Lower Locus Coeruleus Integrity Signals Elevated Entorhinal Tau and Clinical Progression in Asymptomatic Older Individuals.

OBJECTIVE: Elevated entorhinal cortex (EC) tau in low beta-amyloid individuals can predict accumulation of pathology and cognitive decline. We compared the accuracy of magnetic resonance imaging (MRI)-derived locus coeruleus integrity, neocortical beta-amyloid burden by positron emission tomography (PET), and hippocampal volume in identifying elevated entorhinal tau signal in asymptomatic individuals who are considered beta-amyloid PET-negative. METHODS: We included 188 asymptomatic individuals (70.78 ± 11.51 years, 58% female) who underwent 3T-MRI of the locus coeruleus, Pittsburgh compound-B (PiB), and Flortaucipir (FTP) PET. Associations between elevated EC tau and neocortical PiB, hippocampal volume, or locus coeruleus integrity were evaluated and compared using logistic regression and receiver operating characteristic analyses in the PiB- sample with a clinical dementia rating (CDR) of 0. Associations with clinical progression (CDR-sum-of-boxes) over a time span of 6 years were evaluated with Cox proportional hazard models. RESULTS: We identified 26 (21%) individuals with high EC FTP in the CDR = 0/PiB- sample. Locus coeruleus integrity was a significantly more sensitive and specific predictor of elevated EC FTP (area under the curve [AUC] = 85%) compared with PiB (AUC = 77%) or hippocampal volume (AUC = 76%). Based on the Youden-index, locus coeruleus integrity obtained a sensitivity of 77% and 85% specificity. Using the resulting locus coeruleus Youden cut-off, lower locus coeruleus integrity was associated with a two-fold increase in clinical progression, including mild cognitive impairment. INTERPRETATION: Locus coeruleus integrity has promise as a low-cost, non-invasive screening instrument to detect early cortical tau deposition and associated clinical progression in asymptomatic, low beta-amyloid individuals. ANN NEUROL 2024.

Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition.

Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.

Brain structural indicators of ß-amyloid neuropathology.

Recent efforts demonstrated the efficacy of identifying early-stage neuropathology of Alzheimer's disease (AD) through lumbar puncture cerebrospinal fluid assessment and positron emission tomography (PET) radiotracer imaging. These methods are effective yet are invasive, expensive, and not widely accessible. We extend and improve the multiscale structural mapping (MSSM) procedure to develop structural indicators of ß-amyloid neuropathology in preclinical AD, by capturing both macrostructural and microstructural properties throughout the cerebral cortex using a structural MRI. We find that the MSSM signal is regionally altered in clear positive and negative cases of preclinical amyloid pathology (N = 220) when cortical thickness alone or hippocampal volume is not. It exhibits widespread effects of amyloid positivity across the posterior temporal, parietal, and medial prefrontal cortex, surprisingly consistent with the typical pattern of amyloid deposition. The MSSM signal is significantly correlated with amyloid PET in almost half of the cortex, much of which overlaps with regions where beta-amyloid accumulates, suggesting it could provide a regional brain 'map' that is not available from systemic markers such as plasma markers.

MRI Assessment of Cerebral White Matter Microvascular Hemodynamics Across the Adult Lifespan.

BACKGROUND: Changes in cerebral hemodynamics with aging are important for understanding age-related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter. PURPOSE: To investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP-A) cohort using tract-based spatial statistics (TBSS). STUDY TYPE: Retrospective cross-sectional. POPULATION: Six hundred seventy-eight typically aging individuals (381 female), aged 36-100 years. FIELD STRENGTH/SEQUENCE: Multi-delay pseudo-continuous arterial spin labeling (ASL) and diffusion-weighted pulsed-gradient spin-echo echo planar imaging sequences at 3.0 T. ASSESSMENT: A skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL-derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts. STATISTICAL TESTS: General linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold-free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at PFWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at PFDR < 0.05. RESULTS: Significantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (PFDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA. DATA CONCLUSION: This study identified significant sex- and age-associated differences in white matter hemodynamics across tracts. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Aberrant vascular architecture in the hippocampus correlates with tau burden in mild cognitive impairment and Alzheimer's disease.

Cerebrovascular dysfunction is a significant contributor to Alzheimer's disease (AD) progression. AD mouse models show altered capillary morphology, density, and diminished blood flow in areas of tau and beta-amyloid accumulation. The purpose of this study was to examine alterations in vascular structure and their contributions to perfusion deficits in the hippocampus in AD and mild cognitive impairment (MCI). Seven individuals with AD and MCI (1 AD/6 MCI), nine cognitively intact older healthy adults, and seven younger healthy adults underwent pseudo-continuous arterial spin labeling (PCASL) and gradient-echo/spin-echo (GESE) dynamic susceptibility contrast (DSC) MRI. Cerebral blood flow (CBF), cerebral blood volume, relative vessel size index (rVSI), and mean vessel density were calculated from model fitting. Lower CBF from PCASL and SE DSC MRI was observed in the hippocampus of AD/MCI group. rVSI in the hippocampus of the AD/MCI group was larger than that of the two healthy groups (FDR-P = 0.02). No difference in vessel density was detected between the groups. We also explored relationship of tau burden from 18F-flortaucipir positron emission tomography and vascular measures from MRI. Tau burden was associated with larger vessel size and lower CBF in the hippocampus. We postulate that larger vessel size may be associated with vascular alterations in AD/MCI.

Early onset adolescent binge drinking is associated with reduced white matter integrity in post-9/11 adult veterans.

Adolescence represents a critical period of neural development during which binge drinking (BD) is prevalent. Though prior work has shown that white matter (WM) integrity is susceptible to damage from excessive alcohol intake in adults, the effect of early adolescent BD on WM health in adulthood remains unknown. Veterans with a history of BD onset before age 15 [n = 49; mean age = 31.8 years; early-onset adolescent binge drinkers (EBD)] and after age 15 [n = 290; mean age = 32.2 years; late-onset adolescent binge drinkers (LBD)] were studied with diffusion tensor imaging. Group differences in fractional anisotropy (FA; movement of water molecules along the WM) and mean diffusivity (MD; average movement of water molecules) were examined as indices of WM integrity using FreeSurfer and FMRIB Software Library (FSL) processing streams. Lower FA and higher MD are thought to represent degradations in WM integrity. A reference group (RG) of social drinkers with no history of BD (n = 31) was used to provide comparative normative data. We observed widespread decreased FA and increased MD in EBDs, compared to LBDs, as well as decreased FA in the pars triangularis, lateral orbitofrontal cortex, superior frontal cortex, isthmus cingulate, and genu and splenium of the corpus callosum EBDs also had lower WM integrity compared to the RG. Adults who initiated BD during early adolescence demonstrated decreased FA and increased MD throughout the frontostriatal circuits that mediate inhibitory control and thus may result in impulsive behavior and a predisposition for developing alcohol use disorder during adulthood.

Cardiovascular and metabolic health is associated with functional brain connectivity in middle-aged and older adults: Results from the Human Connectome Project-Aging study.

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and superior temporal regions. Additionally, at the network-level, FC between core brain networks, such as default-mode and cingulo-opercular, as well as dorsal attention networks, showed strong effects of cardiometabolic risk. These findings highlight the lifespan impact of cardiovascular and metabolic health on whole-brain functional integrity and how these conditions may disrupt higher-order network integrity.

Associations between age, sex, APOE genotype, and regional vascular physiology in typically aging adults.

Altered blood flow in the human brain is characteristic of typical aging. However, numerous factors contribute to inter-individual variation in patterns of blood flow throughout the lifespan. To better understand the mechanisms behind such variation, we studied how sex and APOE genotype, a primary genetic risk factor for Alzheimer's disease (AD), influence associations between age and brain perfusion measures. We conducted a cross-sectional study of 562 participants from the Human Connectome Project - Aging (36 to >90 years of age). We found widespread associations between age and vascular parameters, where increasing age was associated with regional decreases in cerebral blood flow (CBF) and increases in arterial transit time (ATT). When grouped by sex and APOE genotype, interactions between group and age demonstrated that females had relatively greater CBF and lower ATT compared to males. Females carrying the APOEε4 allele showed the strongest association between CBF decline and ATT incline with age. This demonstrates that sex and genetic risk for AD modulate age-associated patterns of cerebral perfusion measures.

Mean Arterial Pressure and Cerebral Hemodynamics Across The Lifespan: A Cross-Sectional Study From Human Connectome Project-Aging.

BACKGROUND: Cerebral perfusion is directly affected by systemic blood pressure, which has been shown to be negatively correlated with cerebral blood flow (CBF). The impact of aging on these effects is not fully understood. PURPOSE: To determine whether the relationship between mean arterial pressure (MAP) and cerebral hemodynamics persists throughout the lifespan. STUDY TYPE: Retrospective, cross-sectional study. POPULATION: Six hundred and sixty-nine participants from the Human Connectome Project-Aging ranging between 36 and 100+ years and without a major neurological disorder. FIELD STRENGTH/SEQUENCE: Imaging data was acquired at 3.0 Tesla using a 32-channel head coil. CBF and arterial transit time (ATT) were measured by multi-delay pseudo-continuous arterial spin labeling. ASSESSMENT: The relationships between cerebral hemodynamic parameters and MAP were evaluated globally in gray and white matter and regionally using surface-based analysis in the whole group, separately within different age groups (young: <60 years; younger-old: 60-79 years; oldest-old: ≥80 years). STATISTICAL TESTS: Chi-squared, Kruskal-Wallis, ANOVA, Spearman rank correlation and linear regression models. The general linear model setup in FreeSurfer was used for surface-based analyses. P < 0.05 was considered significant. RESULTS: Globally, there was a significant negative correlation between MAP and CBF in both gray (ρ = -0.275) and white matter (ρ = -0.117). This association was most prominent in the younger-old [gray matter CBF (ß = -0.271); white matter CBF (ß = -0.241)]. In surface-based analyses, CBF exhibited a widespread significant negative association with MAP throughout the brain, whereas a limited number of regions showed significant prolongation in ATT with higher MAP. The associations between regional CBF and MAP in the younger-old showed a different topographic pattern in comparison to young subjects. DATA CONCLUSION: These observations further emphasize the importance of cardiovascular health in mid-to-late adulthood for healthy brain aging. The differences in the topographic pattern with aging indicate a spatially heterogeneous relationship between high blood pressure and CBF. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

The link between static and dynamic brain functional network connectivity and genetic risk of Alzheimer's disease.

Apolipoprotein E (APOE) polymorphic alleles are genetic factors associated with Alzheimer's disease (AD) risk. Although previous studies have explored the link between AD genetic risk and static functional network connectivity (sFNC), to the best of our knowledge, no previous studies have evaluated the association between dynamic FNC (dFNC) and AD genetic risk. Here, we examined the link between sFNC, dFNC, and AD genetic risk with a data-driven approach. We used rs-fMRI, demographic, and APOE data from cognitively normal individuals (N = 886) between 42 and 95 years of age (mean = 70 years). We separated individuals into low, moderate, and high-risk groups. Using Pearson correlation, we calculated sFNC across seven brain networks. We also calculated dFNC with a sliding window and Pearson correlation. The dFNC windows were partitioned into three distinct states with k-means clustering. Next, we calculated the proportion of time each subject spent in each state, called occupancy rate or OCR and frequency of visits. We compared both sFNC and dFNC features across individuals with different genetic risks and found that both sFNC and dFNC are related to AD genetic risk. We found that higher AD risk reduces within-visual sensory network (VSN) sFNC and that individuals with higher AD risk spend more time in a state with lower within-VSN dFNC. We also found that AD genetic risk affects whole-brain sFNC and dFNC in women but not men. In conclusion, we presented novel insights into the links between sFNC, dFNC, and AD genetic risk.

Intimate partner violence and brain imaging in women: A neuroimaging literature review.

PRIMARY OBJECTIVE: Despite a high prevalence of intimate partner violence (IPV) and its lasting impacts on individuals, particularly women, very little is known about how IPV may impact the brain. IPV is known to frequently result in traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). In this overview of literature, we examined literature related to neuroimaging in women with IPV experiences between the years 2010-2021. RESEARCH DESIGN: Literature overview. METHODS AND PROCEDURES: A total of 17 studies were included in the review, which is organized into each imaging modality, including magnetic resonance imaging (structural, diffusion, and functional MRI), Electroencephalography (EEG), proton magnetic resonance spectroscopy (pMRS), and multimodal imaging. MAIN OUTCOMES AND RESULTS: Research has identified changes in brain regions associated with cognition, emotion, and memory. Howeverto date, it is difficult to disentangle the unique contributions of TBI and PTSD effects of IPV on the brain. Furthermore, experimental design elements differ considerably among studies. CONCLUSIONS: The aim is to provide an overview of existing literature to determine commonalities across studies and to identify remaining knowledge gaps and recommendations for implementing future imaging studies with individuals who experience IPV.

Disrupted Dynamic Functional Network Connectivity Among Cognitive Control Networks in the Progression of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from resting-state functional magnetic resonance imaging. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations. Methods: Group independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states, and then estimated a hidden Markov model and the occupancy rate for each subject. Then, we investigated the link between CCN dFC features and AD progression. Also, we investigated the link between sFC and AD progression and compared its results with dFC results. Results: Progression of AD symptoms was associated with increases in connectivity within the middle frontal gyrus. Also, the very mild AD (vmAD) showed less connectivity within the inferior parietal lobule (in both sFC and dFC) and between this region and the rest of CCN (in dFC analysis). Also, we found that within-middle frontal gyrus connectivity increases with AD progression in both sFC and dFC results. Finally, comparing with vmAD, we found that the normal brain spends significantly more time in a state with lower within-middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease. Conclusion: Our results suggest that AD progress not only alters the CCN connectivity strength but also changes the temporal properties in this brain network. This suggests the temporal and spatial pattern of CCN as a biomarker that differentiates different stages of AD.

African ancestry GWAS of dementia in a large military cohort identifies significant risk loci.

While genome wide association studies (GWASs) of Alzheimer's Disease (AD) in European (EUR) ancestry cohorts have identified approximately 83 potentially independent AD risk loci, progress in non-European populations has lagged. In this study, data from the Million Veteran Program (MVP), a biobank which includes genetic data from more than 650,000 US Veteran participants, was used to examine dementia genetics in an African descent (AFR) cohort. A GWAS of Alzheimer's disease and related dementias (ADRD), an expanded AD phenotype including dementias such as vascular and non-specific dementia that included 4012 cases and 18,435 controls age 60+ in AFR MVP participants was performed. A proxy dementia GWAS based on survey-reported parental AD or dementia (n = 4385 maternal cases, 2256 paternal cases, and 45,970 controls) was also performed. These two GWASs were meta-analyzed, and then subsequently compared and meta-analyzed with the results from a previous AFR AD GWAS from the Alzheimer's Disease Genetics Consortium (ADGC). A meta-analysis of common variants across the MVP ADRD and proxy GWASs yielded GWAS significant associations in the region of APOE (p = 2.48 × 10-101), in ROBO1 (rs11919682, p = 1.63 × 10-8), and RNA RP11-340A13.2 (rs148433063, p = 8.56 × 10-9). The MVP/ADGC meta-analysis yielded additional significant SNPs near known AD risk genes TREM2 (rs73427293, p = 2.95 × 10-9), CD2AP (rs7738720, p = 1.14 × 10-9), and ABCA7 (rs73505251, p = 3.26 × 10-10), although the peak variants observed in these genes differed from those previously reported in EUR and AFR cohorts. Of the genes in or near suggestive or genome-wide significant associated variants, nine (CDA, SH2D5, DCBLD1, EML6, GOPC, ABCA7, ROS1, TMCO4, and TREM2) were differentially expressed in the brains of AD cases and controls. This represents the largest AFR GWAS of AD and dementia, finding non-APOE GWAS-significant common SNPs associated with dementia. Increasing representation of AFR participants is an important priority in genetic studies and may lead to increased insight into AD pathophysiology and reduce health disparities.

Gray to white matter signal ratio as a novel biomarker of neurodegeneration in Alzheimer's disease.

Alzheimer's disease (AD) is characterized neuropathologically by ß-amyloid (Aß) plaques, hyperphosphorylated tau neurofibrillary tangles, and neurodegeneration, which lead to a phenotypically heterogeneous cognitive-behavioral dementia syndrome. Our understanding of how these neuropathological and neurodegeneration biomarkers relate to each other is still evolving. A relatively new approach to measuring structural brain change, gray matter to white matter signal intensity ratio (GWR), quantifies the signal contrast between these tissue compartments, and has emerged as a promising marker of AD-related neurodegeneration. We sought to validate GWR as a novel MRI biomarker of neurodegeneration in 29 biomarker positive individuals across the atypical syndromic spectrum of AD. Bivariate correlation analyses revealed that GWR was associated with cortical thickness, tau PET, and amyloid PET, with GWR showing a larger magnitude of abnormality than cortical thickness. We also found that combining GWR, cortical thickness, and amyloid PET better explained observed tau PET signal than using these modalities alone, suggesting that the three imaging biomarkers contribute independently and synergistically to explaining the variance in the distribution of tau pathology. We conclude that GWR is a uniquely sensitive in vivo marker of neurodegenerative change that reflects pathological mechanisms which may occur prior to cortical atrophy. By using all of these imaging biomarkers of AD together, we may be better able to capture, and possibly predict, AD neuropathologic changes in vivo. We hope that such an approach will ultimately contribute to better endpoints to evaluate the efficacy of therapeutic interventions as we move toward an era of disease-modifying treatments for this devastating disease.

Classification of white matter lesions and characteristics of small vessel disease markers.

OBJECTIVES: Radiological markers for cerebral small vessel disease (SVD) may have different biological underpinnings in their development. We attempted to categorize SVD burden by integrating white matter signal abnormalities (WMSA) features and secondary presence of lacunes, microbleeds, and enlarged perivascular spaces. METHODS: Data were acquired from 610 older adults (aged > 40 years) who underwent brain magnetic resonance imaging exam as part of a health checkup. The WMSA were classified individually by the number and size of non-contiguous lesions, distribution, and contrast. Age-detrended lacunes, microbleeds, and enlarged perivascular space were quantified to further categorize individuals. Clinical and laboratory values were compared across the individual classes. RESULTS: Class I was characterized by multiple, small, deep WMSA but a low burden of lacunes and microbleeds; class II had large periventricular WMSA and a high burden of lacunes and microbleeds; and class III had limited juxtaventricular WMSA and lacked lacunes and microbleeds. Class II was associated with older age, diabetes, and a relatively higher neutrophil-to-lymphocyte ratio. Smoking and higher uric acid levels were associated with an increased risk of class I. CONCLUSION: The heterogeneity of SVD was categorized into three classes with distinct clinical correlates. This categorization will improve our understanding of SVD pathophysiology, risk stratification, and outcome prediction. KEY POINTS: • Classification of white matter signal abnormality (WMSA) features was associated with different characteristic of lacunes, microbleeds, and enlarged perivascular space and clinical variability. • Class I was characterized by multiple, small, deep WMSA but a low burden of lacunes and microbleeds. Class II had large periventricular WMSA and a high burden of lacunes and microbleeds. Class III had limited juxtaventricular WMSA and lacked lacunes and microbleeds. • Class II was associated with older age, diabetes, and higher neutrophil-to-lymphocyte ratio. Smoking and higher uric acid levels were associated with an increased risk of class I.

A two-step clustering-based pipeline for big dynamic functional network connectivity data.

Dynamic functional network connectivity (dFNC) estimated from resting-state functional magnetic imaging (rs-fMRI) studies the temporal properties of FNC among brain networks by putting them into distinct states using the clustering method. The computational cost of clustering dFNCs has become a significant practical barrier given the availability of enormous neuroimaging datasets. To this end, we developed a new dFNC pipeline to analyze large dFNC data without accessing hug processing capacity. We validated our proposed pipeline and compared it with the standard one using a publicly available dataset. We found that both standard and iSparse kmeans generate similar dFNC states while our approach is 27 times faster than the traditional method in finding the optimum number of clusters and creating better clustering quality.

Two-step clustering-based pipeline for big dynamic functional network connectivity data.

Background: Dynamic functional network connectivity (dFNC) estimated from resting-state functional magnetic imaging (rs-fMRI) studies the temporally varying functional integration between brain networks. In a conventional dFNC pipeline, a clustering stage to summarize the connectivity patterns that are transiently but reliably realized over the course of a scanning session. However, identifying the right number of clusters (or states) through a conventional clustering criterion computed by running the algorithm repeatedly over a large range of cluster numbers is time-consuming and requires substantial computational power even for typical dFNC datasets, and the computational demands become prohibitive as datasets become larger and scans longer. Here we developed a new dFNC pipeline based on a two-step clustering approach to analyze large dFNC data without having access to huge computational power. Methods: In the proposed dFNC pipeline, we implement two-step clustering. In the first step, we randomly use a sub-sample dFNC data and identify several sets of states at different model orders. In the second step, we aggregate all dFNC states estimated from all iterations in the first step and use this to identify the optimum number of clusters using the elbow criteria. Additionally, we use this new reduced dataset and estimate a final set of states by performing a second kmeans clustering on the aggregated dFNC states from the first k-means clustering. To validate the reproducibility of results in the new pipeline, we analyzed four dFNC datasets from the human connectome project (HCP). Results: We found that both conventional and proposed dFNC pipelines generate similar brain dFNC states across all four sessions with more than 99% similarity. We found that the conventional dFNC pipeline evaluates the clustering order and finds the final dFNC state in 275 min, while this process takes only 11 min for the proposed dFNC pipeline. In other words, the new pipeline is 25 times faster than the traditional method in finding the optimum number of clusters and finding the final dFNC states. We also found that the new method results in better clustering quality than the conventional approach (p < 0.001). We show that the results are replicated across four different datasets from HCP. Conclusion: We developed a new analytic pipeline that facilitates the analysis of large dFNC datasets without having access to a huge computational power source. We validated the reproducibility of the result across multiple datasets.

Oxygen extraction efficiency and white matter lesion burden in older adults exhibiting radiological evidence of capillary shunting.

White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer's disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60-80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEFmax) with dynamic susceptibility contrast, and WML volume with T1-weighted MRI. We found a significant interaction between OEFmax and VHS presence on WML volume (p = 0.02), where lower OEFmax was associated with higher WML volume in participants with VHS, and higher OEFmax was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.

Open-source FlexNIRS: A low-cost, wireless and wearable cerebral health tracker.

Currently, there is great interest in making neuroimaging widely accessible and thus expanding the sampling population for better understanding and preventing diseases. The use of wearable health devices has skyrocketed in recent years, allowing continuous assessment of physiological parameters in patients and research cohorts. While most health wearables monitor the heart, lungs and skeletal muscles, devices targeting the brain are currently lacking. To promote brain health in the general population, we developed a novel, low-cost wireless cerebral oximeter called FlexNIRS. The device has 4 LEDs and 3 photodiode detectors arranged in a symmetric geometry, which allows for a self-calibrated multi-distance method to recover cerebral hemoglobin oxygenation (SO2) at a rate of 100 Hz. The device is powered by a rechargeable battery and uses Bluetooth Low Energy (BLE) for wireless communication. We developed an Android application for portable data collection and real-time analysis and display. Characterization tests in phantoms and human participants show very low noise (noise-equivalent power <70 fW/√Hz) and robustness of SO2 quantification in vivo. The estimated cost is on the order of $50/unit for 1000 units, and our goal is to share the device with the research community following an open-source model. The low cost, ease-of-use, smart-phone readiness, accurate SO2 quantification, real time data quality feedback, and long battery life make prolonged monitoring feasible in low resource settings, including typically medically underserved communities, and enable new community and telehealth applications.

The canonical pattern of Alzheimer's disease atrophy is linked to white matter hyperintensities in normal controls, differently in normal controls compared to in AD.

White matter signal abnormalities (WMSA), either hypo- or hyperintensities in MRI imaging, are considered a proxy of cerebrovascular pathology and contribute to, and modulate, the clinical presentation of Alzheimer's disease (AD), with cognitive dysfunction being apparent at lower levels of amyloid and/or tau pathology when lesions are present. To what extent the topography of cortical thinning associated with AD may be explained by WMSA remains unclear. Cortical thickness group difference maps and subgroup analyses show that the effect of WMSA on cortical thickness in cognitively normal participants has a higher overlap with the canonical pattern of AD, compared to AD participants. (Age and sex-matched group of 119 NC (AV45 PET negative, CDR = 0) versus 119 participants with AD (AV45 PET-positive, CDR > 0.5). The canonical patterns of cortical atrophy thought to be specific to Alzheimer's disease are strongly linked to cerebrovascular pathology supporting a reinterpretation of the classical models of AD suggesting that a part of the typical AD pattern is due to co-localized cortical loss before the onset of AD.