Diffusion tensor imaging (DTI) has been used extensively to investigate white matter (WM) microstructural changes during healthy adult aging. However, WM fibers are known to shrink throughout the lifespan, leading to larger interstitial spaces with age. This could allow more extracellular free water molecules to bias DTI metrics, which are relied upon to provide WM microstructural information. Using a cohort of 212 participants, we demonstrate that WM microstructural changes in aging are potentially less pronounced than previously reported once the free water compartment is eliminated. After free water elimination, DTI parameters show age-related differences that match histological evidence of myelin degradation and debris accumulation. The fraction of free water is further shown to associate better with age than any of the conventional DTI parameters. Our findings suggest that DTI analyses involving free water are likely to yield novel insight into retrospective re-analysis of data and to answer new questions in ongoing DTI studies of brain aging.

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ARS-CoV-2 and its related illness, COVID-19, can affect the lungs and several other organs, even in people who do not experience the "cytokine storm." Specifically, the brain is susceptible to injury after COVID-19, and studies suggest an increased risk of large-vessel stroke and multiple vascular-territory-related infarcts, for example. [1][2][3] Of substantial concern, people may struggle with residual "longhaul" COVID-19 symptoms for weeks or months. Carfì and colleagues 4 reported that more than 80% of 143 patients admitted to hospital with acute COVID-19 experienced at least 1 persistent symptom at 36 days after discharge. A larger study showed that 76% of 1655 patients admitted to hospital reported at least 1 symptom 186 days after discharge. 5 Long-haul COVID-19 symptoms strongly suggest an impact on the brain, either directly or indirectly. Electronic health records from 62 health care organizations and more than 200 000 COVID-19 survivors identified that 1 in 3 people were diagnosed with neurologic or psychiatric conditions in the months after infection. 6 In a systematic review involving almost 48 000 COVID-19 survivors, commonly reported symptoms included fatigue (58%), headache (44%), attention disorder (27%) and dyspnea (24%). 7 Those with long-haul symptoms may experience serious symptoms for more than 6 months. In an international survey estimating the prevalence of symptoms over 7 months after the onset of illness, 45% of the 3762 respondents reported working at a reduced level compared to before their illness, and 22% were no longer working because of health issues. 8