Guide Biology of Brain Dysfunction: Volume 1

Free download. Book file PDF easily for everyone and every device. You can download and read online Biology of Brain Dysfunction: Volume 1 file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Biology of Brain Dysfunction: Volume 1 book. Happy reading Biology of Brain Dysfunction: Volume 1 Bookeveryone. Download file Free Book PDF Biology of Brain Dysfunction: Volume 1 at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The CompletePDF Book Library. It's free to register here to get Book file PDF Biology of Brain Dysfunction: Volume 1 Pocket Guide.

Illustration Credit: Ben Smith. In summary, experimental studies and human data indicate that oxidative stress and inflammation are critical factors in the alterations in neurovascular and endothelial function produced by hypertension. Furthermore, innate immune cells, the PVM in particular, have emerged as a powerful source of vascular ROS production. The alterations in cerebrovascular structure and function induced by hypertension described in the previous sections predispose the brain to dysfunction and damage, which, in turn, alters cognition.

Chronic hypertension is the major risk factor for ischemic and hemorrhagic stroke, which is associated with a 3- to 6-fold increase in cognitive impairment, especially when multiple strokes are involved multi-infarct dementia. The most common brain lesions associated with hypertension are white matter lesions, especially in the frontal cortex, which appear as areas of hyperintensity on T2-weighted MRI. A population of oligodendrocytes associated specifically with cerebral blood vessels has been identified and oligodendrocyte proliferation and survival requires vascular growth factors.

Indeed, arrested development of oligodendrocyte precursors has been observed human white matter in SVD resulting in faulty remyelination of damaged white matter Figure 4. Figure 4. Potential mechanisms of white matter WM damage by hypertension. Vascular oxidative stress and inflammation disrupt the blood-brain barrier BBB , induce neurovascular unit NVU dysfunction and damage, and impair oligodendrocyte development and function.

The resulting alterations in tissue homeostasis, hypoxia-ischemia, reduced brain clearance, and impaired remyelination lead to WM damage. In summary, oxidative stress, hypoxia-ischemia, inflammation, and BBB dysfunction are critical vascular factors threatening the health of the subcortical white matter. There might be regional differences on the impact of hypertension on white matter, and the white matter of the frontal lobe may be more susceptible. Atrophy, brain damage caused by macroinfarcts and microinfarcts, and hemorrhages are important determinants of cognitive impairment.

Furthermore, infarcts strategically placed in brain regions involved in cognition, for example, hippocampus, medial thalamus, and frontal lobe, can produce cognitive dysfunction, despite relatively small volume of damage, 66 , and the estimated functional impact of microinfarcts is greater than anticipated by the volume of injury. The impact of enlarged perivascular spaces on cognitive impairment of hypertension remains uncertain. The morphological alterations of the perivascular space raise the possibility that perivascular and paravascular clearance systems may be altered and have a role in the white matter damage.

Therefore, direct evidence linking hypertension to brain clearance pathways has not been provided, in humans as in animal models, and additional work is needed in this area. These observations, collectively, suggest that hypertension may lead to cognitive impairment through several pathogenic factors Figure 5. Gray matter loss, loss of connectivity and network efficiency from white matter lesions, reduced perivascular clearance, and neurovascular dysfunction all have the potential to impair brain function, but their relative impact on cognitive processes remain to be established.

Figure 5. Brain lesions produced by hypertension that underlie cognitive impairment. Brain atrophy, microinfarcts, and microbleeds cause neuronal loss and brain dysfunction. In addition, microinfarcts and microbleeds disrupt brain connectivity and reduce network efficiency. Damage to white matter lesions WML also degrades connectivity, especially in thalamo-cortico networks. Alteration in perivascular spaces PVS impairs brain clearance and may promote protein accumulation in brain and vessels, and dysfunction of the neurovascular unit NVU leads to vascular insufficiency and BBB damage.

Potential interactions between different pathogenic mechanisms are indicated by the dashed arrows. CBF indicates cerebral blood flow. A large body of evidence indicates that hypertension is a risk factor for AD—a condition once considered purely a neurodegenerative disease. In the ARIC-PET study, nondemented participants with a greater number of vascular risk factors in middle age, including hypertension, had more elevated brain amyloid in late life, suggesting a possible direct impact of these risk factors on amyloid; hypertension by itself, however, was not significantly associated with elevated amyloid so may not have an independent role.

In addition to the above-cited studies of elevated BP and brain atrophy, 42 midlife BP has also been associated with hippocampal atrophy by MRI, with the strongest associations among untreated hypertensives. At the same time, administration of renin-angiotensin system blockers or AT1R genetic deletion ameliorates amyloid deposition and behavioral dysfunction in APP-overexpressing mice. Endothelial NO prevents tau phosphorylation by inhibiting Cdk5 cyclin-dependent kinase-5 —one of the main kinases phosphorylating tau —and consequently the NO deficit associated with hypertension could promote tau phosphorylation.

Figure 6. Potential mechanisms underlying the relationship between hypertension and Alzheimer disease AD.

Related Stories

BBB indicates blood-brain barrier. Adapted from Iadecola et al 8 with permission. These clinical and experimental observations, collectively, suggest that hypertension has the potential to promote AD pathology by acting at different levels. However, it remains unclear whether hypertension is a pathogenic factor in AD, and, conversely, whether the AD pathology associated with hypertension is a contributor to the cognitive dysfunction. Given the strong and consistent associations seen in the epidemiological literature between hypertension and dementia, and given the strong biological plausibility for a link between the two, the inevitable next question is whether treatment of hypertension reduces risk of dementia.

Certainly, this is the major reason why the study of hypertension as a risk factor for dementia is of particular interest: in the absence of other ways to treat or prevent dementia and AD specifically, hypertension is an especially appealing target. Several epidemiological studies have considered the role of antihypertensive medication treatment, although all remain susceptible to some indication bias: individuals who are prescribed and take antihypertensives are different than people who do not, in many ways beyond which can be adjusted statistically.

Thus, clinical trials would be the ideal forum in which to test this question, but given the above reviewed evidence that relationships between hypertension and dementia are the strongest when hypertension is considered in middle age, decades before the development of dementia, and that clinical trials cannot randomize and follow participants for that long duration, some reliance on longer term observational study designs is needed to consider these life span considerations.

These studies also allow consideration of age of treatment or duration of treatment, which can extend beyond the windows allowed by clinical trials. In several observational studies, antihypertensive medication use is associated with less cognitive decline; in the ARIC study, participants taking antihypertensive medications had a year cognitive decline equivalent to a prehypertensive group higher than the normotensives but lower than untreated hypertensives.

In the HAAS study, per additional year of antihypertensive treatment, dementia risk was lower hazard ratio, 0. Although the focus of this review is on hypertension, elevated BP as a risk factor rarely occurs in isolation, and several risk factors co-occurring in the same individuals may further increase accelerated cognitive decline. In the Framingham Heart Study, hypertension was associated with worse decline in the presence of diabetes mellitus compared with its effect in nondiabetics, and in the Framingham Offspring Study, cognitive outcomes were the worst among participants with hypertension and elevated waist-hip ratio.

Similar relationships are seen when consideration is made of any additional risk factor: in participants of the Kaiser HMO Health Maintenance Organization , an increasing number of midlife vascular risk factors was associated with elevated risk of dementia in late life, with a hazard ratio of 1.

A growing body of evidence supports the biological importance of the renin-angiotensin system and points to the potential importance of drugs within this family for dementia prevention in individuals with hypertension. Intervention trials in SHR have shown reduced poststroke cognitive impairment in rodents treated with renin-angiotensin system modifiers specifically candesartan—an AT1R blocker. The optimal treatment regimen to prevent future cognitive impairment or dementia is difficult to ascertain because nearly all antihypertensives have studies supporting their potential benefit.

Again, these are still likely confounded by indication bias, similar to the overall issue of indication bias regarding any antihypertensive use versus none, although to a lesser degree considering one antihypertensive versus another may be influenced by comorbidities or demographic characteristics but are less profoundly impacted by socioeconomic or other factors influencing access to medical care more broadly. Although the body of knowledge relating hypertension to cognitive outcomes, dementia, and AD has expanded tremendously in recent years, several key questions remain.

Answers to some of these questions, listed below, will be critical to gain a better insight into how hypertension impacts cognitive function and to best recommend prevention and management strategies. Hypertension induces alterations in neurovascular function, which are thought to induce brain lesions associated with cognitive impairment Figure 5.

However, it remains to be established whether the neurovascular dysfunction alone is sufficient to induced cognitive impairment. Reduced cerebral perfusion, alterations in brain clearance and BBB, as well as vascular growth factor deficiency have the potential to alter neuronal function in metabolically active brain regions involved in cognitive function, such as the hippocampus, entorinal cortex, and prefrontal cortex.

A better understanding of the natural history of the impact of hypertension on cerebrovascular function, network degradation, and cognition would be needed to address this question, which is relevant to the initiation of antihypertensive therapy. In parallel, a more nuanced understanding of the signaling mechanisms by which the neurovascular dysfunction interferes with neuronal function would also be desirable.

Is CBF insufficiency the major factor? Or, are there other aspects of cerebrovascular biology, such as trophic support by endothelial factors or perivascular clearance, also at play? As summarized above, the benefits of antihypertensive therapy are likely to be the greatest when initiated in midlife, and continued over decades, although preliminary results from the SPRINT-MIND trial suggest that benefits may still be possible with a shorter duration of antihypertensive therapy.

Biosocial Theory

In this regard, it would be important to assess whether the appearance of brain lesions diminishes the impact of hypertensive therapy on cognitive health. Although difficult to study in clinical trials, further consideration will need to be made of optimal age and duration of antihypertensive therapy, and correlation with cardiovascular and structural-functional imaging biomarkers, to best prevent cognitive decline, MCI, and dementia. Individuals with more vascular risk factors appear especially vulnerable to hypertension, with worse outcomes among individuals with several vascular risk factors.

This suggests that individuals with other known risk factors, such as diabetes mellitus, may need better screening of BP with a lower threshold for initiation of antihypertensive therapy. This is consistent with the management of vascular risk factors because they relate to other cardiovascular outcomes.

Beyond vascular risk, there may be genetic susceptibilities, such as has been seen with the APOE data, leading to greater risk and, therefore, greater potential benefit from antihypertensive therapy, in individuals with a known risk allele or even of a particular race or sex. Focused trials with enrollment of these higher risk groups could identify a subgroup in whom prevention might be especially effective.

Although ongoing studies are directly addressing the potential benefit of particular antihypertensives, at least on surrogate end points, at the time of this manuscript preparation, no convincing data point to a clinical difference with the use of particular antihypertensive medications. This question—whether any antihypertensive is as effective as the next—will be critical as evidence is translated into practice.

Furthermore, it is possible that the same recommended therapeutics may not be ideal for all individuals. Race-based differences in therapeutic effect for distinct antihypertensives have been noted for other cardiovascular outcomes, and similar differences by race, or other demographic or genetic factors, may be found for reduction of adverse cognitive outcomes. Biomarkers or surrogate end points are valuable in studying long-term relationships as seen between hypertension and dementia because they allow for earlier assessment of therapeutic effect, both for research purposes, as well as clinically, to evaluate benefits of treatment.

Ongoing studies and consortia, including MarkVCID Mark Vascular Contributions to Cognitive Impairment and Dementia , are evaluating biomarkers for the vascular contribution to cognitive impairment and dementia, which likely would be candidates for the specific effect of hypertension on the brain as well, and may include serum, CSF, or imaging markers to examine the contribution from AD pathology.

As discussed in a previous section, there is biological plausibility that hypertension and other vascular risk factors may promote AD pathology and vice versa. However, the clinical-pathological evidence remains contradictory. The recent development and validation of amyloid and tau PET imaging provides the opportunity to examine in vivo the reciprocal interaction between markers of AD and hypertensive neuropathology and their relative contribution to cognitive impairment.

These findings would have important implications for targeting treatments to the relevant pathology responsible for the cognitive deficits in a particular individual. These are a few of the outstanding questions that remain to be addressed. Answering these questions will require engaging both the preclinical and clinical scientific communities in a concerted effort to advance the understanding of how hypertension affects brain function leading to cognitive impairment.

Thus, epidemiological, biomarker, and clinical-pathological studies should be closely related to basic science efforts to unravel mechanisms and provide new targets to be tested in clinical trials. Such cooperation will be essential for the development of new diagnostic tools and treatment strategies for one of the most devastating health challenges of our times.

Iadecola , RNS C. Iadecola , KAG R. Gottesman , and RAG R. Gottesman is Associate Editor for the journal Neurology. Home Circulation Research Vol. View PDF. Tools Add to favorites Download citations Track citations Permissions. Jump to. Rebecca F. Gottesman Rebecca F. Gottesman Departments of Neurology R. Epidemiology R. Abstract Hypertension has emerged as a leading cause of age-related cognitive impairment. Download figure Download PowerPoint. Email coi med. References 1. Global burden of hypertension and systolic blood pressure of at least to mm Hg, Spieth W. Cardiovascular health status, age, and psychological performance.

J Gerontol. Crossref Medline Google Scholar 4. Wilkie F, Eisdorfer C. Intelligence and blood pressure in the aged. Crossref Medline Google Scholar 5. The blood flow, vascular resistance, and oxygen consumption of the brain in essential hypertension. J Clin Invest.

Brain differences in ADHD

Crossref Google Scholar 6. Timeline of history of hypertension treatment. Front Cardiovasc Med. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol. Crossref Medline Google Scholar 8. Iadecola C, Gottesman RF. Cerebrovascular alterations in alzheimer disease. Circ Res. Moser M, Roccella EJ. The treatment of hypertension: a remarkable success story. J Clin Hypertens Greenwich. Impact of hypertension on cognitive function: a scientific statement from the American Heart Association.

Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study. Midlife hypertension and year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol.

Association of midlife blood pressure to late-life cognitive decline and brain morphology. Crossref Medline Google Scholar The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study. Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study.

Midlife cardiovascular risk factors and risk of dementia in late life. F2 Crossref Medline Google Scholar Midlife pulse pressure and incidence of dementia: the Honolulu-Asia Aging Study. Associations between midlife vascular risk factors and year incident dementia in the atherosclerosis risk in communities ARIC cohort.

High blood pressure and cognitive decline in mild cognitive impairment. J Am Geriatr Soc. Alzheimer Dis Assoc Disord. Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline. Hypertension is related to cognitive impairment: a year follow-up of men. Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study.

Current and remote blood pressure and cognitive decline. Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H Study. Dement Geriatr Cogn Disord. Low blood pressure and the risk of dementia in very old individuals. Nonlinear relations of blood pressure to cognitive function: the Baltimore Longitudinal Study of Aging.

Midlife and late-life blood pressure and dementia in Japanese elderly: the Hisayama study. Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Change in blood pressure and incident dementia: a year prospective study. Blood pressure from mid- to late life and risk of incident dementia. Low blood pressure and incidence of dementia in a very old sample: dependent on initial cognition.

Crossref Google Scholar Association between blood pressure levels over time and brain atrophy in the elderly. Neurobiol Aging. Life-course blood pressure in relation to brain volumes. Alzheimers Dement. Early adult to midlife cardiovascular risk factors and cognitive function. Associations between potentially modifiable risk factors and Alzheimer disease: a mendelian randomization study. PLoS Med. The relationship between cognitive functioning and the JNC-8 guidelines for hypertension in older adults.

Frith, C. The social brain?

Recommended for you

B Biol. Frith, U. Mind blindness and the brain in autism. Neuron 32, — Development and neurophysiology of mentalizing. Gebauer, L. Is there a bit of autism in all of us? Autism spectrum traits are related to cortical thickness differences in both autism and typical development. Autism Spectr. Grelotti, D. Social interest and the development of cortical face specialization: what autism teaches us about face processing. Hadjikhani, N. Anatomical differences in the mirror neuron system and social cognition network in autism. Cortex 16, — Hall, G. Haxby, J. The distributed human neural system for face perception.

Hayasaka, S. Nonstationary cluster-size inference with random field and permutation methods. Neuroimage 22, — Hobson, P. The Cradle of Thought. London: Macmillan, Hoffmann, E. Reduced functional connectivity to the frontal cortex during processing of social cues in autism spectrum disorder. Neural Transm.

Biology of obsessive–compulsive disorder - Wikipedia

Itahashi, T. Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: a multimodal brain imaging study. Neuroimage Clin. Johnson, M. The emergence of the social brain network: evidence from typical and atypical development.

Kaiser, M. Neural signatures of autism. Kana, R. Atypical frontal-posterior synchronization of Theory of Mind regions in autism during mental state attribution. Kleinhans, N. Abnormal functional connectivity in autism spectrum disorders during face processing. Koshino, H. Cortex 18, — Koyama, T. Psychiatry Clin. Kreifelts, B. Non-verbal emotion communication training induces specific changes in brain function and structure.

Krishnan, A. Neuroimage 56, — Kwon, H. Voxel-based morphometry elucidates structural neuroanatomy of high-functioning autism and Asperger syndrome. Child Neurol. Lai, M. Neuroanatomy of individual differences in language in adult males with autism. Cortex 25, — Biological sex affects the neurobiology of autism. Libero, L. Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates.

Cortex 66, 46— Lynn, A. Functional connectivity differences in autism during face and car recognition: underconnectivity and atypical age-related changes. Magyar, C. Factor structure evaluation of the childhood autism rating scale. Adaptive non-local means denoising of MR images with spatially varying noise levels. Imaging 31, — McAlonan, G. Psychiatry 49, — McIntosh, A. Spatial pattern analysis of functional brain images using partial least squares.

Neuroimage 3, — Partial least squares analysis of neuroimaging data: applications and advances. Neuroimage 23, — Mesibov, G. Use of the childhood autism rating scale with autistic adolescents and adults. Child Adolesc. Psychiatry 28, — Mody, M. Speech and language impairments in autism: insights from behavior and neuroimaging. Mueller, S. Convergent findings of altered functional and structural brain connectivity in individuals with high functioning autism: a multimodal MRI study.

Nickl-Jockschat, T.


  1. Login to your account;
  2. Neuroscience Related Articles?
  3. The Routledge Introductory Persian Course: Farsi Shirin Ast.
  4. Crafting Creativity & Creating Craft: Craftivism, Art Education, and Contemporary Craft Culture;

Brain structure anomalies in autism spectrum disorder—a meta-analysis of VBM studies using anatomic likelihood estimation. Brain Mapp. Neural networks related to dysfunctional face processing in autism spectrum disorder. Brain Struct. Pelphrey, K. Charting the typical and atypical development of the social brain. Neural basis of eye gaze processing deficits in autism. Philip, R.

A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders. Pierce, K. The brain response to personally familiar faces in autism: findings of fusiform activity and beyond. Rajapakse, J. Statistical approach to segmentation of single-channel cerebral MR images. IEEE Trans. Imaging 16, — Riedel, A. No significant brain volume decreases or increases in adults with high-functioning autism spectrum disorder and above average intelligence: a voxel-based morphometric study. Psychiatry Res. Rizzolatti, G. Neurophysiological mechanisms underlying the understanding and imitation of action.

Rolls, E. The functions of the orbitofrontal cortex. Brain Cogn. Rudebeck, P. Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values. Sacco, R. Head circumference and brain size in autism spectrum disorder: a systematic review and meta-analysis. Sato, W. Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders. BMC Neurosci.

Scheel, C. Imaging derived cortical thickness reduction in high-functioning autism: key regions and temporal slope. Neuroimage 58, — Scherf, K. Location, location, location: alterations in the functional topography of face- but not object- or place-related cortex in adolescents with autism. Schmitz, N. Neural correlates of executive function in autistic spectrum disorders. Psychiatry 59, 7— Neural correlates of reward in autism. Psychiatry , 19— Schopler, E. New York, NY: Irvington, Schultz, R.

Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome. Psychiatry 57, — Sharda, M. Language ability predicts cortical structure and covariance in boys with autism spectrum disorder. Cortex 27, — Sheehan, D. Psychiatry 59, 22— PubMed Abstract Google Scholar. Smith, S. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44, 83— Sturm, V. DBS in the basolateral amygdala improves symptoms of autism and related self-injurious behavior: a case report and hypothesis on the pathogenesis of the disorder.

Toal, F. Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study. Tohka, J. Fast and robust parameter estimation for statistical partial volume models in brain MRI. Neuroimage 23, 84— Trepagnier, C. Atypical face gaze in autism. The inverse relationship was also observed. The causes of the differences in gray matter volume are unknown, but IED runs in families and is thought to have a significant genetic component. Developmental processes and environmental influences may also play a role, and further studies are needed to investigate.

UChicago Medicine offers primary and specialty care at over 40 locations throughout Illinois and Indiana. UChicago Medicine and Ingalls Memorial offer a broad range of challenging clinical and non-clinical career opportunities doing work that really matters. Close MyChart MyChart is not for medical emergencies. If you have a medical emergency, call If you need help with MyChart, call us at Share with facebook Share with twitter Share with linkedin. Forefront Neuroscience.

Individuals with rage disorder have smaller volumes in brain areas linked to emotion. Call Us At Additional authors include Daniel A.