TY - JOUR
T1 - The cross-sectional association between amyloid burden and white matter hyperintensities in older adults without cognitive impairment
T2 - A systematic review and meta-analysis
AU - Twait, Emma L.
AU - Min, Britt
AU - Beran, Magdalena
AU - Vonk, Jet M. J.
AU - Geerlings, Mirjam I.
N1 - Funding Information: This study was conducted in the context of the Netherlands Consortium of Dementia Cohorts (NCDC); NCDC receives funding in the context of Deltaplan Dementie from ZonMw (project number 73305095005 ) and Alzheimer Nederland. J.M.J. Vonk was supported by an Alzheimer Nederland Fellowship ( WE.15-2018-05 ), ZonMw Veni grant (project number 09150161810017 ), and NIH K99/R00 Pathway to Independence award (NIA K99AG066934 ). We thank Paulien Wiersma, Librarian Medical Sciences at University Utrecht, for her help in preparing the systematic search strategy. Funding Information: This study was conducted in the context of the Netherlands Consortium of Dementia Cohorts (NCDC); NCDC receives funding in the context of Deltaplan Dementie from ZonMw (project number 73305095005) and Alzheimer Nederland. J.M.J. Vonk was supported by an Alzheimer Nederland Fellowship (WE.15-2018-05), ZonMw Veni grant (project number 09150161810017), and NIH K99/R00 Pathway to Independence award (NIA K99AG066934). We thank Paulien Wiersma, Librarian Medical Sciences at University Utrecht, for her help in preparing the systematic search strategy. Publisher Copyright: © 2023
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Alzheimer's disease (AD) is the most common cause of dementia, characterized by the aggregation of amyloid-beta (Aβ) proteins into plaques. Individuals with AD frequently show mixed pathologies, often caused by cerebral small vessel disease (CSVD), resulting in lesions such as white matter hyperintensities (WMH). The current systematic review and meta-analysis investigated the cross-sectional relationship between amyloid burden and WMH in older adults without objective cognitive impairment. A systematic search performed in PubMed, Embase, and PsycINFO yielded 13 eligible studies. Aβ was assessed using PET, CSF, or plasma measurements. Two meta-analyses were performed: one on Cohen's d metrics and one on correlation coefficients. The meta-analyses revealed an overall weighted small-to-medium Cohen's d of 0.55 (95% CI: 0.31–0.78) in CSF, an overall correlation of 0.31 (0.09–0.50) in CSF, and a large Cohen's d of 0.96 (95% CI: 0.66–1.27) in PET. Only two studies assessed this relationship in plasma, with an effect size of − 0.20 (95% CI: −0.75 to 0.34). These findings indicate a relationship between both amyloid and vascular pathologies in cognitively normal adults in PET and CSF. Future studies should assess the possible relationship of blood amyloid-beta and WMH for broader identification of at risk individuals showing mixed pathology in preclinical stages.
AB - Alzheimer's disease (AD) is the most common cause of dementia, characterized by the aggregation of amyloid-beta (Aβ) proteins into plaques. Individuals with AD frequently show mixed pathologies, often caused by cerebral small vessel disease (CSVD), resulting in lesions such as white matter hyperintensities (WMH). The current systematic review and meta-analysis investigated the cross-sectional relationship between amyloid burden and WMH in older adults without objective cognitive impairment. A systematic search performed in PubMed, Embase, and PsycINFO yielded 13 eligible studies. Aβ was assessed using PET, CSF, or plasma measurements. Two meta-analyses were performed: one on Cohen's d metrics and one on correlation coefficients. The meta-analyses revealed an overall weighted small-to-medium Cohen's d of 0.55 (95% CI: 0.31–0.78) in CSF, an overall correlation of 0.31 (0.09–0.50) in CSF, and a large Cohen's d of 0.96 (95% CI: 0.66–1.27) in PET. Only two studies assessed this relationship in plasma, with an effect size of − 0.20 (95% CI: −0.75 to 0.34). These findings indicate a relationship between both amyloid and vascular pathologies in cognitively normal adults in PET and CSF. Future studies should assess the possible relationship of blood amyloid-beta and WMH for broader identification of at risk individuals showing mixed pathology in preclinical stages.
KW - Alzheimer disease
KW - Amyloid
KW - Dementia
KW - White matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=85159192702&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.arr.2023.101952
DO - https://doi.org/10.1016/j.arr.2023.101952
M3 - Review article
C2 - 37178806
SN - 1568-1637
VL - 88
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 101952
ER -