White matter hyperintensities are associated with subthreshold amyloid accumulation.

Area of Science:

• Neurology
• Neuroimaging
• Gerontology

Background:

• White matter hyperintensities (WMH) are common in aging but their association with early amyloid pathology in cognitively normal individuals is unclear.
• Amyloid accumulation is a key pathological hallmark of Alzheimer's disease, detectable years before cognitive decline.

Purpose of the Study:

• To investigate the relationship between baseline white matter hyperintensities (WMH) and longitudinal amyloid accumulation in cognitively normal, amyloid-negative elderly participants.
• To determine if baseline WMH burden predicts future subthreshold amyloid deposition.

Main Methods:

• 159 cognitively normal, amyloid-negative participants from the Alzheimer's Disease Neuroimaging Initiative underwent MRI and amyloid PET scans.
• Longitudinal amyloid PET imaging over 8 years, with partial volume correction applied to quantify cortical Standardised Uptake Value Ratios (SUVR).
• Linear mixed models assessed associations between baseline WMH (global and regional) and amyloid accumulation rates.

Main Results:

• No significant correlation between baseline WMH and baseline amyloid uptake was observed.
• Increased baseline burden of global, frontal, and parietal WMH was significantly associated with faster longitudinal amyloid accumulation (p < 0.01).
• Amyloid accumulation related to WMH was most prominent in parietal and frontal cortices.

Conclusions:

• Baseline white matter hyperintensities, particularly in frontal and parietal regions, predict future amyloid accumulation in cognitively normal elderly individuals.
• This finding is the first to link specific WMH distributions to subsequent amyloid deposition in preclinical Alzheimer's disease.
• These results have implications for early identification of individuals at risk for Alzheimer's disease in prevention trials.