TABLE 1.

Summary of findings.

Outcomes	Summary of findings	Comment
Longevity	Strong evidence for longevity in e2	E2 appears to have a strong effect, perhaps independent of its effects on AD.
Neuropathology	Circumscribed protective effects of e2 on AD-related neuropathologies (less accumulation of amyloid and tau aggregates)	E2 exhibits a protective effect with reduced Aβ, neuritic plaque, and NFT; however, e2 may promote risk for certain FTLDs and tauopathies, as well as cerebral amyloid angiopathy.
Cognition	Weak and inconsistent evidence for e2 effect	Stronger findings in longitudinal datasets and in clinical populations (MCI and AD), but findings are considered inconclusive due to heterogeneous methods.
Neuroimaging
Structural MRI	Weak and inconsistent evidence for e2 effect	Stronger findings in longitudinal datasets and in clinical populations (MCI and AD), but findings are inconclusive due to heterogeneous methods.
Amyloid PET	Strong evidence for reduced PET Aβ with e2	Findings were similar across cross-sectional and longitudinal analyses, as well as in healthy controls and in MCI and AD.
White matter hyperintensities (WMH)	Strong evidence for increased WMH in e2	Findings were consistent with t other cerebrovascular tissue and vessel pathologies.
Diffusor tensor imaging (DTI)	Weak and inconsistent evidence for e2 effect	Very few studies have been conducted, making meaningful interpretations difficult.
Functional imaging	Weak and inconsistent evidence for e2 effect	Age and AD pathology may alter the relationship between e2 and functional connectivity.
CSF biomarkers	Strong evidence for the effect of e2 on lower CSF Aβ but inconsistent findings for CSF tau	Findings corroborated neuropathology literatures for Aβ, but not for tau. The reasons for this are obscure.