, Djavad Mowafaghian Center for Brain Health (M.M., O.O.A.-J., S.M., K.J.P., B.W.W., H.H.F., G.-Y.R.H.), and Department of Medicine, Division of Neurology (M.M., H.H.F., G.-Y.R.H.), University of British Columbia, Vancouver, Canada.
Abstract
OBJECTIVE: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study. METHODS: The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET. RESULTS: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aβ (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements. CONCLUSIONS: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.
OBJECTIVE: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study. METHODS: The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET. RESULTS: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aβ (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements. CONCLUSIONS: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.
Authors: Clifford R Jack; Matt A Bernstein; Bret J Borowski; Jeffrey L Gunter; Nick C Fox; Paul M Thompson; Norbert Schuff; Gunnar Krueger; Ronald J Killiany; Charles S Decarli; Anders M Dale; Owen W Carmichael; Duygu Tosun; Michael W Weiner Journal: Alzheimers Dement Date: 2010-05 Impact factor: 21.566
Authors: Alida A Gouw; Alexandra Seewann; Wiesje M van der Flier; Frederik Barkhof; Annemieke M Rozemuller; Philip Scheltens; Jeroen J G Geurts Journal: J Neurol Neurosurg Psychiatry Date: 2010-10-09 Impact factor: 10.154
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Christopher M Clark; Paul S Aisen; Ronald C Petersen; Kaj Blennow; Holly Soares; Adam Simon; Piotr Lewczuk; Robert Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2009-04 Impact factor: 10.422
Authors: Thaddeus J Haight; Susan M Landau; Owen Carmichael; Christopher Schwarz; Charles DeCarli; William J Jagust Journal: JAMA Neurol Date: 2013-08 Impact factor: 18.302
Authors: Marije R Benedictus; Jeroen D C Goos; Maja A A Binnewijzend; Majon Muller; Frederik Barkhof; Philip Scheltens; Niels D Prins; Wiesje M van der Flier Journal: Neurobiol Aging Date: 2013-05-31 Impact factor: 4.673
Authors: Adam M Brickman; Frank A Provenzano; Jordan Muraskin; Jennifer J Manly; Sonja Blum; Zoltan Apa; Yaakov Stern; Truman R Brown; José A Luchsinger; Richard Mayeux Journal: Arch Neurol Date: 2012-12
Authors: Michael Ewers; Matthias Brendel; Angela Rizk-Jackson; Axel Rominger; Peter Bartenstein; Norbert Schuff; Michael W Weiner Journal: Neuroimage Clin Date: 2013-11-04 Impact factor: 4.881
Authors: Dustin B Hammers; Taylor J Atkinson; Bonnie C A Dalley; Kayla R Suhrie; Kevin P Horn; Kelli M Rasmussen; Britney E Beardmore; Lance D Burrell; Kevin Duff; John M Hoffman Journal: Am J Alzheimers Dis Other Demen Date: 2017-04-12 Impact factor: 2.035
Authors: Julia A Scott; Meredith N Braskie; Duygu Tosun; Pauline Maillard; Paul M Thompson; Michael Weiner; Charles DeCarli; Owen T Carmichael Journal: Neurobiol Aging Date: 2016-08-24 Impact factor: 4.673
Authors: Michael L Alosco; Michael A Sugarman; Lilah M Besser; Yorghos Tripodis; Brett Martin; Joseph N Palmisano; Neil W Kowall; Rhoda Au; Jesse Mez; Charles DeCarli; Thor D Stein; Ann C McKee; Ronald J Killiany; Robert A Stern Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Sara E Berman; Lindsay R Clark; Leonardo A Rivera-Rivera; Derek Norton; Annie M Racine; Howard A Rowley; Barbara B Bendlin; Kaj Blennow; Henrik Zetterberg; Cynthia M Carlsson; Sanjay Asthana; Patrick Turski; Oliver Wieben; Sterling C Johnson Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Katie E Osborn; Dandan Liu; Lauren R Samuels; Elizabeth E Moore; Francis E Cambronero; Lealani Mae Y Acosta; Susan P Bell; Michelle A Babicz; Elizabeth A Gordon; Kimberly R Pechman; L Taylor Davis; Katherine A Gifford; Timothy J Hohman; Kaj Blennow; Henrik Zetterberg; Angela L Jefferson Journal: Neurobiol Aging Date: 2018-04-03 Impact factor: 4.673
Authors: David A Bennett; Aron S Buchman; Patricia A Boyle; Lisa L Barnes; Robert S Wilson; Julie A Schneider Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472