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White matter hyperintensities predicted Alzheimer’s disease diagnosis
Amyloid plaque deposits and increased signal intensity in the brain’s white matter — or white matter hyperintensities — each independently predicted Alzheimer’s disease diagnosis, according to a team of neuroscientists.
Amyloid plaque deposits are a pathologic hallmark of Alzheimer’s disease, but white matter hyperintensities represent a clinical marker typically associated with small vessel cerebrovascular disease that has not previously been considered a core feature of Alzheimer’s. The findings suggest an opportunity for earlier prevention and treatment.
“Small vessel cerebrovascular changes play an important role in the clinical presentation of Alzheimer's disease,” study researcher Adam M. Brickman, PhD, of Columbia University, told Psychiatric Annals. “Prevention and treatment of vascular risk factors may help mitigate the severity of the disease.”
Adam M. Brickman
Amyloid deposits alone are not enough to diagnose Alzheimer’s disease since healthy individuals may have elevated levels of the plaque, as well. In fact, the Society of Nuclear Medicine and Molecular Imaging and the Alzheimer’s Association recently issued guidelines to restrict use of amyloid positron emission tomography (PET) in living patients suspected of having Alzheimer’s disease, urging physicians to use the method only when the detection of amyloid plaques would increase certainty in the diagnosis and inform treatment options.
Brickman and colleagues examined data from the Alzheimer’s disease Neuroimaging Initiative (ADNI) to determine how amyloid plaque deposits and white matter hyperintensities (WMHs) interacted to predict Alzheimer’s disease. The study included 20 patients with Alzheimer’s disease, 21 healthy patients and 59 patients with mild cognitive impairment. The researchers used the imaging agent Pittsburgh Compound B (PIB), which binds to and helps visualize amyloid plaque deposits. Patients’ PET scans were downloaded from the ADNI database.
A total of 28 (68%) participants were classified as PIB positive. Of those, 17 met clinical criteria for Alzheimer’s disease. Thirteen participants were PIB negative, of whom 3 met criteria for Alzheimer’s disease (P=.03). WMH volume (P=.02) and PIB positivity (P=.049) were each independently associated with Alzheimer’s disease diagnosis. In patients who were PIB positive, increased signal intensity was associated with Alzheimer’s disease (P=.05).
Among patients with mild cognitive impairment, both WMH volume and PIB-positive status at baseline were associated with increased risk for future diagnosis of Alzheimer’s disease (P=.006), suggesting that small-vessel cerebrovascular disease may play a role in the development of the disorder, according to the researchers.
Brickman and colleagues noted that the ADNI study excluded participants with any significant medical morbidity. Despite this, white matter hyperintensities were still significantly associated with Alzheimer’s disease diagnosis.
“The association between WMHs and clinical [Alzheimer’s disease] among individuals without a significant medical history also suggests that WMHs may reflect pathologic changes that are not restricted to small-vessel cerebrovascular disease,” they wrote. “For example, WMHs may to some degree point to underlying inflammatory changes to vascular forms of [beta]-amyloid itself.”
Disclosure: Brickman reports no relevant financial disclosures.