Keywords: Aging, Brain

Motivation: Studies have shown that presbycusis is associated with cognitive impairment.

Goal(s): To study the pathophysiological mechanism of presbycusis and its potential association with cognitive impairment.

Approach: To study the levels of auditory γ-aminobutyric acid (GABA) and glutamate (Glu), cerebral blood flow (CBF) and their relationship with auditory and cognitive function in patients with presbycusis and healthy controls. 

Results: The results showed that the decrease of auditory GABA, Glu levels and CBF in presbycusis was related to the decrease of speech perception or cognitive impairment, and mediated the association between hearing loss and impaired information processing speed in presbycusis.

Impact: The decrease of GABA and CBF mediates the correlation between hearing loss and impaired information processing speed in presbycusis, which helps us to reveal the relationship between hearing loss and cognitive impairment in presbycusis.

Keywords: Aging, Neurodegeneration

Motivation: Studies have shown a correlation between cardiovascular health and the size of the hippocampus. However, how cardiovascular conditions impact blood flow and vessel health in the brain, and how this potentially affects hippocampus, is still not fully understand

Goal(s): We tested whether hippocampal vascularization statistically mediates the association of multiple cardiovascular risk factors and hippocampal volumes in each hemisphere.

Approach: Hippocampal vascularization was segmented from T1-weighted MPRAGE images at 7T. Mediation analysis was performed to test the relationship between various cardiovascular variables and hippocampal volume via hippocampal vascularization

Results: Hippocampal vascularization statistically mediates the association between cardiovascular health and hippocampal volume

Impact: understanding the exact causal pathways between cardiovascular outcomes, hippocampal vascularization, and hippocampal volume is crucial for establish novel strategies for potentially mitigating the risk of cognitive decline and cerebrovascular diseases

Keywords: Aging, Oxygenation

Motivation: While links between microvascular physiology and white matter lesion burden have largely been studied in older adults with high vascular risk, some individuals exhibit high lesion burden despite presenting with low vascular risk.

Goal(s): To determine whether associations between hemo-metabolic physiology and lesion burden vary in older adults according to vascular risk.

Approach: We compared MRI-based measures of oxygen supply and oxygen extraction fraction (OEF) between older adults categorized by vascular risk and white matter lesion burden.

Results: In low-risk individuals, OEF was uniquely lower in the subgroup with higher lesion burden, while oxygen supply did not differ between the subgroups.

Impact: Impaired oxygen extraction may represent an important and independent contributor to white matter lesion burden in older adults in whom lesion burden is high despite the absence of conventional vascular risk factors.

Keywords: Aging, Perfusion, Aging brains

Motivation: Age-related changes of arterial transit time (ATT) and perfusion (CBF) measurement in hippocampus subfields is still under-investigated.

Goal(s): To quantitatively characterize the age-related hippocampal perfusion changes in a subfield-specific manner to better understand its involvement in neurodegenerative changes and dementia.

Approach: T1-weighted images and mbPCASL data from the Human Connectome Project-Aging (HCA) was analyzed to obtain subfield-specific measurements of ATT and CBF in hippocampus.

Results: The lowest perfusion measurement was observed in CA1 region across all age groups. Age trajectories of CBF and ATT were demonstrated in different subfields with female showing a more significant decrease of hippocampal perfusion.

Impact: Using Human Connectome Project–Aging (HCA) dataset, this study revealed age-related subfield-specific changes in hippocampal ATT and CBF across the adult normative lifespan, including subiculum, CA1-CA4 and the dentate gyrus.

Keywords: Aging, Metabolism, CMRO2, perfusion, gender aspects, IQ, lifestyle, multi-contrast, oxygen extraction fraction

Motivation: Metabolic aspects of brain ageing and normal functioning in the elderly, especially gender-specific, are still insufficiently understood. Lifestyle influences are thought important, but proper quantification of their effect is pending.

Goal(s): To investigate correlations between metabolic function, age and lifestyle.

Approach: Brain oxygen metabolism reflected by CMRO2 and OEF as well as circulatory aspects (CBF and venous blood fraction) are measured by MRI in an elderly cohort characterised by lifestyle and IQ information. 

Results: Gender-specific correlations between metabolism/circulation and age, lifestyle and IQ are found. Their differences suggest different adaptation mechanisms of men and women to the challenges of ageing.

Impact: Metabolic and circulatory parameters of the ageing brain show correlations with gender and lifestyle, besides age. Gender differences, strongest in OEF, are attributed to effects of menopause and different adaptation mechanisms. We find correlations of IQ with metabolism and circulation.

Keywords: Aging, High-Field MRI

Motivation: LSA plays an important role in the pathology of small vessel disease. Directly assessing LSA pulsatility may offer valuable insight into SVD pathology.

Goal(s): To assess the utility of 7T dual-VENC PC-MRI for the LSA pulsatility assessment in elderly adults by investigating its association with age and cognitive impairment.

Approach: LSA pulsatility was assessed using 7T PC-MRI using both dual- and single-VENC on 25 elderly participants. Cognitive tests including MMSE and MOCA were conducted.

Results: Our results showed that the LSA pulsatility was significantly correlated with upstream major arteries and increased LSA pulsatility was associated with aging, education level, and cognitive impairment. 

Impact: Increased LSA pulsatility measured by dual-VENC PC-MRI shows a strong association with aging, education, and cognitive impairment. Compared to single-VENC, dual-VENC PC-MRI enhanced the detection and characterization of LSAs, providing a promising imaging tool for investigating vascular pathology of SVD.

Keywords: Aging, Neurodegeneration

Motivation: Currently, the primary MRI-based biomarker for cognitive dysfunction is the atrophy of medial-temporal-lobe (MTL). However, MTL atrophy represents a late stage of tissue damage. Functional biomarkers such as the MTL oxygen metabolism may be more sensitive in early stages.

Goal(s): To evaluate the association of MTL oxygen metabolism with cognitive function in non-demented elderly individuals.

Approach: We used a novel MRI technique to evaluate the MTL oxygen metabolism in 48 elderly subjects. Cognitive function of the participants was assessed.

Results: Worse cognitive scores were associated with elevated oxygen extraction and metabolic rate in the MTL, but not with the volume of MTL.

Impact: Our findings indicated that measuring the oxygen extraction and metabolic rate in the medial temporal lobe may be more sensitive than structural atrophy in detecting tissue damage in early stages of cognitive impairment.

Keywords: Aging, Aging

Motivation: Structural brain ageing models are associated with cognitive decline, and the addition of arterial spin labelling (ASL)-derived improved brain-age estimation accuracy, but the relation between cerebrovascular ageing and cognitive decline is not yet fully understood.

Goal(s): To assess the contribution of ASL in the relationship between brain-age estimates and cognitive decline.

Approach: Brain-age estimation accuracy and linear relationships with composite cognitive scores were compared between structural-only (T1w and FLAIR), ASL-only, and structural+ASL models.

Results: Combined structural and ASL brain-age models showed the highest accuracy and increased effect sizes with composite cognitive scores, however, ASL-only models showed unexpected relationships.

Impact: Combined structural-ASL brain-age models might present a surrogate biomarker in an earlier stage of cognitive decline, aiding in diagnosis and treatment monitoring. Possible mediation effects of ASL on the association of structural decline with cognitive domains should be investigated further.

Keywords: Aging, Aging, Brain, modelling, metabolism, arterial spin labeling, neurovascular coupling, oxygen extraction fraction

Motivation: How loss of vascular health in aging leads to loss of brain function remains unexplained, since paradoxically brain energy consumption is close to normal.

Goal(s): Our goal is to determine whether the loss of vascular health impacts the tissue accumulation of metabolic nutrients and waste products, which may interfere with brain function.

Approach: We exploited Homeostatic Modeling to obtain brain maps of pCO2, pO2 and pH from two retrospective PET and MRI datasets.

Results: Our results show that reduced vascular health in the elderly leads to regional loss of pCO₂, pO₂, and pH homeostasis of potential clinical significance.

Impact: Determining whether impaired vascular health results into loss of homeostasis of metabolic waste products is critical to guide interventions that improve or preserve brain health in aging and beyond, including neurological conditions such as dementia, stroke, and traumatic brain injury.

Keywords: Aging, Aging

Motivation: Cerebral metabolic rate of oxygen (CMRO₂) reflects the brain’s energy consumption and neural function. Longitudinal CMRO₂ changes in the aging brain have not been fully characterized.

Goal(s): Our goal was to study longitudinal CMRO₂ changes in cognitively normal older adults and examine differences in CMRO₂ between participants without and with cognitive impairment.

Approach: CMRO₂ was estimated from MRI measurements. Linear mixed effect (LME) models were employed to evaluate the relationship between CMRO₂ and the related independent variables.

Results: CMRO₂ decreased with age cross-sectionally and increased with follow-up time longitudinally. CMRO₂ was lower in cognitively impaired participants compared to cognitively normal participants.

Impact: The present work revealed a bell-shaped trajectory of CMRO₂ in aging. CMRO₂ may also be a promising biomarker of neurogenerative diseases. 

Keywords: Aging, Microstructure

Motivation: While vessel architecture mapping (VAM) is an emerging quantitative MR imaging technique that can characterize cerebral blood vessel microstructure in vivo based on dynamic changes in gradient-echo and spin-echo relaxation rates during contrast agent administration, no study has examined how age-related morphological changes affect VAM parameters.

Goal(s): Our goal was to assess region-specific age- and sex-related changes in cerebral microvasculature with VAM.

Approach: We applied high-resolution VAM on the healthy contralateral hemisphere of 72 age-matched women and men with stable low-grade brain tumors.

Results: We could show that microvascular morphology and aging-related remodeling differ between sexes, particularly in thalamus, insular cortex, and putamen.

Impact: This is the first study to characterize age- and sex-specific changes in cerebral microvascular architecture across different anatomical regions using vascular architecture mapping. Results may be of particular importance for future studies on sex-specific diagnostics and prevention of cerebrovascular disease.

Keywords: Aging, Aging

Motivation: In clinical work, there is an urgent need to understand the changes in CBF in different brain regions of normal elderly people to detect abnormalities.

Goal(s): to investigate and understand age-related changes in CBF values measured using ASL in different brain regions of the elderly

Approach: we recruited 344 healthy elderly participants and employed ASL magnetic resonance imaging to measure CBF values in multiple brain regions. We segmented the brain into distinct ROIs and quantified CBF values for each ROI.

Results: CBF reduction was manifested in some areas.Overall brain CBF decreases in both sexes begin at age 60 years

Impact: provides valuable insights into age-related alterations in CBF values measured using ASL in different brain regions of the elderly. Understanding these changes is crucial for developing strategies to support healthy brain aging and prevent cognitive decline in older populations

Keywords: Dementia, Neurodegeneration, Biomarkers, Diagnosis/Prediction

Motivation: Small-vessel-disease (SVD), a contributing risk factor in vascular cognitive impairment and dementia (VCID), needs sensitive biomarkers to assess the brain.

Goal(s): Our goal is to evaluate whether gas-free cerebrovascular reactivity (CVR) can predict cognitive function in older individuals.

Approach: We performed gas-free CVR mapping with intermittent breath modulation in two studies of elderly individuals and evaluated the relationship between gas-free CVR and global cognition.

Results: Higher whole-brain gas-free CVR was correlated with better MoCA scores.

Impact: Gas-free cerebrovascular reactivity (CVR) using intermittent breath modulation can be used as a practical tool to evaluate cerebrovascular function and probe vascular pathology in small-vessel-disease (SVD) and vascular cognitive impairment and dementia (VCID).

Keywords: Other Neurodegeneration, Arterial spin labelling, Hydrocephalus, cerebral blood flow, cerebral blood flow regulation, hemodynamics

Motivation: It is unclear whether the 3D pCASL with dual PLDs can reflect blood flow (CBF) regulation in hydrocephalus patients.

Goal(s): To investigate hemodynamic characteristics in patients with hydrocephalus and whether ΔCBF can reflect cerebral regulation.

Approach: Patients with hydrocephalus and control subjects were retrospectively included. Regional CBF and ΔCBF were compared using covariance analyses. The relationship between ΔCBF and ventricular dilatation degree was investigated using linear regression analyses and interaction analysis.

Results: Compared to the control group, hydrocephalus patients showed larger ΔCBF in all brain regions except for the bilateral parietal cortex and cerebellum.

Impact: Patients with hydrocephalus initiate cerebral regulation to maintain CBF but require longer arterial transit times. The ability to regulate CBF in brain regions represented by the watershed is associated with the degree of ventricular dilation.

Keywords: Other Neurodegeneration, Arterial spin labelling, post concussion syndrome

Motivation: The clinical relevance and modifications in perfusion and neural activity remain undetermined in Post-Concussive Syndrome.

Goal(s): To delineate changes in NVC during the pathophysiology of PCS, multimodal magnetic resonance imaging was performed on patients and healthy controls.

Approach: Five imaging-markers elucidates the relationship between neuronal activity and perfusion. Dynamic causal modeling  evaluates associations with disease transitions, clinical variables, and information flow.

Results: The fALFF-CBF of the hippocampal was diminished, and the ReHo-CBF in the Temporal-Occipital cortex decreased, correlating with declining spatial processing and memory tasks.

Impact: The distinctive pattern of changes in neurovascular coupling in the hippocampal , temporal-occipital cortex provide fresh insights into PCS

Keywords: Other Neurodegeneration, Diabetes, neurovascular coupling; fMRI; cerebral blood flow

Motivation: The neurovascular coupling is the basic structure of neurovascular unit. Various pathological injuries lead to abnormalities in neuronal activity and blood flow resulting in impaired function. There is still not much research on the coupling pattern. 

Goal(s): We hypothesize that there exists an abnormal NVC pattern for T2DM. 

Approach: We recruited 40 patients clinically diagnosed with T2DM, healthy controls and underwent BOLD fMRI scanning and image analysis.

Results: Results found significant decreased CBF-ALFF ratio in supramarginal and frontal gyrus, and increased values in middle frontal gyrus of T2DM. The ALFF and CBF was found to be reduced or elevated in several brain regions.

Impact: In addition to the frontal and parietal gyrus, the cerebellum is also involved in the mechanisms of brain function impairment in T2DM. The different coupling results indicate the existence of mutually constraining balancing mechanism between neural activity and blood perfusion.