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Neurosurgical Focus Aug 2018Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed... (Review)
Review
Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
Topics: Animals; Brain Injuries, Traumatic; Cognition; Consciousness; Deep Brain Stimulation; Epilepsy; Humans; Thalamus
PubMed: 30064315
DOI: 10.3171/2018.5.FOCUS18168 -
Aging Cell Jul 2023Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's... (Observational Study)
Observational Study
Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10 ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.
Topics: Humans; Alzheimer Disease; Mendelian Randomization Analysis; Biological Specimen Banks; Leukocytes; Telomere; United Kingdom
PubMed: 37254630
DOI: 10.1111/acel.13808 -
Cellular and Molecular Life Sciences :... Sep 2020Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and... (Review)
Review
Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and obsessive-compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer's disease (n = 9), traumatic brain injury (n = 2), Rett syndrome (n = 1), and temporal lobe epilepsy (n = 1). Overall, fornix stimulation can lead to decreased rates of cognitive decline (in humans), enhanced memory (in humans and animals), visuo-spatial memorization (in humans and animals), and improving verbal recollection (in humans). While the exact mechanisms of action are not completely understood, studies suggest fornix DBS to be involved with increased functional connectivity and neurotransmitter levels, as well as enhanced neuroplasticity.
Topics: Alzheimer Disease; Animals; Brain Injuries, Traumatic; Deep Brain Stimulation; Epilepsy; Fornix, Brain; Humans; Memory; Memory Disorders; Rett Syndrome
PubMed: 31974655
DOI: 10.1007/s00018-020-03456-4 -
Neurobiology of Learning and Memory Oct 2020Many neurological patients suffer from memory loss. To date, pharmacological treatments for memory disorders have limited and short-lasting effects. Therefore,... (Review)
Review
Many neurological patients suffer from memory loss. To date, pharmacological treatments for memory disorders have limited and short-lasting effects. Therefore, researchers are investigating novel therapies such as deep brain stimulation (DBS) to alleviate memory impairments. Up to now stimulation of the fornix, nucleus basalis of Meynert and entorhinal cortex have been found to enhance memory performance. Here, we provide an overview of the different DBS targets and mechanisms within the memory circuit, which could be relevant for enhancing memory in patients. Future studies are warranted, accelerating the efforts to further unravel mechanisms of action of DBS in memory-related disorders and develop stimulation protocols based on these mechanisms.
Topics: Alzheimer Disease; Animals; Basal Nucleus of Meynert; Brain; Cognition; Deep Brain Stimulation; Entorhinal Cortex; Fornix, Brain; Humans; Memory; Translational Research, Biomedical
PubMed: 32739395
DOI: 10.1016/j.nlm.2020.107283 -
Brain and Neuroscience Advances 2020The fornix is a key tract of the hippocampal formation, whose status is presumed to contribute to age-related cognitive decline. The precommissural and postcommissural...
The fornix is a key tract of the hippocampal formation, whose status is presumed to contribute to age-related cognitive decline. The precommissural and postcommissural fornix subdivisions form respective basal forebrain/frontal and diencephalic networks that may differentially affect aging and cognition. We employed multi-parametric magnetic resonance imaging (MRI) including neurite orientation density and dispersion imaging, quantitative magnetization transfer (qMT), and T-relaxometry MRI to investigate the microstructural properties of these fornix subdivisions and their relationship with aging and cognition in 149 asymptomatic participants (38-71 years). Aging was associated with increased free water signal and reductions in myelin-sensitive R and qMT indices but no apparent axon density differences in both precommissural and postcommissural fibers. Precommissural relative to postcommissural fibers showed a distinct microstructural pattern characterised by larger free water signal and axon orientation dispersion, with lower apparent myelin and axon density. Furthermore, differences in postcommissural microstructure were related to performance differences in object-location paired-associate learning. These results provide novel in vivo neuroimaging evidence for distinct microstructural properties of precommissural and postcommissural fibers that are consistent with their anatomy as found in axonal tracer studies, as well as for a contribution of postcommissural fibers to the learning of spatial configurations.
PubMed: 32219177
DOI: 10.1177/2398212819899316