Affiliations: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Correspondence:
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Correspondence to: Arnold Bakker, PhD, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street / Phipps 300, Baltimore, MD 21287, USA. Tel.: +1 410 502 6944; E-mail: abakker@jhu.edu.
Abstract: Recently, the field of Alzheimer’s disease (AD) research has adopted a new framework that places the progression of AD along a continuum consisting of a preclinical stage, followed by conversion to mild cognitive impairment, and ultimately dementia. Important neuropathological changes occur in the preclinical phase, necessitating the identification of metrics that can detect such early changes. While cerebrospinal fluid (CSF) measures of amyloid and tau are generally accepted as biomarkers of AD pathology, neuroimaging measures used to index white matter alterations throughout the brain remain less widely endorsed as candidate biomarkers. To explore the relationship between white matter alterations and AD pathology, we review the literature on multimodal studies that assessed both CSF markers and white matter indices, derived from diffusion tensor imaging (DTI) methods, across cohorts primarily in the early phases of AD. Our review indicates that abnormal CSF measures of Aβ42 and tau are associated with widespread alterations in white matter microstructure throughout the brain. Furthermore, white matter variability is related to individual differences in behavior and can aid in tracking longitudinal changes in cognition. Our review advocates for the utilization of DTI metrics in investigations of early AD and suggests that the combined use of DTI and CSF markers may better explain individual differences in cognition and disease progression. However, further research is needed to resolve certain mixed findings.
