Alzheimer's research & therapy
-
Alzheimers Res Ther · Jan 2014
ReviewImaging as a biomarker in drug discovery for Alzheimer's disease: is MRI a suitable technology?
This review provides perspectives on the utility of magnetic resonance imaging (MRI) as a neuroimaging approach in the development of novel treatments for Alzheimer's disease. These considerations were generated in a roundtable at a recent Wellcome Trust meeting that included experts from academia and industry. It was agreed that MRI, either structural or functional, could be used as a diagnostic, for assessing worsening of disease status, for monitoring vascular pathology, and for stratifying clinical trial populations. It was agreed also that MRI implementation is in its infancy, requiring more evidence of association with the disease states, test-retest data, better standardization across multiple clinical sites, and application in multimodal approaches which include other imaging technologies, such as positron emission tomography, electroencephalography, and magnetoencephalography.
-
Alzheimers Res Ther · Jan 2014
ReviewChronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel.
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive traumatic brain injury experienced in sport and military service. In most instances, the clinical symptoms of the disease begin after a long period of latency ranging from several years to several decades. The initial symptoms are typically insidious, consisting of irritability, impulsivity, aggression, depression, short-term memory loss and heightened suicidality. ⋯ As CTE is characterized pathologically by frontal and temporal lobe atrophy, by abnormal deposits of phosphorylated tau and by 43 kDa TAR DNA binding protein and is associated clinically with behavioral and personality changes, as well as cognitive impairments, CTE is increasingly categorized as an acquired frontotemporal lobar degeneration. Currently, some of the greatest challenges are that CTE cannot be diagnosed during life and the incidence and prevalence of the disorder remain uncertain. Furthermore, the contribution of age, gender, genetics, stress, alcohol and substance abuse to the development of CTE remains to be determined.
-
Alzheimers Res Ther · Jan 2014
ReviewClinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome.
The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. ⋯ These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders.
-
Since the launch in 2003 of the Alzheimer's Disease Neuroimaging Initiative (ADNI) in the USA, ever growing, similarly oriented consortia have been organized and assembled around the world. The various accomplishments of ADNI have contributed substantially to a better understanding of the underlying physiopathology of aging and Alzheimer's disease (AD). ⋯ This multimodality approach can now better identify those subjects with AD-specific traits that are more likely to present cognitive decline in the near future and that might represent the best candidates for smaller but more efficient therapeutic trials - trials that, through gained and shared knowledge, can be more focused on a specific target or a specific stage of the disease process. In summary, data generated from ADNI have helped elucidate some of the pathophysiological mechanisms underpinning aging and AD pathology, while contributing to the international effort in setting the groundwork for biomarker discovery and establishing standards for early diagnosis of AD.
-
Alzheimers Res Ther · Jan 2014
ReviewConsiderations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.
The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. ⋯ The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath.