The Unique Contribution of White Matter Hyperintensities to Cognitive,
Neuropsychiatric, and Functional Decline in Alzheimer's Disease 
   Lead Investigator:    Christian Puzo
   Institution      :    Boston University
   E-Mail           :    puzoc@bu.edu
   Proposal ID      :    1083


   Publications:


1  Puzo C, Labriola C, Sugarman MA, Tipodis Y, Martin B, Palmisano JN, Steinberg EG, Stein TD, Kowall NW, McKee AC, Mez J, Killiany RJ, Stern RA, Alosco ML
   Independent Effects of White Matter Hyperintensities on Cognitive, Neuropsychiatric, and Functional Decline: A Longitudinal Investigation using the National Alzheimer's Coordinating Center Uniform Dat
   Journal Article  Alzheimers Res Ther,64:epub ahead of p,2019,PMC6661103

   PUBLISHED





   Proposal Description:
   A growing body of research continues to support white matter hyperintensities (WMH), an MRI marker of cerebral small vessel disease (CSVD), as an important predictor of cognitive, psychiatric, functional, and neuropathological changes indicative of neurodegenerative disease. Several studies have demonstrated the ability of WMH to predict both the presence and rate of cognitive decline, as well as conversion from normal cognition to MCI and from MCI to dementia. In addition, greater volume of WMH is associated with neuropsychiatric symptoms, including depression. There is increasing evidence that WMH may also represent a specific MRI biomarker for Alzheimer?s disease. Recent research has demonstrated that higher severity of WMH corresponded to greater odds of displaying Alzheimer?s disease Neuropathology (ADNP). Despite these advances, MRI WMH are non-specific markers of pathology and it has long been debated whether WMH play an additive or mechanistic, or both, role in the clinical and pathological development of AD. To determine the exact relationship between WMH and AD, inclusion of specific biomarkers for underlying AD pathology (e.g.,??-amyloid PET scans, CSF ??-amyloid, phosphorylated tau [p-tau]) is necessary.    The objective of this project is to examine the unique contribution WMH make to the cognitive, psychiatric, and functional changes associated with AD dementia by controlling for traditional biomarkers and risk factors for AD (e.g. hippocampal atrophy, APOE status, CSF markers of beta-amyloid). The current project will evaluate the relationship between WMH and other AD biomarkers, such as CSF biomarkers and ??-amyloid PET scans to determine whether the interaction of WMH with other AD biomarkers can predict the most serious changes in cognitive and neuropsychiatric function found in those with AD. To evaluate this aim, we will need to longitudinally track participants? neuropsychological testing performance, psychiatric symptom history, functional cap