ABSTRACTBackgroundThe progression of Alzheimer’s Disease (AD) may be tracked by measuring the growth of the ventricular cerebrospinal fluid (vCSF) over time. AD is commonly comorbid with markers of cerebral small vessel disease (SVD), viewed on MRI as white matter hyperintensities (WMH). Larger WMH volumes are correlated with poorer cognitive test scores. Additionally, periventricular WMHs have a proposed relationship to the vCSF.PurposeThis study will examine ventricular expansion and its associations between periventricular/deep WMH and cognition in AD and normal aging.MethodsBaseline and 1-year follow-up data were collected from AD (n=117) and cognitively normal control (NCs; n=49) participants taking part in the Sunnybrook Dementia Study. MRI (1.5T) and scores from both the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS) were assessed at each time point. Volumetric data was generated using a semi-automated pipeline and each individual’s vCSF and WMHs were transformed to an intermediate space to determine volumetric growth. Regressions were used to determine relationships between vCSF growth measures, SVD burden, and cognition, accounting for demographics and individual interscan intervals.ResultsThe AD group displayed 14.6% annual ventricular growth as opposed to NC who had only 11.8% annual growth. AD showed significant growth in vCSF (p < 0.001), a trend toward greater pWMH growth (p = 0.06) and no difference in dWMH growth volumes compared to NC. vCSF growth was positively associated with pWMH (β = 0.32, p < 0.001) but not dWMH growth in AD while in NC it was associated with both pWMH (β = 0.48, p < 0.001) and dWMH growth (β = 0.35, p = 0.02). In AD, vCSF growth was associated with the both the MMSE (β = -0.30, p < 0.001) and the DRS (β = -0.31, p < 0.001) in separate models.ConclusionsThe findings from this study suggest that in just under 1.5 years, the significantly rapid ventricular expansion observed in AD may be closely related to periventricular small vessel disease. As vCSF growth rates are an important biomarker of AD neurodegeneration that corresponds with cognitive decline, future research should further explore atrophy associated with periventricular vasculopathy.Trial RegistrationClinicalTrials.gov, NCT01800214. Registered on 27 February 2013.
Improved version of white matter method for correction of nonuniform intensity in MR images: application to the quantification of rates of brain atrophy in Alzheimer's disease and normal aging