Cardio-metabolic risk factors and cortical thickness in a neurologically healthy male population: results from the psychological, social and biological determinants of ill health (pSoBid) study

<p>Introduction: Cardio-metabolic risk factors have been associated with poor physical and mental health. Epidemiological studies have shown peripheral risk markers to be associated with poor cognitive functioning in normal healthy population and in disease. The aim of the study was to explore the relationship between cardio-metabolic risk factors and cortical thickness in a neurologically healthy middle aged population-based sample.</p> <p>Methods: T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness in 40 adult males (average age = 50.96 years), selected from the PSOBID study. The relationship between cardio-vascular risk markers and cortical thickness across the whole brain, were examined using the general linear models. The relationship with various covariates of interest was explored.</p> <p>Results: Lipid fractions with greater triglyceride content (TAG, VLDL and LDL) were associated with greater cortical thickness pertaining to a number of regions in the brain. Greater C reactive protein (CRP) and Intercellular adhesion molecule (ICAM-1) levels were associated with cortical thinning pertaining to perisylvian regions in the left hemisphere. Smoking status and education status were significant covariates in the model.</p> <p>Conclusions: This exploratory study adds to a small body of existing literature increasingly showing a relationship between cardio-metabolic risk markers and regional cortical thickness involving a number of regions in the brain in a neurologically normal middle aged sample. A focused investigation of factors determining the inter-individual variations in regional cortical thickness in the adult brain could provide further clarity in our understanding of the relationship between cardio-metabolic factors and cortical structures.</p&gt

Mechanisms linking obesity and its metabolic comorbidities with cerebral grey and white matter changes

Obesity is a preventable risk factor for cerebrovascular disorders and it is associated with cerebral grey and white matter changes. Specifically, individuals with obesity show diminished grey matter volume and thickness, which seems to be more prominent among fronto-temporal regions in the brain. At the same time, obesity is associated with lower microstructural white matter integrity, and it has been found to precede increases in white matter hyperintensity load. To date, however, it is unclear whether these findings can be attributed solely to obesity or whether they are a consequence of cardiometabolic complications that often co-exist with obesity, such as low-grade systemic inflammation, hypertension, insulin resistance, or dyslipidemia. In this narrative review we aim to provide a comprehensive overview of the potential impact of obesity and a number of its cardiometabolic consequences on brain integrity, both separately and in synergy with each other. We also identify current gaps in knowledge and outline recommendations for future research

Central adiposity and brain vulnerability in mid-life : evidence for early risk

This set of projects focused on visceral fat, measured using proximal and direct methods. Specifically, I was interested in the effects of visceral fat on brain structure and integrity in middle age. Study 1 looked at waist to hip ratio (WHR) as a proximal measure of visceral fat and used statistical mediation to directly examine a possible mechanism behind the relationship between visceral fat and cognitive decline. Reductions in executive function seen in middle-aged adults with high visceral fat were found to occur in the context of lowered serum brain derived neurotrophic factor (BDNF) a key neurotrophin involved in synaptic plasticity as well as neuronal regeneration. Study 2 utilized Dual Energy X Ray Absorptiometry (DXA) to directly estimate visceral fat mass and volume as well as thickness of the cortical mantle in middle age. High-resolution Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE) images were used. High visceral fat was found to predict increased thickness in the posterior cingulate cortex independently of age and cardiovascular risk in a cognitively intact middle-aged sample. Study 3 examined changes in concentrations of crucial cerebral metabolites in the posterior cingulate cortex among individuals with high visceral fat. Results indicated that visceral fat predicted reduced concentrations of N Acetyl Asparate, a marker of neuronal viability and increased concentrations of myo-inositol, a glial marker that is implicated in a number of disease states including prodromal Alzheimer’s Disease and Multiple Sclerosis. Collectively, the 3 studies highlight important evidence for early brain vulnerability even in cognitively intact middle- aged adults with high levels of cognitive reserve. An important next step would be to examine modifiable mediators of these relationships, such as inflammation and BDNF so that targeted interventions may be developed.Psycholog

Interleukin-6, age, and corpus callosum integrity.

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories

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\u27s 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

Clinical and neuroimaging prognostic markers in Alzheimer's Disease and Lewy Body Dementia: The role of muscle status and nutrition

Alzheimer's Disease and Lewy body dementia are the two most common neurodegenerative dementias. They have a progressive course with devastating consequences for the people living with these diseases and their families, but there are large individual variations. Finding early markers and markers of progression and prognosis could promote actions to improve the quality of life of the people affected with these diseases. Nutrition and muscle status are closely related and have systemic functions and interactions that affect the brain. This thesis describes the role of nutritional and muscle status biomarkers in the prognosis of people diagnosed with mild Alzheimer's disease, Lewy body dementia, and mild subjective cognitive decline. Methods For the aim of this thesis, I used data from 2 community-based prospective Norwegian multicenter cohort studies: DemVest (The Dementia Study of Western Norway) and DDI (Dementia Disease Initiation). In DemVest, patients with mild dementia, defined as a Mini-Mental Status Examination (MMSE) score; equal or higher to 20 or Clinical Dementia Rating (CDR) global score equal to 1, with different types of dementia, were included. The DDI study was designed to investigate early cognitive impairment and dementia markers. DDI participants included in this thesis were those classified as having Subjective cognitive decline (SCD) according to the SCD-I framework. Comprehensive clinical assessments, including measures of cognition, daily functioning and anthropometric measurement, blood samples, and brain MRI were performed in both studies. Brain morphology was studied using FreeSurfer segmentation and muscle morphology using slice O-Matic software. Results This thesis findings first indicate that nutritional status has an essential role in the 5-year prognosis of people living with dementia in the capacity to perform daily life activities and mortality. Second, the quality of the muscle, here the muscle of the tongue, and its amount of fat infiltration were associated with malnutrition onset in people with dementia. Finally, in patients with SCD, muscle function measured with the timed up and go test (TUG) was associated with cognitive decline. TUG, in addition, was associated with cortical thickness in areas related with cognitive and motor functioning. Conclusion Nutritional and muscular status predict prognosis in people with SCD and with dementia. These findings suggest that interventions focused on these areas may improve outcomes such as cognition, function, and survival in these groups

Coronectomy of deeply impacted lower third molar : incidence of outcomes and complications after one year follow-up

Objectives: The purpose of present study was to assess the surgical management of impacted third molar with proximity to the inferior alveolar nerve and complications associated with coronectomy in a series of patients undergoing third molar surgery. Material and Methods: The position of the mandibular canal in relation to the mandibular third molar region and mandibular foramen in the front part of the mandible (i.e., third molar in close proximity to the inferior alveolar nerve [IAN] or not) was identified on panoramic radiographs of patients scheduled for third molar extraction. Results: Close proximity to the IAN was observed in 64 patients (35 females, 29 males) with an impacted mandibular third molar. Coronectomy was performed in these patients. The most common complication was tooth migration away from the mandibular canal (n = 14), followed by root exposure (n = 5). Re-operation to remove the root was performed in cases with periapical infection and root exposure. Conclusions: The results indicate that coronectomy can be considered a reasonable and safe treatment alternative for patients who demonstrate elevated risk for injury to the inferior alveolar nerve with removal of the third molars. Coronectomy did not increase the incidence of damage to the inferior alveolar nerve and would be safer than complete extraction in situations in which the root of the mandibular third molar overlaps or is in close proximity to the mandibular canal

Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults

Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed with neuroimaging. Objectives: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals. Methods: Seventy-one subjects (ages: 55 to 76; apnea–hypopnea index: 0.2 to 96.6 events/h) were evaluated with magnetic resonance imaging. Two techniques were used: 1) voxel-based morphometry, which measures gray matter volume and concentration; 2) FreeSurfer automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, sleep fragmentation). Measurements and Main Results: Subjects had few symptoms, i.e. sleepiness, depression, anxiety and cognitive deficits. While no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume while more severe sleep fragmentation was associated with increased thickness of the inferior frontal gyrus. Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea

The neuroprotective effects of endurance training on the aging brain

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known and may relate to alterations in brain structure (e.g. cortical atrophy) and/or altered neural function, particularly in regions related to the cortical autonomic network, namely, the medial prefrontal cortex (MPFC), insula cortex (IC), and hippocampus (HC). Exercise exerts beneficial effects on brain structure and, in the case of cognition, neurologic function; however, how exercise affects regions of the brain related to autonomic function are not known. This thesis tested the hypothesis that changes in autonomic outflow across the adult age-span are related to cerebral cortex atrophy and function, and are sensitive to the effects of physical fitness. Study 1 demonstrated that advancing age impairs the heart rate (HR) response and modifies the cortical patterns associated with cardiovascular control during isometric handgrip (IHG), and is further exacerbated with coronary artery disease. The utility of aerobic exercise to prevent these age-related changes is not known. Study 2 revealed that lifelong, sustained aerobic training builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span, but did not alter the rate of age-related cortical or subcortical decline. Study 3 demonstrated that cardiorespiratory fitness correlated strongly with whole-brain cortical thickness, while markers of autonomic outflow were specifically associated with cortical mass at the MPFC. Importantly, the strength of the relationship between autonomic variables and cortical thickness was determined by age, and was not altered following adjustments for cardiorespiratory fitness. Study 4 revealed a positive effect of high fitness on MPFC activation, yet did not affect absolute HR responses to IHG in this age range. Therefore, this series of studies implicates cortical atrophy in the frontal lobe as a contributor to the dysregulation of autonomic outflow associated with advancing age, and suggests that high cardiorespiratory fitness delays the age-related decline in cortical circuitry associated with cardiovascular control