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INTRODUCTION The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. METHODS Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55–86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea‐hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water‐corrected diffusion tensor imaging. RESULTS Higher levels of OSA‐related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. DISCUSSION OSA may contribute to fornix damage and memory dysfunction in MCI. Highlights Sleep apnea‐related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.

Background and purpose The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system. Methods A total of 84 PD patients and 82 normal controls were enrolled. Each participant underwent motor and cognitive assessments. Diffusion tensor imaging was used to detect structural abnormalities in the cBF system. The cBF was segmented using FreeSurfer, and its fiber tract was traced using probabilistic tractography. To provide information on extracellular water accumulation, free‐water fraction (FWf) was quantified. FWf in the cBF and its fiber tract, as well as cortical projection density, were extracted for statistical analyses. Results Patients had significantly higher FWf in the cBF (p < 0.001) and fiber tract (p = 0.021) than normal controls, as well as significantly lower cBF projection in the occipital (p < 0.001), parietal (p < 0.001) and prefrontal cortex (p = 0.005). In patients, a higher FWf in the cBF correlated with worse PIGD score (r = 0.306, p = 0.006) and longer Trail Making Test A time (r = 0.303, p = 0.007). Attentional function (Trail Making Test A) partially mediated the association between FWf in the cBF and PIGD score (indirect effect, a*b = 0.071; total effect, c = 0.256; p = 0.006). Conclusions Our findings suggest that degeneration of the cBF system in PD, from the cBF to its fiber tract and cortical projection, plays an important role in cognitive−motor interaction.

INTRODUCTION Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid‐β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals. METHODS Diffusion free‐water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma‐/PET‐ (NC = 22, MCI = 60), plasma+/PET‐ (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross‐sectionally and the relationships between imaging, plasma and PET biomarkers were assessed. RESULTS Plasma+/PET‐ demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma‐/PET‐. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET‐. Composite brain FW correlated with plasma Aβ42/40 and p‐tau181. DISCUSSION FW imaging changes distinguish plasma Aβ42/40 positive and negative groups, independent of group differences in cognitive status, Aβ PET status, and other plasma biomarkers (i.e., t‐tau, p‐tau181, glial fibrillary acidic protein, neurofilament light). Highlights Plasma Aβ42/40 positivity is associated with brain microstructure decline. Plasma+/PET‐ demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET‐ demonstrated decreased FAt in 66 total GM and WM regions. Whole‐brain FW correlated with plasma Aβ42/40 and p‐tau181 measures. Plasma+/PET‐ demonstrated decreased cortical volume and thickness.

INTRODUCTION Free‐water imaging of the choroid plexus (CP) may improve the evaluation of Alzheimer's disease (AD). METHODS Our study investigated the role of free‐water fraction (FWf) of CP in AD among 216 participants (133 Aβ+ participants and 83 Aβ– controls) enrolled in the NeuroBank‐Dementia cohort at Ruijin Hospital (RJNB‐D). The Alzheimer's Disease Neuroimaging Initiative dataset was used for external validation. RESULTS At baseline, Aβ+ participants showed higher CP FWf, increased white matter hyperintensity (WMH) volume, and decreased diffusion tensor image analysis along the perivascular space (DTI‐ALPS). In Aβ+ participants, DTI‐ALPS mediated the association between CP FWf and periventricular WMH. CP FWf was associated with cortical tau accumulation, synaptic loss, hippocampal and cortical atrophy, and cognitive performance. During follow‐up, CP FWf increased faster in Aβ+ participants than controls. DISCUSSION Elevated CP FWf indicated impaired glymphatic function and AD neurodegeneration, and can be a sensitive biomarker for AD progression. The study was registered on ClinicalTrials.gov (NCT05623124). Highlights This cohort study found higher free‐water fraction (FWf) of the choroid plexus (CP) in amyloid beta (Aβ)+ participants. CP FWf was related to glymphatic function, brain atrophy, tau burden, synaptic loss, and cognition. Aβ+ participants showed faster growth of CP FWf than Aβ– controls during follow‐up. The growth rate of CP FWf exceeded that of white matter lesion and tau accumulation in Aβ+ participants. CP FWf can serve as a sensitive imaging marker of glymphatic function and Alzheimer's disease progression.

Although free‐water diffusion reconstruction for diffusion‐weighted imaging (DWI) data can be applied to both single‐shell and multishell data, recent finding in synthetic data suggests that the free‐water indices from single‐shell acquisition should be interpreted with care, as they are heavily influenced by initialization parameters and cannot discriminate between free‐water and mean diffusivity modifications. However, whether using a longer multishell acquisition protocol significantly improve reconstruction for real human MRI data is still an open question. In this study, we compare canonical diffusion tensor imaging (DTI), single‐shell and multishell free‐water imaging (FW) indices derived from a short, clinical compatible diffusion protocol (b = 500 s/mm2, b = 1,000 s/mm2, 32 directions each) on their power to predict brain age. Age was chosen as it is well‐known to be related to widespread modification of the white matter and because brain‐age estimation has recently been found to be relevant to several neurodegenerative diseases. We used a previously developed and validated data‐driven whole‐brain machine learning pipeline to directly compare the precision of brain‐age estimates in a sample of 89 healthy males between 20 and 85 years old. We found that multishell FW outperform DTI indices in estimating brain age and that multishell FW, even when using low (500 ms2) b‐values secondary shell, outperform single‐shell FW. Single‐shell FW led to lower brain‐age estimation accuracy even of canonical DTI indices, suggesting that single‐shell FW indices should be used with caution. For all considered reconstruction algorithms, the most discriminant indices were those measuring free diffusion of water in the white matter. Multishell but not single‐shell free‐water diffusion imaging predicts brain age better than canonical diffusion imaging. Multishell free‐water in isolation performs similarly to more complex models including FA, MD, RD and AD.

Background Autism spectrum disorder (ASD) is a lifelong condition that profoundly impacts health, independence, and quality of life. However, research on brain aging in autistic adults is limited, and microstructural variations in white and gray matter remain poorly understood. To address this critical gap, we assessed novel diffusion MRI (dMRI) biomarkers, free water, and free water corrected fractional anisotropy (fwcFA), and mean diffusivity (fwcMD) across 32 transcallosal tracts and their corresponding homotopic grey matter origin/endpoint regions of interest (ROIs) in middle and old aged autistic adults. Methods Forty-three autistic adults aged 30–73 and 43 age-, sex-, and IQ-matched neurotypical controls underwent dMRI scans. We examined free water, fwcFA, fwcMD differences between the two groups and age-related pattern of each dMRI metric across the whole brain for each group. The relationships between clinical measures of ASD and free water in regions that significantly differentiated autistic adults from neurotypical controls were also explored. In supplementary analyses, we also assessed free water uncorrected FA and MD using conventional single tensor modeling. Results Autistic adults exhibited significantly elevated free water in seven frontal transcallosal tracts compared to controls. In controls, age-related increases in free water and decreases in fwcFA were observed across most transcallosal tracts. However, these age-associated patterns were entirely absent in autistic adults. In gray matter, autistic adults showed elevated free water in the calcarine cortices and lower fwcMD in the dorsal premotor cortices compared to controls. Lastly, age-related increases in free water were found across all white matter and gray matter ROIs in neurotypical controls, whereas no age-related associations were detected in any dMRI metrics for autistic adults. Limitations We only recruited cognitively capable autistic adults, which limits the generalizability of our findings across the full autism spectrum. The cross-sectional design precludes inferences about microstructural changes over time in middle and old aged autistic adults. Conclusions Our findings revealed increased free water load in frontal white matter in autistic adults and identified distinct age-associated microstructural variations between the two groups. These findings highlight more heterogeneous brain aging profiles in autistic adults. Our study also demonstrated the importance of quantifying free water in dMRI studies of ASD.

Background Sinks in patient rooms are associated with hospital-acquired infections. The aim of this study was to evaluate the effect of removal of sinks from the Intensive Care Unit (ICU) patient rooms and the introduction of ‘water-free’ patient care on gram-negative bacilli colonization rates. Methods We conducted a 2-year pre/post quasi-experimental study that compared monthly gram-negative bacilli colonization rates pre- and post-intervention using segmented regression analysis of interrupted time series data. Five ICUs of a tertiary care medical center were included. Participants were all patients of 18 years and older admitted to our ICUs for at least 48 h who also received selective digestive tract decontamination during the twelve month pre-intervention or the twelve month post-intervention period. The effect of sink removal and the introduction of ‘water-free’ patient care on colonization rates with gram-negative bacilli was evaluated. The main outcome of this study was the monthly colonization rate with gram-negative bacilli (GNB). Yeast colonization rates were used as a ‘negative control’. In addition, colonization rates were calculated for first positive culture results from cultures taken ≥3, ≥5, ≥7, ≥10 and ≥14 days after ICU-admission, rate ratios (RR) were calculated and differences tested with chi-squared tests. Results In the pre-intervention period, 1496 patients (9153 admission days) and in the post-intervention period 1444 patients (9044 admission days) were included. Segmented regression analysis showed that the intervention was followed by a statistically significant immediate reduction in GNB colonization in absence of a pre or post intervention trend in GNB colonization. The overall GNB colonization rate dropped from 26.3 to 21.6 GNB/1000 ICU admission days (colonization rate ratio 0.82; 95%CI 0.67–0.99; P  = 0.02). The reduction in GNB colonization rate became more pronounced in patients with a longer ICU-Length of Stay (LOS): from a 1.22-fold reduction (≥2 days), to a 1.6-fold (≥5 days; P  = 0.002), 2.5-fold (for ≥10 days; P  < 0.001) to a 3.6-fold (≥14 days; P  < 0.001) reduction. Conclusions Removal of sinks from patient rooms and introduction of a method of ‘water-free’ patient care is associated with a significant reduction of patient colonization with GNB, especially in patients with a longer ICU length of stay.

The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings; however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively.

Introduction Free‐water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET). Methods Seventy‐one participants underwent multi‐shell diffusion MRI, 18F‐THK5351 PET, 11C‐Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) (n = 40) and AD‐spectrum group (AD‐S) (n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores. Results In AD‐S group, there was a significant positive correlation between FW and 18F‐THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18F‐THK5351 and cognitive function in the same regions. Discussion FW imaging could be a biomarker for tau in AD alongside clinical correlations.

Introduction It is unclear how rates of white matter microstructural decline differ between normal aging and abnormal aging. Methods Diffusion MRI data from several well‐established longitudinal cohorts of aging (Alzheimer's Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], Vanderbilt Memory & Aging Project [VMAP]) were free‐water corrected and harmonized. This dataset included 1723 participants (age at baseline: 72.8 ± 8.87 years, 49.5% male) and 4605 imaging sessions (follow‐up time: 2.97 ± 2.09 years, follow‐up range: 1–13 years, mean number of visits: 4.42 ± 1.98). Differences in white matter microstructural decline in normal and abnormal agers was assessed. Results While we found a global decline in white matter in normal/abnormal aging, we found that several white matter tracts (e.g., cingulum bundle) were vulnerable to abnormal aging. Conclusions There is a prevalent role of white matter microstructural decline in aging, and future large‐scale studies in this area may further refine our understanding of the underlying neurodegenerative processes. HIGHLIGHTS Longitudinal data were free‐water corrected and harmonized. Global effects of white matter decline were seen in normal and abnormal aging. The free‐water metric was most vulnerable to abnormal aging. Cingulum free‐water was the most vulnerable to abnormal aging.