Frontal Lobe Volumes Research Articles

Тривожно-когнітивні розлади у пацієнтів з метаболічним синдромом: клініко-нейровізуалізаційна діагностика, лікування

Мета дослідження: вивчити когнітивний, психоемоційний стан та нейровізуалізаційні показники головного мозку в пацієнтів середнього віку з хронічними формами цереброваскулярних захворювань на фоні метаболічного синдрому; вивчити клінічну ефективність, безпечність, вплив на когнітивні показники, тривогу вітчизняного препарату Вітаксон® у пацієнтів з хронічними формами цереброваскулярних захворювань на фоні метаболічного синдрому. Матеріали і методи. У відкритому контрольованому дослідженні взяли участь 60 пацієнтів віком від 42 до 61 року (Ме = 52 [Q1 = 54; Q3 = 60]) з метаболічним синдромом. Пацієнтам основної групи (n = 30) до базисної терапії додавався препарат Вітаксон®. У контрольній групі (n = 30) пацієнти отримували лише базисну терапію. Критерієм включення в дослідження була наявність тривожно-когнітивних розладів у пацієнтів з дисциркуляторною енцефалопатією І–ІІ ст. на фоні метаболічного синдрому. Проводили клініко-лабораторне обстеження та нейропсихологічне тестування за шкалами: МоСА; Спілбергера; Бека; таблицями Шульте. За допомогою методу волюметрії на МРТ-сканері Toshiba Vantage Titan 1,5 оцінено стан головного мозку в 41 пацієнта. Проводили кореляційний аналіз показників об’єму кори й білої речовини скроневої й лобної часток та когнітивно-тривожних порушень в пацієнтів з метаболічним синдромом та без нього. Результати. Після 24-денного курсу лікування відбулось покращення когнітивних функцій за шкалою МоСА в обох групах (в основній групі — на 1,5 бали; у контрольній — на 0,5 балів), у групі, у якій пацієнти приймали Вітаксон®, відмінності були вірогідними (р < 0,05). Показники реактивної тривожності за шкалою Спілбергера покращились в основній групі (42,4 ± 3,4 бала до лікування та 24,6 ± 2,8 бала на 24-ту добу), у контрольній відповідні показники суттєво не відрізнялись (41,2 ± 3,2 бала та 39,1 ± 2,1 бала відповідно). Аналіз результатів тестування за таблицями Шульте показав вірогідне зменшення показників виконання завдань після лікування в групі, що приймала Вітаксон® (р < 0,05). Показники депресії за шкалою HADS після лікування покращились в обох групах, але ступеня статистичної вірогідності не було досягнуто. Аналіз волюметричних досліджень показав погіршення когнітивних функцій за шкалою МоСА при зменшенні об’єму кори в лобній і скроневій частках. Визначався кореляційний зв’язок між показниками об’єму кори лобної і скроневої часток і результатами когнітивних функцій за шкалою МоСА. Індекс кореляції r = 0,49 для показників скроневої частки та r = 0,43 — для лобних часток. Модулі коефіцієнтів кореляції були середньої сили. Висновки. У пацієнтів з МС визначалось зменшення об’ємів сірої речовини в скроневих і лобних частках, що корелювало з когнітивним дефіцитом за шкалою МоСА. Ці дані свідчать більшою мірою про змішаний характер когнітивних порушень — судинно-дегенеративний. Проведення волюметричного дослідження в поєднанні з нейропсихологічним дозволяє на стадії помірних когнітивних порушень прогнозувати подальший розвиток захворювання. Наявність позитивного нейротропного ефекту на когнітивно-тривожні прояви та відсутність значимих побічних явищ у препарату Вітаксон® дозволяють рекомендувати його для лікування хронічних форм цереброваскулярних захворювань у пацієнтів з метаболічним синдромом.

Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study.

Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 ± 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured serum magnesium and with available MRI scans obtained in 2011–2013, participating in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Cross-sectional differences in frontal, temporal, parietal, and occipital lobe volume, along with deep grey matter, total brain, and white matter hyperintensity volume across serum magnesium (categorized into quintiles and per standard deviation increases) were assessed using multiple linear regression. We also examined associations of magnesium with the prevalence of cortical, subcortical, and lacunar infarcts using multiple logistic regression. After adjusting for demographics, biomarkers, medications, and cardiometabolic risk factors, higher circulating magnesium was associated with greater total brain volume and frontal, temporal, and parietal lobe volumes (volumes 0.14 to 0.19 standard deviations higher comparing Q5 to Q1). Elevated magnesium was also associated with lower odds of subcortical infarcts (OR (95%CI): 0.44 (0.25, 0.77) comparing Q5 to Q1) and lacunar infarcts (OR (95%CI): 0.40 (0.22, 0.71) comparing Q5 to Q1). Elevated serum magnesium was cross-sectionally associated with greater brain volumes and lower odds of subclinical cerebrovascular disease, suggesting beneficial effects on pathways related to neurodegeneration and cerebrovascular damage. Further exploration through prospective analyses is needed to assess increasing circulating magnesium as a potential neuroprotective intervention.

Microglial activation and atrophy in frontal cortex predict executive dysfunction in frontotemporal dementia

AbstractBackgroundFrontotemporal dementia is clinically and neuropathologically heterogeneous, but atrophy, neuroinflammation, and executive dysfunction occur in each of the principal variants. Across the clinical spectrum of frontotemporal dementia, we assessed the predictive value of in vivo neuroimaging measures of grey‐matter volume (from structural MRI) and microglial activation (from [11C]PK11195 PET) on the rate of future executive decline. We hypothesised a detrimental effect of inflammation and atrophy severity on executive dysfunction progression.MethodThirty patients with frontotemporal dementia underwent a baseline multi‐modal imaging assessment, including [11C]PK11195 PET to index microglial activation and structural MRI for atrophy, as part of the Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study. Cognitive impairments were assessed at baseline and serially for up to 5 years with the revised Addenbrooke's Cognitive Examination (ACE‐R). Regional grey‐matter volumes and [11C]PK11195 binding potentials were averaged in four regions of interest: left and right frontal and temporal lobes. Linear mixed models were applied to the longitudinal ACE‐R attention/executive sub‐score. Regional CSF‐corrected PET values and TIV‐corrected grey‐matter volumes were included in linear mixed models as predictors, with age and education as covariates. Specifically, negative associations of atrophy and inflammation with annual rate of executive decline were tested.ResultPatients showed a mean 3.3‐point loss per year on the ACE‐R attention/executive sub‐score (p<0.001, Figure 1). Faster decline in ACE‐R was associated with reduced baseline grey‐matter volume of the left frontal lobe (beta=1.000, SE=0.285, p=0.000789, p‐FDR= 0.00316; Figure 2) and increased inflammation in frontal regions bilaterally (Left: beta=‐0.722, SE=0.251, p=0.00528, p‐FDR=0.0105, Figure 2; Right: Estimate=‐0.623, SE=0.256, p=0.0175, p‐FDR=0.0233). These associations remain significant when including both left frontal grey‐matter volume and [11C]PK11195 binding as predictors in the same model, and after controlling for baseline attention/executive scores. In these regions, grey‐matter volumes and inflammation levels were negatively correlated (left: r=‐0.414, p<0.001; right: r=‐0.374, p<0.001).ConclusionImaging markers for atrophy and microglial activation provide useful and independent information to evaluate and stratify patients with frontotemporal dementia. This may improve cohort selection in clinical trials and highlights the potential for immunomodulatory treatment strategies in frontotemporal dementia.

Apolipoprotein ε genotype modifies the association between blood‐brain barrier permeability and both grey and white matter integrity in older adults

AbstractBackgroundBlood‐brain barrier (BBB) permeability has been implicated in Alzheimer’s disease and is associated with decreased cerebral blood flow and cognitive impairment. However, associations between BBB permeability and structural brain changes remain unknown. This study relates the cerebrospinal fluid (CSF)/plasma albumin ratio, a proxy measure for BBB permeability, to grey matter volumes and white matter integrityMethodVanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=148, 72±6 years, 41% female, 32% apolipoprotein E (APOE) ε4 positive) underwent fasting lumbar puncture for CSF sampling and blood draw for plasma sampling. Participants underwent 3T T1‐weighted imaging to quantify grey matter volumes and diffusion tensor imaging (DTI) to quantify white matter integrity. Voxel‐wise analyses using non‐parametric permutations cross‐sectionally related the CSF/plasma albumin ratio to DTI metrics, adjusting for demographic and health variables, diagnosis, and APOE‐ε4 status. Linear regressions related the CSF/plasma albumin ratio to grey matter volumes, adjusting for identical covariates plus intracranial volume. Follow‐up models tested interactions with APOE‐ε4 status.ResultIn the entire sample, the CSF/plasma albumin ratio was unrelated to grey matter volumes and white matter integrity (p‐values>0.28) but interacted with APOE‐ε4 status on total grey matter (p‐value=0.02), frontal lobe (p‐value=0.01), and occipital lobe volumes (p‐value=0.04). Stratification suggested a higher CSF/plasma albumin ratio, indicating impaired BBB function, related to smaller grey matter volumes among APOE‐ε4 carriers. The CSF/plasma albumin ratio also interacted with APOE‐ε4 status on white matter integrity in the temporal and frontal lobes (p‐values<0.05), with associations present in APOE‐ε4 non‐carriers.ConclusionIncreased BBB permeability is associated with decreased grey matter volume in APOE‐ε4 carriers, specifically in the frontal and occipital lobes. APOE‐ε4 may act as a vascular modifier in these regions, such that increased BBB permeability exacerbates underlying neurotoxicity and neurodegeneration. In contrast, the association between increased BBB permeability and compromised white matter integrity is driven by APOE‐ε4 non‐carriers. Taken together, these results suggest that BBB permeability may be an etiology of neurodegeneration in APOE‐ε4 carriers and highlight the importance of APOE‐ε4 status when studying BBB effects on brain health.

Influence of MRI on Diagnostic Efficacy and Satisfaction of Patients with Alzheimer's Disease.

Objective To inquire into the influence of magnetic resonance imaging (MRI) on the diagnostic efficacy and satisfaction of patients with Alzheimer's disease (AD). Methods This study included 42 healthy people (control group) and 66 patients with AD (AD group). The hippocampus volume, temporal sulcus spacing, left-right brain diameter, brain lobe volume, hippocampal height, temporal horn width, lateral fissure width, and degree of leukoaraiosis were all measured using an MRI scan. After diagnosis, the satisfaction of patients in both arms was investigated and the satisfaction degree was recorded. Results Compared with the control group, the left and right hippocampal volumes and hippocampal height of AD patients were smaller, while the temporal sulcus spacing, temporal horn width, lateral fissure width, and left-right brain diameter were remarkably higher. A statistical difference was present in the degree of leukoaraiosis between the two arms. The frontal and temporal lobe volumes of AD patients were notably lower while the volumes of parietal and occipital lobes were similar, versus the control group. The total satisfaction was 83.33% in the control group and 86.36% in the AD group, with no statistical difference between the two arms. Conclusions MRI can effectively mine the brain information of AD patients with a high patient satisfaction, which has potential value in clinical application.

The Effect of Self-Paced Exercise Intensity and Cardiorespiratory Fitness on Frontal Grey Matter Volume in Cognitively Normal Older Adults: A Randomised Controlled Trial.

Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults. Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention. The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups. At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.

Memory impairment in alcohol use disorder is associated with regional frontal brain volumes

BackgroundEpisodic memory deficits occur in alcohol use disorder (AUD), but their anatomical substrates remain in question. Although persistent memory impairment is classically associated with limbic circuitry disruption, learning and retrieval of new information also relies on frontal systems. Despite AUD vulnerability of frontal lobe integrity, relations between frontal regions and memory processes have been under-appreciated. MethodsParticipants included 91 AUD (49 with a drug diagnosis history) and 36 controls. Verbal and visual episodic memory scores were age- and education-corrected. Structural magnetic resonance imaging (MRI) data yielded regional frontal lobe (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and total hippocampal volumes. ResultsAUD were impaired on all memory scores and had smaller precentral frontal and hippocampal volumes than controls. Orbital, superior, and inferior frontal volumes and lifetime alcohol consumption were independent predictors of episodic memory in AUD. Selectivity was established with a double dissociation, where orbital frontal volume predicted verbal but not visual memory, whereas inferior frontal volumes predicted visual but not verbal memory. Further, superior frontal volumes predicted verbal memory in AUD alone, whereas orbital frontal volumes predicted verbal memory in AUD+drug abuse history. ConclusionsSelective relations among frontal subregions and episodic memory processes highlight the relevance of extra-limbic regions in mnemonic processes in AUD. Memory deficits resulting from frontal dysfunction, unlike the episodic memory impairment associated with limbic dysfunction, may be more amenable to recovery with cessation or reduction of alcohol misuse and may partially explain the heterogeneity in episodic memory abilities in AUD.

Journal Digest: Amygdala and ‘Broken Heart’ Syndrome; Digital Intervention and Paranoia Symptoms; Snoring in Children and Brain Development; Impaired Self-Control and Binge Eating Behavior; HS Football and Midlife Mental Health Problems

Journal Digest: Amygdala and ‘Broken Heart’ Syndrome; Digital Intervention and Paranoia Symptoms; Snoring in Children and Brain Development; Impaired Self-Control and Binge Eating Behavior; HS Football and Midlife Mental Health Problems

The effect of sex and age on cortical grey and white matter volumes of frontal lobe

Grey matter (GM) of the frontal lobe carries out its complex function such as muscle control, speech, decision making, and self-control; while the white matter (WM) of frontal lobe is a major contributor to human brain enlargement and higher structural connectivity. This study was conducted to assess the effect of sex and age on grey and white matter volumes (GMV and WMV) of the frontal lobe and its gyri in healthy young adult Sudanese. The present study included 139 healthy Sudanese subjects (80 males and 59 females). Participant’s ages were ranging between 20-40 years. T1-weighted MR brain images with thickness 1mm were obtained. MR images of the subjects were analyzed using the automatic segmentation software (BrainSuite). GMV and WMV of frontal lobe and its gyri were estimated using the output data of the process of software. Males had greater GMV and WMV of the frontal lobes (251.18±31.80cm3 and 143.48±22.92cm3, respectively) and most of frontal lobe gyri (P&lt;0.05). Change with age in GMV has been reported in the frontal lobes, superior frontal gyrus, pars orbitalis, orbitofrontal, and cingulate gyrus (P&lt;0.05). Change with age in WM volumes has been found in the cingulate, precentral, and paracentral gyri (P&lt;0.05). Sex has prominent effect on GMV and WMV of the frontal lobes and most of frontal lobe gyri, thus sex is a major contributor to GMV and WMV differences between individuals. Age effect GMV and WMV of most frontal lobe gyri, these findings confirm the continuation of maturation of frontal lobe until fourth decade. Assessing effect of sex and age on GM and WM in healthy adult has major importance to distinguish the normal brain from diseased.

ASSOCIATION OF AMBULATORY BLOOD PRESSURE WITH FRONTAL CORTICAL THICKNESS AND HIPPOCAMPAL VOLUME

Objective: In the elderly, the effect of blood pressure on brain structure or cognitive function has not been clear. However, there are limitations in that most of studies was done using serial change in clinic blood pressure. We sought to determine the association of the ambulatory blood pressure over time with the brain structural alterations and cognitive function Design and method: In this study, we sought to examine the association between blood pressure and brain structure/cognitive function in the elderly over the age of 60 by using the 24-hour ambulatory blood pressure information at 2 different visits (mean time interval is 3.4 years). From October 2018, we included participants performed Korean Mini Mental State Exam; older than 60 years old among the participants in Cardiovascular and Metabolic Disease Etiology Research Center-High Risk Cohort. Results: When we divided the 170 participants into two groups according to the control of cumulative average daytime blood pressure, the cortical thickness of frontal lobe was thinner and the average hippocampal volume was smaller in the uncontrolled group (P = 0.002, P = 0.01 respectively). In multivariate linear analysis, the uncontrolled group for cumulative average daytime blood pressure was associated with thinner cortical thickness of frontal lobe and smaller average hippocampal volume (P = 0.007, P = 0.024 respectively). However, the baseline daytime blood pressure had no associations with brain structure or cognitive function. Conclusions: Our observations suggest that serial measurements of 24-hour ambulatory blood pressure may be important to assess the cumulative pressure load and the association with structural changes of the brain.

Impulsivity and Decision-making Style Among Tramadol Drug Addicts and its Relation to Frontal Lobe Volume

Objectives: Drug addiction has its effects on different behavioral and personality traits including impulsivity and pattern of decision-making. The frontal lobe was the focus of many of these studies regarding its important role in decision-making and other higher cognitive processes. We aimed to detect the pattern of decision-making styles and impulsivity among people with tramadol addiction, and also to find out if tramadol addiction has effects on the volume of different regions of the frontal lobe. Materials and Methods: Two groups were included: group A included 12 patients with tramadol addiction and group B included 23 healthy cross-matching controls. Both groups were subjected to urine drug screening, Iowa gambling task (IGT), UPPS scales (negative urgency, lack of perseverance, lack of premeditation, and sensation seeking), and structural magnetic resonance imaging brain study. Results: The patients’ group has shown a significantly lower volume of the brain white matter, gray matter, and cortical thickness (P&lt;0.001). This group has also shown a significantly higher scores of IGT-A and IGT-B (P&lt;0.001 and P=0.02, respectively) and has shown a higher score of all subscales of UPPS. Conclusions: Tramadol addiction is associated with a reduced volume of the brain white matter, gray matter, and cortical thickness. All regions of the frontal lobe have shown significant volume reduction in the tramadol group. Tramadol addiction and its duration are associated with risky decision-making style and with higher impulsivity than nonaddicts.

Household physical activity is positively associated with gray matter volume in older adults

BackgroundTotal physical activity is positively associated with brain volume and cognition in older adults. While we have ample evidence that recreational physical activity influences brain health, the contributions of other daily activities are less understood. In particular, the associations between household physical activity and brain health in older adults is underexplored. The purpose of this study was to identify associations between household physical activity, brain volume, and cognition in a sample of cognitively unimpaired older adults.MethodsWe report data from 66 cognitively unimpaired older adults (71 ± 4 years) who participated in a health evaluation, cognitive assessment, and structural brain imaging. Physical activity was assessed using the Phone-FITT questionnaire and separated into household and recreational physical activity. We quantified whole brain volume, gray matter volume, and white matter volume, and assessed cognitive performance in four domains: memory, working memory/attention, processing speed, and executive function. Associations between physical activity, brain volume, and cognition were investigated in an omnibus approach using two multivariate analysis of variance (MANOVA) models. The first model assessed the associations between physical activity and brain volume adjusting for age, sex, Framingham Risk score (FRS) and intracranial volume. The second model assessed the associations between physical activity and overall cognitive performance adjusting for age, sex, FRS and education. Post hoc regression analyses were conducted to investigate significant MANOVA results. We also conducted further regression analyses to investigate associations with hippocampal and frontal lobe volume.ResultsHousehold, but not recreational, physical activity was positively associated with brain volume measurements (F = 3.07, p = .035), specifically gray matter volume (t = 2.51, p = .015). Further exploratory analyses identified that household physical activity was associated with hippocampal (p = .015) and frontal lobe (p = .010) volume. No significant relationships were observed between household or recreational physical activity and cognition.ConclusionTime spent engaging in household physical activity was positively associated with brain volume, specifically gray matter volume, in older adults. Highlighting the benefits associated with household chores may motivate older adults to be more active by providing a more attainable, low risk form of physical activity.

Dual-Task Gait Cost and Frontal Lobe Integrity in Poststroke: Results From ONDRI

Dual-task gait performance is a marker of motor-cognitive interactions modulated by the frontal lobes. After a stroke, gait disturbances are more evident, particularly when concurrently completing a mental task and walking, an effect called high dual-task cost (DTC). Following a stroke, the potential association of high-DTC, integrity of the frontal lobes and cognitive functioning is unclear. This study screened 161 participants with stroke history from the Ontario Neurodegenerative Disease Research Initiative (ONDRI)-cerebrovascular disease cohort (69.2±7.41 years of age; 31.7% women). Individuals scoring zero in the National Institute of Health Stroke Scale were analyzed (n=102). DTC was the percentage change in gait speed from the single to dual-task condition. Standardized normal-appearing white matter (NAWM) and grey matter (NAGM) volumes from superior, middle and inferior frontal lobe were compared between DTC quartiles (adjusted for age, sex, and education) using a multivariate model (MANOVA), with total frontal lobe volume as a covariate. Another model compared group performance across 5 adjusted cognitive domains (attention, memory, language, visuospatial performance, and executive functioning). Univariate tests revealed that NAWM volume in the superior frontal lobe (F=4.50; p=0.005; partial eta-squared=0.122) was significantly different across DTC quartiles. Contrast tests suggested that the first quartile had larger NAWM than the second and fourth. DTC quartiles also showed differences in attention (F=2.93; p=0.03; partial eta-squared=0.083) and contrast tests indicated that the first quartile performed significantly better than second and fourth. DTC poststroke may be a proxy for structural integrity of superior frontal lobe regions and attention.

The Impact of Sleep Disturbance on Regional Brain Volumes

Sleep disruption has been associated with increased beta-amyloid deposition and greater risk for later development of Alzheimer’s disease. Studies indicate that sleep disturbance correlates with regional brain volumes, but data are limited. We sought to determine the effect of sleep disturbance on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status. We conducted a secondary analysis of the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set using complete structural imaging data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of sleep disturbance (via Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Sleep disruption was associated with greater volumes in the right and left lateral ventricles and greater volume of total white matter hyperintensities (p<.05). Lower mean volumes in total brain, total gray matter, and total cerebrum grey matter volumes, and in 12 hippocampal, frontal, parietal, and temporal lobe volumes were observed among participants who reported sleep disturbance. Males, Hispanic participants, and those with less education were more likely to report sleep disruption. Cognitive status moderated the relationship between sleep disturbance and lateral ventricular volumes, while APOE e4 moderated the effect between sleep disturbance and parietal lobe volumes. These findings suggest that disrupted sleep is associated with atrophy across multiple brain regions and ventricular hydrocephalus ex vacuo, after controlling for intracranial volume and demographic covariates. The influence of cognition and APOE e4 status indicates that this relationship is affected by co-occurring physiological processes.

The Effect of Anxiety on Regional Brain Volumes in the National Alzheimer’s Coordinating Center Uniform Data Set

Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk.

Trajectory of apathy, cognition and neural correlates in the decades before symptoms in frontotemporal dementia

AbstractBackgroundIn frontotemporal dementia (FTD), apathy is reported to negatively impact the prognosis and survival of patients. The study of genetic FTD in its pre‐symptomatic period permits the investigation of markers in the early stages of disease progression. Therefore, in pre‐symptomatic gene carriers in the multicentre Genetic FTD Initiative (GENFI), we examined longitudinal apathy changes in association with cognitive decline over time, and baseline measures of atrophy.MethodSix hundred participants from Data Freeze 4 (2019) were included: 304 pre‐symptomatic mutation carriers, and 296 family members without mutations. Clinical assessment and a structural MRI scan were undertaken at baseline, and annually for at least 2‐years. Latent Growth Curve modelling (LGCM) was used to assess: 1) longitudinal changes in apathy, as measured by the apathy subscale of the Revised Cambridge Behavioural Inventory; 2) the relationship with longitudinal changes in executive function; 3) the association with baseline regional grey matter volumes. The time to the expected year of symptom onset was included as a covariate.ResultUnivariate LGCM identified a significant linear increase in apathy scores for pre‐symptomatic carriers (estimate= 0.51, se=0.18, z scores= 2.88, p=0.004), but not in non‐carriers (estimate= 0.08, se=0.08, z scores=1.04, p=0.30). An equality constrained comparison suggested a significant group difference in the progression of apathy (i.e. the slope) ((∆ χ2=10.14; p=0.0015). Pre‐symptomatic carriers also had a significant decline in executive functions (est=‐0.07, se=0.03, z scores=‐2.49, p=0.017), which was predicted by baseline apathy (standard estimate=‐0.40, p=0.008). In pre‐symptomatic carriers only, the annual rate of change in apathy was significantly associated with brain volume in frontal lobe (standard estimate=‐0.47, p=0.008) and cingulate cortex (standard estimate=‐0.29, p=0.05) at the baseline.ConclusionApathy progresses significantly in pre‐symptomatic FTD and predicts a sub‐clinical deterioration of executive performance in gene carriers. Apathy changes over 2 years are associated with volume in the frontal lobe and cingulate gyrus measured at the baseline. We suggest that apathy may be a modifiable factor to protect function and cognition in those with, or at risk of, frontotemporal dementia.

Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment.

Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n = 326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T1 and white matter hyperintensities assessed on T2-FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p = 0.01), frontal lobe (p = 0.01), and occipital lobe volumes (p = 0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p = 0.005) and hippocampal volume (p = 0.05). Subtle age-related cardiac changes may disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.

Association of SBP and BMI with cognitive and structural brain phenotypes in UK Biobank.

To test for associations between SBP and BMI, with domain-specific cognitive abilities and examine which brain structural phenotypes mediate those associations. Using cross-sectional UK Biobank data (final N = 28 412), we examined SBP/BMI vs. cognitive test scores of pairs-matching, matrix completion, trail making test A/B, digit symbol substitution, verbal-numerical reasoning, tower rearranging and simple reaction time. We adjusted for potential confounders of age, sex, deprivation, medication, apolipoprotein e4 genotype, smoking, population stratification and genotypic array. We tested for mediation via multiple structural brain imaging phenotypes and corrected for multiple testing with false discovery rate. We found positive associations for higher BMI with worse reaction time, reasoning, tower rearranging and matrix completion tasks by 0.024-0.067 SDs per BMI SD (all P < 0.001). Higher SBP was associated with worse reasoning (0.034 SDs) and matrix completion scores (-0.024 SDs; both P < 0.001). Both BMI and SBP were associated with multiple brain structural metrics including total grey/white matter volumes, frontal lobe volumes, white matter tract integrity and white matter hyperintensity volumes: specific metrics mediated around one-third of the associations with cognition. Our findings add to the body of evidence that addressing cardiovascular risk factors may also preserve cognitive function, via specific aspects of brain structure.

Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects

BackgroundChildhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AimTo study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. MethodIn seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. ResultsOf the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. ConclusionsChildhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

Body mass index, residual psychotic symptoms, and inflammation associated with brain volume reduction in older patients with schizophrenia.

Clinically stable outpatients with schizophrenia (DSM-IV) aged ≥50 years were recruited to undergo whole-brain magnetic resonance imaging. We measured patients' plasma levels of soluble tumor necrosis factor receptor-1, soluble interleukin (IL)-2 receptor (sIL-2R), IL-1β, and IL-1 receptor antagonist (IL-1Ra). Clinical data were obtained from medical records and interviewing patients along with their reliable others. There were 32 patients with mean age 58.8 years in this study. Multivariate regression analysis found only higher BMI significantly associated with lower volume of total gray matter, bilateral orbitofrontal and prefrontal cortexes, and the right hippocampal and frontal cortexes. Increased intensity of residual symptoms (higher Positive and Negative Syndrome Scale scores) was related to lower volumes of frontal lobe, prefrontal cortex, insula, hippocampus, left hemisphere amygdala, and total white matter. The lower volume of left anterior cingulum was associated with older age and higher sIL-2R plasma level; and higher IL-1Ra level was associated with greater right anterior cingulate volume. Older age at illness onset was significantly associated with the smaller right insula volume. Higher BMI, more residual symptoms, and inflammatory activity in IL-2 and IL-1 systems may play a role in gray matter loss in various brain regions of schizophrenia across the life span.