Neurological Disorders Flashcards

Question

What is Parkinson's Disease

Answer 1

degeneration of nigrostriatal system dopamine-secreting neurons of substantia nigra send axons to basal ganglia and striatum seen in 1% of 65+ year olds

Answer 2

muscular rigidity slowness of movement resting tremor = vibratory movements of arms and hands that diminish when purposeful movements made

Answer 3

functional-imaging studies show near-disappearance of nigrostriatal dopaminergic neurons - effect of this shows: akinesia (difficulty in initiating movements) is associated with decreased activation of supplementary motor area and tremors are associated with abnormalities of neural system including pons, midbrain, cerebellum and thalamus

Answer 4

decreased release of dopamine into caudate nucleus and putamen this causes increase in globus pallidus activity output of globus pallidus through VA/VL thalamus to motor cortex is inhibitory more activity of globus pallidus makes it difficult for motor cortex to initiate movement

Answer 5

abnormal circular structures found in cytoplasm consists of aggregations of misfolded proteins, abnormal alpha-synuclein, neurofilaments and synaptic vesicle proteins

Answer 6

proteasomes destroy misfolded protein into its amino acids parkin, a gene on chromosome 6 ferries misfolded proteins to proteasomes after attaching molecules of ubiquitin mutation of chromosome 6 gene causes accumulation of misfolded proteins in dopamine cells, destroying cells 95% parkinson patients have no family history - toxins like insectides are associated with parkinson's by disrupting mitochondrial functions proteasomal and mitochondrial functioning are closely linked

Answer 7

nigrostriatal system - this is damaged by Parkinson's disease - involved in movement mesolimbic system (innervates the nucleus accumbens - involved in emotion and cognition Mosharov et al 2009 = difference (reason why only nigrostriatal is damaged by Parkinsons) is that calcium channels regulate spontaneous activity of dopamine-producing cells in nigrostriatal system VS sodium channels in mesolimbic system alpha-synuclein, elevated intracellular calcium ions and intracellular dopamine levels combine to kill dopamine-releasing cells interference with any three factors prevents damage to cells because DA neurons of mesolimbic/mesocortical system don't have elevated levels of calcium ions so are spared

Answer 8

increased level of L-DOPA (precursor to dopamine) in brain causes remaining dopaminergic neurons to produce and secrete more dopamine so temporarily alleviate symptoms of disease BUT number of nigrostriatal dopaminergic neurons declines so symptoms become worse again and L-DOPA activates dopamine-producing neurons in mesolimbic system and produces side effects like hallucinations and delusions

Answer 9

increase in L-Dopa, but if uneffective neurosurgeons have stereotaxic procedures like: implant electrodes in Subthalmic Nucleus, and permit patient to electrically stimulate Motor Cortex deep brain stimulation of subthalamic nucleus (electrodes implanted in brain and wires under skin connect to stimulation devices implanted near collarbone) is as effective as brain lesions in suppressing tremors and has fewer adverse effects

Answer 10

destruction/removal of Globus Pallidus which inhibits motor cortex kaplitt et al 2007 = genetically modified virus into subthalamic nucleus of PD patients - it delivers a gene for enzyme (GAD) which produces inhibitory neurotransmitter, GABA, and turns excitatory neurones into inhibitory GABA-producing ones - decreased activity of GP and increased activity of motor area cortex

Answer 11

common form of dementia progressive loss of memory and other mental functions initial memory deficit involves recent events (like anterograde amnesia) long term memory is not always part of early alzheimers

Answer 12

10% of people 65+ have it 50% of those over 85 years

Answer 13

severe degeneration of hippocampus, entorhinal cortex, neocortex (especially the association cortex of frontal and temporal lobes) increase in sulci width (also seen in Down syndrome), and particularly wider sulci of temporal and parietal lobes, indicating degeneration of neocortex develop abnormal structures called amyloid plaques and neurofibrillary tangles in Alzheimer's disease, excess phosphate ions attach to strands of tau protein, changing its molecular structure develop abnormal filaments in soma and proximal dendrites of pyramidal cells in cerebral cortex, which disrupt transport of cell substances hence killing the cell and leaving behind a tangle of protein filaments

Answer 14

extracellular deposits which consist of a dense core of a protein called beta-amyloid, surrounded by degenerating axons and dendrites, and activated microglia and reactive astrocytes (cells involved in destruction of damaged cells)

Answer 15

dying neurons with intracellular accumulations of twisted tau protein filaments that formerly served as cell's internal skeleton providing the cell's transport system

Answer 16

stage 1 = perirhinal cortex and lateral portion of parahippocampal gyrus stage 2 = CA1 layer of hippocampus and subiculum stage 3 = higher levels of CA1 but none seen in other areas of cortex stage 4 = CA1 layer densely filled with tangles stage 5 = all hippocampus areas affected alongside associated areas of cortex like retrosplenial region and parietal lobe stage 6 = hippocampal formation "infested" with NFTs

Answer 17

alois alzheimer, german psychiatrist in 19th century, treated patient Frau D. for memory impairments and feelings of jealousy towards husband

Answer 18

HM damage to hippocampus (area associated with neurogenesis and spatial learning)

Answer 19

Fox et al (2001) did scans on patients with high risk of AD - evidence of reduced brain volume, especially in hippocampus and parietal lobe up to 5 years prior to AD diagnosis

Answer 20

Gomez-Isla et al. (1996) = brains of mild AD patients there's a 32% loss of neurones in entorhinal cortex Nestor et al. (2003) = reduced levels of activity in retrosplenial cortex in people with mild cognitive impairment these areas play a role in spatial learning

Answer 21

symptoms associated with spatial abilities rather than long term memory impairment 54% have difficulty recognising locations 30% of AD patients report difficulty finding their way around their home spatial disorientation first seen by family Delpolyi et al (2007) = patients with early stage AD made more mistakes on a newly learned route, particularly when asked to travel route in reverse - also impaired on maintaining sense of direction but not on tests of memory Lee et al (2006) = odd one out tasks (don't rely on memory) given to Alzheimers Disease (AD) and Semantic Dementia (SD) patients - SD patients show a progressive, cross-modal loss of semantic knowledge - both groups have damaged Medial Temporal Lobes but AD patients have more hippocampus damage - AD struggles to discriminate between similar scenes whilst SD struggles to discriminate similar faces

Answer 22

2003 tested alzheimer's patients on ability to recall a route through hospital subjects in wheelchair taken on specific 300m route around lobby for 4 minutes and told to pay attention AD patients became more lost than age matched controls and had more difficulty recognising landmarks on route subtest 3 was self-orientation/ability to form a cognitive map of landmarks related to one another and oneself - subjects told to sit down at either start or finish point -shown 10 photos of diff points of route and asked to point (eyes closed) in direction of this image, ignoring obstruction of any large furniture or walls - scored as correct if pointing was within 45 degrees of actual direction FINDINGS = older adults and alzheimer's disease groups scored lower than young and middle aged adults, but alzheimer's lower than older adults too

Answer 23

relieviating anxiety? nostalgia reduces anxiety and improves spatial ability? can increasing nostalgic cues help with spatial ability and wellbeing?

Answer 24

stage 1 = in cortex near bottom of brain, none in hippocampus stage 2 = throughout cortex except motor, only small levels in hippocampus stage 3 = all areas of cortex, higher levels in hippocampus Klunk et al (2003) developed PiB, a chemical that binds with beta amyloid and crosses blood-brain barrier to show accumulation of protein in cerebral cortex with PET scanner

Answer 25

defective form of beta amyloid produced by a gene encoding beta-amyloid precursor protein an enzyme beta secretase cuts the beta-amyloid precursor protein in two places, leaving a normally short beta amyloid protein but 5-10% are long form, but in alzheimer patients that rises to 40% long form fold over on themselves and form aggregations - misfolded proteins are toxic to cell long form beta-amyloid bind to receptors that respond to stress signals and stimulate apoptosis - basal forebrain Acetylcholinergic neurons have high levels of these receptors so once level of long form beta-amyloid reaches a high level, these neurons begin to die - Acetylcholinergic neurons are amongst first cells to be affected

Answer 26

can run in families St George-Hyslop et al (1987) found chromosome 21 contains a gene that produces beta-amyloid precursor protein - Down Syndrome is also associated with hgih levels of beta-amyloid deposits and is caused similarly by an extra 21st chromosome Hardy et al 1997 = abnormal beta-amyloid precursor protein genes cause defective long form of beta-amyloid to be produced

Answer 27

traumatic brain injury - people with closed head injuries reveal distribution of amyloid plaques - especially high in those with brain injuries and the ApoE4 gene (Bu, 2010) which interferes with removal of long form beta-amyloid obesity hypertension high cholesterol levels diabetes

Answer 28

2005 increases in beta-amyloid are first seen in regions of brain with highest default activity (neural activity that occurs when someone rests) strong relationship between regions of high default activity and beta-amyloid deposition, disrupted metabolism, and cortical atrophy in brains of Alzheimer's patients

Answer 29

pharmacological treatments = acetylcholinesterase inhibitors (ie donepezil, rivastigmine, galantamine) that inhibit destruction and enhance activity of acetylcholinesterase as acetylcholinergic neurons are some of the first to be damaged in Alzheimer's - these have a modest increase in cognitive ability but don't affect process of neural degeneration ALSO an NMDA receptor antagonist (memantine) is a noncompetitive NMDA receptor blocker that retards excitotoxic destruction of acetylecholinergic neurons caused by entry of excess calcium, relieving some symptoms of dementia

Answer 30

Schenk et al (1999) and Bard et al (2000) = injected alzheimer's disease mice with a vaccine that stimulated the immune system to destroy beta-amyloid and it suppressed the development of amyloid plaques when mice had received vaccine from early age and halted or even reversed plaque development in mice receiving vaccine later in life Monsonego and Weiner (2003) = clinical trial with alzheimer's patients attempted to destroy beta-amyloid by sensitising immune systems to it - 30 ppts with mild/moderate Alzheimer's given beta-amyloid injections - 23 generated antibodies against beta-amyloid, slowing down course of disease as immune systems destroyed beta-amyloid in brain Hock et al (2003) = compared cognitive abilities of patients who generated antibodies to those who didn't - antibody production reduced cognitive decline

Neurological Disorders Flashcards

(54 cards)