Background and Objectives The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this system may play a pivotal role in amyloid β (Aβ) accumulation. However, its involvement in Alzheimer disease (AD) pathogenesis is not fully understood. Here, we investigated the changes in noninvasive MRI measurements related to the perivascular network in patients with mild cognitive impairment (MCI) and AD. Additionally, we explored the associations of MRI measures with neuropsychological score, PET standardized uptake value ratio (SUVR), and Aβ deposition. Methods MRI measures, including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer9s Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD. Statistical analyses were performed with age, sex, years of education, and APOE status as confounding factors. Results In total, 36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia PVSVF (Cohen d = 1.15–1.48; p < 0.001) and FW-WM (Cohen d = 0.73; p < 0.05) and a lower ALPS index (Cohen d = 0.63; p < 0.05) than healthy controls. Meanwhile, the MCI group only showed significantly higher total (Cohen d = 0.99; p < 0.05) and WM (Cohen d = 0.91; p < 0.05) PVSVF. Low ALPS index was associated with lower CSF Aβ42 (r_s = 0.41, p_fdr = 0.026), FDG-PET uptake (r_s = 0.54, p_fdr < 0.001), and worse multiple cognitive domain deficits. High FW-WM was also associated with lower CSF Aβ42 (r_s = −0.47, p_fdr = 0.021) and worse cognitive performances. Discussion Our study indicates that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. We also report the associations between MRI parameters and Aβ deposition, neuronal change, and cognitive impairment in AD.

BACKGROUND AND PURPOSE: Hypertension may be related to alterations of the glymphatic system, a waste metabolite drainage system in the brain. We aimed to investigate analysis along the perivascular space index changes in elderly subjects with hypertension. MATERIALS AND METHODS: Diffusion-weighted images were acquired from 126 subjects, including 63 subjects with hypertension (25 men and 38 women; mean age, 72.45 years) and 63 age- and sex-matched controls (25 men and 38 women; mean age, 72.16 years). We calculated the analysis along the perivascular space index as a ratio of the mean of x-axis diffusivities in the projection and association areas to the mean of y-axis diffusivity in the projection area and z-axis diffusivity in the association area. The left, right, and mean analysis along the perivascular space indices of both hemispheres were compared between the hypertension and control groups using a Mann-Whitney U test. The Spearman correlation coefficient was used to assess the correlation between the left, right, and mean ALPS indices and blood pressure and pulse pressure. RESULTS: The left (P = .011) and mean (P = .024) analysis along the perivascular space indices of the hypertension group were significantly lower than that of the control group. The left, right, and mean analysis along the perivascular space indices of all subjects were significantly negatively correlated with blood pressure values (r = −0.200 to −0.278, P = .002–0.046) and pulse pressure values (r = −0.221 to −0.245, P = .006–0.013). CONCLUSIONS: Our results are consistent with a model in which hypertension causes glymphatic dysfunction.

Background: The aim of this study was to evaluate the water diffusivity changes along the perivascular space after lumboperitoneal shunt (LPS) surgery in idiopathic normal pressure hydrocephalus.Methods: Nine patients diagnosed with idiopathic normal pressure hydrocephalus (iNPH; three men and six women, mean age ± SD = 75.22 ± 5.12 years) according to the guidelines for iNPH in Japan were included in the study. Post-LPS surgery, six patients with iNPH who exhibited improvement in symptoms were defined as responder subjects, while three patients with iNPH who did not were defined as non-responder subjects. We calculated the mean analysis along the perivascular space (ALPS) index of the left and right hemispheres and compared the differences between pre- and post-LPS surgery mean ALPS indices in iNPH patients. In the responder or non-responder subjects, the mean ALPS indices in the pre- and post-operative iNPH groups were compared using Wilcoxon signed-rank tests. Next, correlation analyses between pre- and post-operation changes in the mean ALPS index and clinical characteristics were conducted.Results: The mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.021). In responder subjects, the mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.046). On the other hand, in the non-responder subjects, the mean ALPS index of the post-operative iNPH group was not significantly different compared to the pre-operative iNPH group (p = 0.285). The mean ALPS index change was not significantly correlated with changes in the Mini-Mental State Examination (MMSE) score (r = −0.218, p = 0.574), Frontal Assessment Battery (FAB) score (r = 0.185, p = 0.634), Trail Making Test A (TMTA) score (r = 0.250, p = 0.516), and Evans' index (r = 0.109, p = 0.780). In responder subjects, the mean ALPS index change was significantly correlated with Evans' index in pre-operative patients with iNPH (r = 0.841, p = 0.036).Conclusion: This study demonstrates the improved water diffusivity along perivascular space in patients with iNPH after LPS surgery. This could be indicative of glymphatic function recovery following LPS surgery.

Background and Objectives: Integrating large language models (LLMs) such as GPT-4 Turbo into diagnostic imaging faces a significant challenge, with current misdiagnosis rates ranging from 30–50%. This study evaluates how prompt engineering and confidence thresholds can improve diagnostic accuracy in neuroradiology. Methods: We analyze 751 neuroradiology cases from the American Journal of Neuroradiology using GPT-4 Turbo with customized prompts to improve diagnostic precision. Results: Initially, GPT-4 Turbo achieved a baseline diagnostic accuracy of 55.1%. By reformatting responses to list five diagnostic candidates and applying a 90% confidence threshold, the highest precision of the diagnosis increased to 72.9%, with the candidate list providing the correct diagnosis at 85.9%, reducing the misdiagnosis rate to 14.1%. However, this threshold reduced the number of cases that responded. Conclusions: Strategic prompt engineering and high confidence thresholds significantly reduce misdiagnoses and improve the precision of the LLM diagnostic in neuroradiology. More research is needed to optimize these approaches for broader clinical implementation, balancing accuracy and utility.

Background and purpose: Exposure to contact sports in youth causes brain health problems later in life. For instance, the repetitive head impacts in contact sports might contribute to glymphatic clearance impairment and cognitive decline. This study aimed to assess the effect of contact sports participation in youth on glymphatic function in old age and the relationship between glymphatic function and cognitive status using the analysis along the perivascular space (ALPS) index.Materials and methods: A total of 52 Japanese older male subjects were included in the study, including 12 who played heavy-contact sports (mean age, 71.2 years), 15 who played semicontact sports (mean age, 73.1 years), and 25 who played noncontact sports (mean age, 71.3 years) in their youth. All brain diffusion-weighted images (DWIs) of the subjects were acquired using a 3T MRI scanner. The ALPS indices were calculated using a validated semiautomated pipeline. The ALPS indices from the left and right hemispheres were compared between groups using a general linear model, including age and years of education. Furthermore, partial Spearman's rank correlation tests were performed to assess the correlation between the ALPS indices and cognitive scores (Mini-Mental State Examination and the Japanese version of the Montreal Cognitive Assessment [MoCA-J]) after adjusting for age years of education and HbA1c.Results: The left ALPS index was significantly lower in the heavy-contact and semicontact groups than that in the noncontact group. Although no significant differences were observed in the left ALPS index between the heavy-contact and semicontact groups and in the right ALPS index among groups, a trend toward lower was found in the right ALPS index in individuals with semicontact and heavy-contact compared to the noncontact group. Both sides' ALPS indices were significantly positively correlated with the MoCA-J scores.Conclusion: The findings indicated the potential adverse effect of contact sports experience in youth on the glymphatic system function in old age associated with cognitive decline.

The aging process induces a variety of changes in the brain detectable by magnetic resonance imaging (MRI). These changes include alterations in brain volume, fluid-attenuated inversion recovery (FLAIR) white matter hyperintense lesions, and variations in tissue properties such as relaxivity, myelin, iron content, neurite density, and other microstructures. Each MRI technique offers unique insights into the structural and compositional changes occurring in the brain due to normal aging or neurodegenerative diseases. Age-related brain volume changes encompass a decrease in gray matter and an increase in ventricular volume, associated with cognitive decline. White matter hyperintensities, detected by FLAIR, are common and linked to cognitive impairments and increased risk of stroke and dementia. Tissue relaxometry reveals age-related changes in relaxivity, aiding the distinction between normal aging and pathological conditions. Myelin content, measurable by MRI, changes with age and is associated with cognitive and motor function alterations. Iron accumulation, detected by susceptibility-sensitive MRI, increases in certain brain regions with age, potentially contributing to neurodegenerative processes. Diffusion MRI provides detailed insights into microstructural changes such as neurite density and orientation. Neurofluid imaging, using techniques like gadolinium-based contrast agents and diffusion MRI, reveals age-related changes in cerebrospinal and interstitial fluid dynamics, crucial for brain health and waste clearance. This review offers a comprehensive overview of age-related brain changes revealed by various MRI techniques. Understanding these changes helps differentiate between normal aging and pathological conditions, aiding the development of interventions to mitigate age-related cognitive decline and other symptoms. Recent advances in machine learning and artificial intelligence have enabled novel methods for estimating brain age, offering also potential biomarkers for neurological and psychiatric disorders.