Alzheimer′s disease: The role for neurosurgery

Abstract

Dementia, most commonly caused by Alzheimer's disease (AD), affects approximately 35 million people worldwide, with the incidence expected to increase as the population ages. After decades of investigation, AD is now understood to be a complex disease that affects behavior and cognition through several mechanisms: Disrupted neuronal communication, abnormal regional tissue metabolism, and impaired cellular repair. Existing therapies have demonstrated limited efficacy, which has spurred the search for specific disease markers and predictors as well as innovative therapeutic options. Deep brain stimulation (DBS) of the memory circuits is one such option, with early studies suggesting that modulation of neural activity in these networks may improve cognitive function. Encapsulated cell biodelivery (ECB) is a device that delivers nerve growth factor to the cholinergic basal forebrain to potentially improve cognitive decline in AD patients. This review discusses the pathogenesis of AD, novel neuroimaging and biochemical markers, and the emerging role for neurosurgical applications such as DBS and ECB.

Deep Brain Stimulation for Alzheimer's Disease

“…Several animal studies have shown that delivery of nerve growth factor (NFG) -a member of neurotrophin family that plays a role in cholinergic synaptic remodeling in the adult CNS-in basal forebrain (anterior part of the brain, cerebral hemispheres, thalamus and hypothalamus) by encapsulated cell biodelivery (ECB) could arrest or even reverse the neuronal degeneration process [31,32]. In 2012 Wahlberg et al, evaluated the safety and the clinical efficacy of ECB for use in humans [32].…”

“…These molecular alterations lead to neuronal loss and cerebral atrophy in different regions of the brain involving frontal, temporal, parietal, hippocampus and entorhinal cortex (EC). AD also disrupts the neuronal connections between the cortical and subcortical areas [4,7,9].…”

“…The application of DBS in neurodegenerative and neuropsychological conditions such as Parkinson's disease, obsessive compulsive disorder and major depression is nearly demonstrated [6,7]. In the etiopathogenesis of AD accumulations of abnormal proteins (beta amyloid and tau protein), inflammatory cascades, abnormal responses to oxidative stress and alteration in oxidative metabolism are implicated [4,[8][9][10]. At molecular level, these proteins are responsible of the loss of synaptic functions, defective metabolism, impaired cellular repair and cell death.…”

Effects and mechanism of lipoic acid on beta-amyloid-intoxicated C6 glioma cells

“…AD presents a difficult medical problem across many clinical disciplines including neurology and gerontology (Willhite et al, 2014). Its pathological changes primarily consist of brain tissue atrophy with a large amount of β-amyloid peptide (Aβ) deposition in the brain tissue and brain blood vessels, and the presence of senile plaques and neurofibrillary tangles in hippocampal neurons (Pereira et al, 2014) Studies have shown that multiple factors including the destruction of calcium homeostasis, apolipoprotein E, free radical damage, metabolic disorders, and cholinergic injury might induce AD (Arevalo-Rodriguez et al, 2014;Bazin and Bratu, 2014;Savioz et al, 2014). However, the pathogenesis of AD has not been fully elucidated.…”

Neuromodulation for restoring memory

“…62 In AD there is decreased activity in the precuneus and posterior cingulate, which comprise the posterior default mode network, with decreased connectivity in all areas as the disease progresses. 83 …”