Neuropsychology Past Paper PDF

Task 8 - Neuropsychology Learning goals What are the possible causes of different types of brain damage? What could be the possible disorders behind the symptoms in the 3 cases? How does each of these diseases progress over time? Which neurotransmitters are involved in different psychiatric disorder...

Task 8 - Neuropsychology Learning goals What are the possible causes of different types of brain damage? What could be the possible disorders behind the symptoms in the 3 cases? How does each of these diseases progress over time? Which neurotransmitters are involved in different psychiatric disorders? What techniques can be used to discover brain damage? How does aging affect the brain? What are the possible causes of different types of brain damage? Cerebral vascular disorders Cerebral vascular disorders are caused by disease or damage to blood vessels. The damage causes reduction or total cutoff of flow of oxygen and glucose to a brain region. Such an interference causes all cells in the affected region to die after 10 minutes. A cerebral vascular accident (CVA) or stroke is the sudden appearance of neurological symptoms due to interrupted blood flow. Stroke often produces an infarct - an area of dead/dying tissue resulting from the obstruction of the blood vessels supplying the area. Surrounding the infarct is a dysfunctional area called the penumbra. The primary goal of treatment following stroke is to save the penumbra. A stroke can result from a wide variety of vascular disorders, but it is not a necessary consequence of vascular disorders. A small vascular lesion generally has a good prognosis of recovery of function. However, if there are preexisting lesions, th e new lesions can be cumulative and destroy a functional zone of brain tissue, producing serious deficits. Cerebral ischemia - a group of disorders in which symptoms are caused by the disruption of blood supply to an area of the brain. Thrombosis - a clot/plug in a blood vessel caused by the coagulation of blood. Embolism - A clot/plug brought from the blood from a larger vessel and forced into a smaller one, where it obstructs circulation. Cerebral arteriosclerosis - narrowing of arteries caused by thickening and hardening. Ischemia can be temporary, in which case it is called cerebral vascular insufficiency/transient ischemia. Migraine stroke - a transient ischemic attack which has a variety of neurological symptoms (e.g. impaired sensory function, skin numbness, difficulties in moving, aphasia), which depend on the affected vessels. Cerebral hemorrhage - massive bleeding in the brain ,which occurs when a cerebral blood vessel ruptures and blood seeps into the surrounding neural tissue and damages it. Prognosis is poor in cerebral hemorrhage, especially if the patient is unconscious for more than 48 hours. Angiomas - congenital (present from birth) collections of enlarged and twisting blood vessels that reroute the normal blood flow. Angiomas are supplied by 1 or more large arteries and drained by 1 or more large veins, most often located in the field of th e middle cerebral artery. Angiomas cause abnormalities in the amount and pattern of blood flow and are generally weak => they mad lead to stroke or an inadequate distribution of blood in the regions surrounding the vessels. Aneurisms - vascular widenings resulting from defects in a vessel's elasticity. Aneurisms are often accompanied with severe headaches that are present for years, because the aneurism is exerting pressure o n the dura mater, which has many pain receptors. Bursting aneurisms are a common cause of intracerebral hemorrhage. The symptoms of a stroke depend on the affected brain area, but common consequences are amnesia, aphasia (language difficulties), psychiatric disorders, dementia, paralysis and coma. Cerebral vascular diseases are associated with depression. Estimates of poststroke depression range from 25% to 50%. About 25% of stroke patients have poststroke anxiety. Treating cerebral vascular disorders Anticoagulant therapy - drug therapy used to remove/dissolve a clot. It used in ischemic episodes within 3 hours of the episode's onset. In can worsen bleeding, which is why it is not used in cases of bleeding. After a stroke, neuroprotectant drugs can be used to limit the changes leading to cell death. Treatments to reduce the processes that occur after a stroke include blood-pressure reducing drugs, salty solutions or steroids to reduce cerebral edema (accumulation of fluid in/around damaged tissue). The most effective approach to vascular disorders is prevention, achieved by a healthy lifestyle and drugs that control blood pressure. Traumatic brain injuries Body and Behavior Page 1  Traumatic brain injury (TBI) commonly results from accidents, sports and war injuries. It can affect brain function by directly damaging the brain: By disrupting blood supply; By inducing bleeding, increased intracranial pressure and swelling, thus opening the brain to infection; By scarring brain tissue, which can then become a focus for later epileptic seizures. PET scans indicate long-term reduction of brain activity (measured by glucose metabolism) following TBI (see figure to the right) Open head injuries - TBIs in which the skull is penetrated (e.g. in gunshot or missile wounds, or when fragments of bone penetrate the brain). Open head injuries produce highly specific symptoms resembling those of the surgical excision of a small area of cortex. The symptoms may undergo rapid and spontaneous recovery. Closed head injuries - TBIs that result from a blow to the head, which can subject the brain to a variety of mechanical forces. Coup - a bruise at the site of the site of the blow, caused by the bone's pushing inward, even when the skull is not fractured. Contrecoup - pressure from the coup may push the brain against the opposite side of the skull, producing an additional bruise. Microscopic lesions - twisting/cutting of nerve fibers. Hematoma - a growing mass of blood caused by a cerebral hemorrhage, which exerts pressure on surrounding structures. Edema - swelling, which exerts pressure on brain tissue. Closed head injuries are commonly accompanied by coma (loss of consciousness). The longer a coma lasts, the greater the possibility of serious impairment and death. Closed head injuries that damage the frontal and the temporal lobe tend to have significant effects on personality and social behavior. Closed head injuries can cause discrete impairments of the specific functions mediated by the cortex at the site of the The effects of even mild head injuries can be cumulative. For example, it is well- coup/contrecoup lesion or more generalized impairment established that a boxer will sustain a significant level of brain injury even though the from more widespread trauma throughout the brain. periods of unconsciousness may have been few and of short duration. Boxers who endure repeated concussion can subsequently suffer from dementia pugilistica (DP), The frontal and the temporal lobe are most susceptible to also called "boxer's dementia" or chronic traumatic encephalopathy (CTE). closed head injuries and discrete impairment is most commonly associated with these areas. More general impairment, resulting from microscopic lesions scattered throughout the brain is characterized by a loss of complex cognitive functions, including reductions in mental speed and concentration. Behavioral assessment of head injury After head injury, behavior is the most important measure of nervous system integrity. In the immediate postinjury period, the 2 most obvious behavioral symptoms are coma and amnesia. The Glasgow Coma Scale (GCS) is an objective indicator of the degree of unconsciousness that can be used as a measure of the depth of coma. The length of posttraumatic amnesia (PTA) is an alternative measure of an injury's severity. The duration of amnesia is correlated with later memory disturbance. Recovery from head injury Recovery from head trauma may continue for years, but the bulk of cognitive recovery takes place in the first 6-9 months. Recovering memory is slower than recovering general intelligence. The final level of memory performance is lower than other cognitive functions. People with brain stem damage have poorer cognitive outcomes. When deep impairments are detected, the prognosis for the recovery of cognitive functions is good, but the recovery of social skills or personality (which change often significantly following closed head injury) is not. Epilepsy Seizure - spontaneous, abnormal discharges of brain neurons as a result of scarring from injury, infections or tumors. Body and Behavior Page 2 Seizure - spontaneous, abnormal discharges of brain neurons as a result of scarring from injury, infections or tumors. Epilepsy - a brain disorder caused by seizures. Diagnosis of epilepsy requires is applied only to patients whose seizures are repeatedly generated by their own chronic brain dysfunction. Symptomatic seizures can be identified by a specific cause, such as infection, trauma, tumor, vascular malformation, toxic chemicals, very high fever, or other neurological disorder. Idiopathic seizures seem to arise spontaneously and in the absence of other CNS diseases. The circumstances that cause seizures are generally characterized by relative brain inactivity and the patient being still. 3 particular symptoms occur in many types of epilepsy: Onset of an epileptic aura - a psychological state (e.g. a bad smell, a specific thought, a feeling of familiarity, a hallucination or a tightness of the chest) that precedes and marks the onset of an epileptic seizure or migraine. Loss of consciousness - ranging from complete collapse to simply staring off into space. Often accompanied by amnesia in which the victim forgets the seizure itself and the period of lost consciousness. Movement - seizures often have a motor component. Some people shake; others exhibit automatic movements, such as rubbing the hands or chewing. The diagnosis of epilepsy is usually confirmed by EEG. However, 1 in 5 people has an abnormal EEG pattern - much more than the number of people thought to have epilepsy. Types of seizures A focal seizure begins from the point (focus) in the neocortex representing the region of the body where the movement is first seen, then spreads. Complex partial seizure - a type of focal seizure that originates mostly from the temporal lobe, but sometimes in the frontal lobe, characterized by 3 common manifestations: ○ Subjective experiences (e.g. repetitive thoughts, sudden alterations in mood, feelings of déjà vu or hallucinations) that predict the attack. ○ Automatisms - performing nonreflexive acts without conscious intention to do so (e.g. lip smacking, chewing or undoing buttons). ○ Postural changes (e.g. assuming a frozen posture). Generalized seizures - bilaterally symmetrical seizures without focal onset. They are characterized by loss of consciousness and by stereotyped motor activity. 1. Tonic stage - the body stiffens and breathing stops. 2. Clonic stage - rhythmic shaking occurs. 3. Post-seizure stage - loss of affect and confusion. It is estimated that ~50% of generalized seizures are preceded by an aura. Akinetic seizures - usually seen only in children. The child collapses suddenly and without warning. The seizure is often very short, and the child may get up after only a few seconds, but the fall can be dangerous. Myoclonic spasms - massive seizures that consist of a sudden flexion/extension of the body and often begin with a cry. Treating epilepsy Epilepsy is treated with anticonvulsant drugs, which inhibit the discharge of abnormal neurons by stabilizing their membrane. If medication fails to stop seizures, surgery can be performed to remove the focus of abnormal functioning in patients with focal seizures. Tumors A tumor/neoplasm is a mass of new tissue that persists and grows independently of its surrounding structures and has no physiological use. Benign tumors are not likely to recur after removal. Malignant tumors are often progressive and threaten life. Benign tumors are often inaccessible to the surgeon so they might be as serious as the malignant ones. Brain tumors do not grow from neurons, but from glia and other supporting cells. Encapsulated tumor - a tumor that grows in its own membrane and puts pressure on other parts of the brain. Due to the skull being fixed in size, any increase in its contents compress the brain, resulting in dysfunctions. Encapsulated tumors are particularly easy to identify on a CT scan. Infiltrating tumors are not clearly distinct from the surrounding tissue. They might destroy healthy cells and occupy their place or surround existing cells and interfere with their functioning. They are usually malignant tumors; any cancerous tissue that remains after surgery usually continues to grow. Gliomas - the most common malignant brain tumors that develop from glial cells. Meningiomas - non-glial brain tumors that grow between the meninges. They grow entirely outside the brain, are well encapsulated and are almost always benign. Meningiomas often disturb brain function by putting pressure on the brain, often producing seizures. They sometimes also erod e the overlying skull bone. Metastatic tumors - brain tumors that become established by a transfer of tumor cells by the bloodstream from some other region of the body. Metastasis - the transfer of disease from one organ/body part to another that is not directly connected. Brain tumors cause symptoms such as headache, vomiting, swelling of the optic disc (papilledema), slowing of the heart rate (bradycardia), mental dullness, double vision (diplopia), convulsions, and functional impairments due to brain damage where the tumor is located. Brain tumors are treated with surgery or radiation therapy. Chemotherapy has not yet been successful due to the blood-brain barrier. Body and Behavior Page 3 Brain tumors are treated with surgery or radiation therapy. Chemotherapy has not yet been successful due to the blood-brain barrier. Headache The pain-sensitive structures within the skull that can produce headache include the dura mater, the large arteries of the brain, the venous sinuses, some of the cranial nerves and some of the cervical nerves (nerves in the cervical spine). Pain can be elicited in these structures by pressure, displacement or inflammation. Migraine - a disorder characterized by recurrent attacks of headache. Classic migraine - begins with a visual aura that usually lasts for 20-40 minutes. The aura is thought to occur because narrowing of 1 or more cerebral arteries has produced ischemia of the occipital cortex. The actual headache being as the narrowing reverses and the dilation takes place. The headache is localized in one side of the head, although it often spreads on that side and sometimes extends to the opposite side as well. Common migraine - there is no clear aura, but a gastrointestinal or other signal may predict the attack. Cluster headache - unilateral pain in the head/face that lasts the initial symptoms are double vision, dropping o f the eyelid, weakness of voice, and difficulty chewing and swallowing or holding up the head. In some people, only the limbs are affected. Muscular weakness is caused by a failure of muscular neurotransmission due to a scarcity of muscle receptors for ACh. Receptors may have been attacked by antibodies from the patient's own immune system. Treatments includes ACh therapy, surgica l removal of the thymus to reduce antibody formation and immunosuppressive drugs. Poliomyelitis (polio) - an acute infectious disease caused by a virus with a special affinity for spinal cord motor neurons and sometimes cranial nerve motor neurons. Motor neuron loss causes paralysis and muscle wasting. If the motor neurons of the respiratory centers are attacked, death ca n result. Multiple sclerosis - a disorder characterized by loss of myelin, largely in motor tracts but also in sensory tracts. Sclerotic plaques - patches of small, hard scars, in which the myelin sheath and sometimes the axons are destroyed. Initial symptoms: loss of sensation in the face, limbs or body; blurring of vision; loss of sensation and control in 1 or mor e limbs. The initial symptoms often go into remission, not appearing again for years. However, the disease may progress rapidly in jus t a few years until an Body and Behavior Page 4  The initial symptoms often go into remission, not appearing again for years. However, the disease may progress rapidly in jus t a few years until an affected person is limited to bed care. Causes of MS are unknown. Paraplegia - paralysis of both lower limbs caused by a complete transection of the spinal cord. Quadriplegia - paralysis of all 4 limbs. After the cord has been severed, all activity stops in the part distal to the cut, and all movement, sensation and reflexes distal to the cut disappear. Spinal shock - absence of thermoregulatory and bladder control, which lasts for 4 days to about 6 weeks after severing the spinal cord. Gradually, some spinal reflexes return until a stabilized condition is reached after around a year. No sensation, voluntary movements, or thermoregulatory control ever reappears below the lesion. Brown-Sequard syndrome - the consequences of a unilateral transection through the spinal cord. Different symptoms appear on the 2 sides of the body below the cut due to the fact that some pathways cross the spinal cord and others do not. Walking ability is regained within 2-3 days because it is controlled bilaterally. Hemiplegia - loss of voluntary movements on one side of the body and changes in postural tone and in various reflexes. It results from damage to the neocortex and basal ganglia contralateral to the motor symptoms. Which neurotransmitters are involved in different psychiatric disorders? Psychiatric disorder - a disorder of psychological function sufficiently severe to require treatment. Schizophrenia Schizophrenia is a severe psychiatric disorder characterized by the DSM-5 as the presence of at least 2 of the following for 6 months, including >=1 month of active symptoms: Delusions - beliefs that distort reality. Hallucinations - altered perceptions such as hearing voices, for which there are no appropriate external stimuli. Disorganized speech - such as incoherent statements or senseless rhyming. Disorganized / excessively agitated behavior Other symptoms that cause social or occupational dysfunction. Type 1 (positive) symptoms - delusions, hallucinations and/or disorganized/bizarre behavior. Type 2 (negative) symptoms - flat affect, social withdrawal, poverty of speech, reduction/absence of motivation. Cognitive deficits can be seen in working and episodic memory, language, executive function, attention and sensory processing. Schizophrenia symptoms typically develop in late adolescence. People who develop schizophrenia are much more likely to have experienced adverse events in prenatal (before birth) and perinatal (during and immediately after birth) life. Most patients stay at a fairly stable level after the first few years of symptoms, with little evidence of declining neuropsychological functioning. Structural abnormalities in schizophrenic brains Schizophrenic brains weigh less than healthy brains and have larger ventricles. They also have fewer neurons in the prefrontal cortex, as well as thinner hippocampal gyri. Neurons in the dorsolateral prefrontal cortex (DLPFC) have a simple dendritic organization, indicating fewer synapses than typical. In the DLPFC, a subpopulation of GABA neurons shows a reduced GABA synthesis associated with poor working memory. Pyramidal neurons in the hippocampus show haphazard unsystematic orientations. The prefrontal cortex of patients with schizophrenia is functionally abnormal as Body and Behavior Page 5  The prefrontal cortex of patients with schizophrenia is functionally abnormal as well, which is confirmed by several studies. Biochemical abnormalities in schizophrenic brains Dopamine theory of schizophrenia - schizophrenia is partly caused by too much dopamine and antipsychotic drugs exert their effects by decreasing dopamine levels. More specifically, it is believed that schizophrenia is partly caused by hyperactivity specifically at D2 receptors, rather than at dopamine receptors in general. Antipsychotic drugs are meant to treat certain symptoms of schizophrenia and bipolar disorder. Psychosis - a loss of touch with reality. Drugs such as amphetamine and cocaine, which can trigger episodes that resemble schizophrenia in healthy users, increase the extracellular levels of dopamine and other monoamines in the brain. There are also abnormalities in glutamate and GABA and their receptors. There is a high variation in the degree of different abnormalities in individual patients and the relationship between the neurochemical variations and the specific symptoms is still unknown. Mood disorders Major/clinical depression is a disorder characterized by prolonged feelings of worthlessness and guilt, disruption of normal eating habits, sleep disturbances, a general slowing of behavior, and frequent thoughts of suicide. Reactive depression - depression triggered by an obvious negative experience. Endogenous depression - depression with no apparent cause. The best-established neurochemical abnormality in depression is oversecretion of cortisol by the adrenal glands. Cortisol is associated with stress reactions. When a person is stressed, the hypothalamus secretes corticotrophin-releasing hormone, which stimulates the pituitary to produce adrenocorticotropin (ACTH). ACTH circulates through the blood and stimulates the adrenal gland to produce cortisol. The hypothalamic neurons that begin this cascade are regulated by norepinephrine neurons in the locus coeruleus (a nucleus in the pons). Postmortem and structural MRI studies have found reduced gray matter of anterior cingulate cortex, posterior orbitofrontal cortex, nucleus accumbens, hippocampus in both depression and bipolar disorder. Imaging also reveals a loss of glia and synapses in the anterior cingulate cortex, DLPFC and amygdala. Depressive symptoms correlate with an abnormal increase in glucose metabolism in the amygdala. Activity in the amygdala stimulates cortisol release. Monoamine theory of depression - depression is associated with underactivity at serotonergic and noradrenergic synapses. Neuroplasticity theory of depression - depression results from a decrease of neuroplastic processes in various brain structures (e.g. hippocampus), which leads to neuron pathology. Depression is associated with a decrease in adult hippocampal neurogenesis. Antidepressants increase the synthesis of neurotrophins (proteins that regulate development, maintenance and function of neurons). Brain-derived neurotropic factor (BDNF) levels are increased by treatments (both pharmacological and non-pharmacological) that improve depression. Bipolar disorder is a psychiatric disorder characterized by alternating periods of and hypomania (a reduced need for sleep, high energy and positive affect) or mania (a mental state of extreme excitement characterized by excessive euphoria - extreme hypomania). Bipolar disorder type II - characterized by bouts of depression and hypomania. Bipolar disorder type I - characterized by bouts of depression and mania (and potentially also hypomania). The mood episodes of bipolar disorders can last weeks to months. Study: a positive relation was found between number of bipolar episodes and amount of loss of gray matter in the temporal lob e (fusiform gyrus and hippocampus) and cerebellum => suggests that bipolar disorder has a progressive neurodegenerative aspect. A set of models of bipolar disorder is that a bipolar patient's brain is especially sensitive to the effects of stressors or drugs and that episodes of mood disorder actually change the brain. Such a model is the drug- or stress-induced sensitization model, which is supported by the following facts: Large individual differences appear in the degree of sensitization and drug effects in laboratory animals and people => genetically predisposed individuals may be especially sensitive and produce faster/larger neuronal changes in response to stressors. Abuse of psychomotor stimulants (e.g. cocaine) is associated with manic episodes. Individuals who are bipolar are at a higher risk for substance abuse (suggesting that they are especially sensitive to drug e ffects). In bipolar patients, there is evidence of disruption of the hypothalamic-pituitary-adrenal (HPA) axis and circadian rhythms. There are also alterations to GABA, glutamate, and dopamine neurotransmission and there is evidence of lower BDNF levels when patients are either depressed or manic. Body and Behavior Page 6 Mood stabilizers - drugs that effectively treat depression or mania without increasing the risk of mania or depression, respectively. Anxiety disorders Anxiety disorders are characterized by intense fear/anxiety disproportional to the circumstances and disrupts normal functioning. The link between all recognized anxiety disorder is fear. It is believed that the anterior cingulate cortex, medial prefronta l cortex, orbitofrontal cortex and hippocampus, which are responsible for controlling fear reactions generated by the amygdala, are not functioning p roperly in people with anxiety disorders. Generalized anxiety disorder - characterized by extreme feelings of anxiety and worry about a large number of different activities or events. Specific phobias - a strong fear or anxiety about particular objects or situations, which leads to avoidance of those specific objects/situations. Agoraphobia - a pathological fear of public and open spaces. It is considered to be more disabling than most specific phobias, which is why it has its own category. Panic disorder - recurrent rapid-onset attacks of extreme fear and severe symptoms of stress (panic attacks). Multiple sclerosis Multiple sclerosis (MS) is a progressive disease that attacks the myelin of axons in the CNS. First symptoms (microscopic areas of degeneration of myelin sheaths) appear in early adulthood. Eventually damage to the myelin is so severe that the associated axons become dysfunctional and degenerate. Ultimately, many areas of hard scar tissue develop in the CNS (sclerosis means hardening). The general consensus is that the progression of MS is driven by an interaction between immune-system reactivity and neural degeneration. In MS there is also a lack of remyelination of neurons (the generation of new myelin sheaths on axons, which is usually done by oligodendrocytes) and generation of new oligodendrocytes. Both processes occur throughout a healthy person's lifespan. Common symptoms of MS are visual disturbances, muscular weakness, numbness, tremor and ataxia (loss of motor coordination). In addition, cognitive deficits and emotional changes occur in some patients. Established risk factors for MS are vitamin D deficiency, exposure to the Epstein-Barr virus and cigarette smoking. MS is typically diagnosed with MRI. Dementias Dementia is an acquired and persistent syndrome of intellectual impairment. The DSM-5 splits dementias into 2 categories: major neurocognitive disorder (NCD) and mild neurocognitive disorder (mild NCD). NCD is defined by the DSM-5 as: Evidence of substantial cognitive decline from a previous level of performance based upon the concerns of the individual, a k nowledgeable informant or the clinician A decline in neurocognitive performance, typically involving test performance in the range of >=2 standard deviations below a ppropriate norms on formal testing or equivalent clinical evaluation" (DSM-5). The cognitive deficits must be sufficient to interfere with independent functioning and must not be attributable to another m ental disorder. Mild NCD is defined similarly, but: The cognitive decline from a previous performance level is modest A decline in neurocognitive test performance is between 1 and 2 standard deviations Cognitive deficits do not interfere with functioning independently. Alzheimer's disease - the most prevalent form of dementia is (accounts for about 65% of all dementias in people over 65). Alzheimer's is characterized by a slow onset and steady progress. It first robs a person of recent memory, then of more remot e memory, and finally of the abilities to recognize family members and to function independently. Preclinical stage - involves pathological changes in the brain without any behavioral or cognitive symptoms. Prodromal stage - involves mild cognitive impairment. At this point, the combined presence of mild cognitive impairment and some biological changes can lead to a fairly reliable diagnosis. Dementia stage - starts with a progressive decline in memory, deficits in attention and personality changes, followed by marked confusion, irritability, anxiety, and deterioration of speech. Eventually simple responses such as swallowing and bladder control become difficult. Body and Behavior Page 7  irritability, anxiety, and deterioration of speech. Eventually simple responses such as swallowing and bladder control become difficult. Anatomical correlates of Alzheimer's disease Neuritic (amyloid) plaques (a.k.a. senile plaques) are found mainly in the cerebral cortex and result from the accumulation of tau protein. Their concentration in the cortex is correlated with the magnitude of cognitive deterioration. Neuritic plaques consists of a central core of protein material known as beta-amyloid, surrounded by degenerative cellular fragments of neurons (e.g. axonal and dendritic processes). Neurofibrillary tangles are threadlike tangles of tau protein in the neural cytoplasm found mostly in the medial temporal lobe (entorhinal cortex, amygdala and hippocampus). They have also been observed in patients with Down syndrome, Parkinson's disease, and other dementias. The neocortex shrinks, losing up to 1/3 of its volume as the disease progresses. Some areas are relatively spared (see figure A to the right). The limbic system undergoes the most severe degenerative changes in Alzheimer's disease. From the limbic structures, the entorhinal cortex is affected earliest and the most severely. The entorhinal cortex is the major relay through which information flows between the neocortex and the hippocampus and related structures. Damage to the entorhinal cortex is associated with memory loss, which is the enduring symptom of Alzheimer's disease. In Alzheimer's disease, noradrenaline, dopamine, and serotonin, as well as some glutamate receptors, are reduced. Age-matched controls also show reduction in transmitter levels, but patients with Alzheimer's disease distinguish themselves from the control groups by showing greater reductions in >=2 neurotransmitters. In Alzheimer's disease there is a shrinkage of large neurons. However, the most widespread cause of cortical atrophy appears to be a loss of dendritic arborization (branching). Early-onset patients (before age 65) have more diffuse atrophy across the cerebral hemispheres but less atrophy in the hippocampus than late-onset patients (age 65 and older). Motor disorders Motor disorders are marked by abnormalities in movement and posture. However, they also include cognitive changes, which become more marked as the disorder progresses. Hypokinetic-rigid syndrome - a group of motor disorders that is characterized by loss of movement. Hyperkinetic-dystonic syndrome - a group of motor disorders that is characterized by increased motor activity. Hyperkinetic disorders Huntington's disease - a progressive motor disorder that results in intellectual deterioration and personality changes as well as abnormal movements called choreas. The first symptoms usually appear in people 30 to 50 years of age (but can also occur earlier). The first unvoluntary movemen ts usually appear within a year of the onset of behavioral symptoms. Behavioral symptoms include impairment of recent memory, defective ability to manipulate acquired knowledge and slowed inform ation processing. Emotional changes include anxiety, depression, mania and schizophrenia-like symptoms. Eventually, motor and cognitive deterioration become so severe that patients are incapable of feeding themselves or recognizi ng their relatives. There is no cure and death typically occurs about 20 years after the appearance of the first symptoms. Huntington's disease is transmitted genetically by a single mutated dominant gene called huntingtin, which codes for huntingtin protein. Half of the affected person's offspring will develop the disease. At autopsy, the brains of people with Huntington's disease show cortical shrinkage and thinning. The basal ganglia are atrophied and show significant neuronal loss. A dominant explanation of the disease is an imbalance among the various neurotransmitter systems o f the basal ganglia. Body and Behavior Page 8 Tourette's syndrome starts with tics (involuntary, repetitive, stereotyped movements or vocalizations), which are then joined by inarticulate cries, and finally by coprolalia (obscene speech) and echolalia (repeating what others said and other actions). People with Tourette's syndrome can be intelligent and productive and are not neurotic or psychotic. Patients with the disorder tend to have smaller striatal volumes. The condition is improved with dopamine antagonists. Patients are also taught how to suppress the ticks, which is effective in most cases. Tourette's is sometimes viewed as the r esult of a dysfunctional caudate that is unable to suppress unwanted movements, like tics. There is also evidence of dysfunctional dopaminergic and GABAergic signaling within the cortical-striatal-thalamic-cortical brain circuits, which are implicated in motor learning (including habit formation). Hypokinetic disorders Parkinson's disease is characterized by positive symptoms (the acquisition of abnormal behaviors) and negative symptoms (the loss of normal behaviors). Positive symptoms: ○ Tremor at rest; ○ Muscular rigidity - simultaneously increased muscle tone in both extensor and flexor muscles; ○ Involuntary movements - such as continuous changes in posture for no apparent reason. Negative symptoms: ○ Postural disorders - difficulties in maintaining a body part in its normal position in relation to other body parts (disorder of fixation) or difficulties in in standing or even sitting unsupported (disorders of equilibrium). ○ Righting disorders - difficulties in standing when lying or even rolling over. ○ Locomotive disorders - difficulties in initiating stepping due to troubles maintaining equilibrium when shifting weight from one limb to the other. ○ Speech disturbances - the most noticeable being a complete absence of tone in the speaker's voice ○ Akinesia - A poverty of movement that may manifest in a blank facial expression or lack of blinking; difficulties in making repetitive movements, such as tapping. Psychological symptoms: many patients have cognitive symptoms that mirror their motor symptoms: ○ Poverty of feeling, libido, motive and attention. People may sit for hours, apparently lacking the will to enter any course of activity. ○ Thinking is slowed and is easily confused with dementia because patients do not process the content of conversations. In fact, they are simply processing very slowly. ○ Cognitive slowing is similar to changes seen in Alzheimer's disease. Postmortem studies show Alzheimer-like abnormalities in most patients, even if they had no obvious signs of dementia. Idiopathic Parkinson's disease's cause is unknown. It most often develops in people older than 50 years of age. Postencephalitic Parkinson's disease originated in the sleeping sickness that existed between 1916 and 1927. A unique pattern of brain damage was the death of cells in the substantia nigra. Drug-induced Parkinson's disease is associated with ingesting various drugs, such as major tranquillizers. The symptoms are usually reversible. Symptoms of Parkinson's disease begin subtly with a tremor in one hand or slight stiffness in the distal parts of the limbs. Later, movements may slow, the face losing emotional expression. Thereafter, the body may become stooped; speech may slow and become monotonous; difficulty in swallowing saliva may result in drooling. It usually takes 10-20 years before symptoms lead to disability. Symptoms may appear suddenly and disappear just as suddenly. Partial remission may occur in response to interesting/stimulating situations. Parkinson's disease is not entirely inherited, but ~25% of people with the disease have a living relative with the disease. The brains of deceased individuals with Parkinson's disease show more than 90% reduction of dopamine amount in the brain. Decreases in norepinephrine have also been recorded. Parkinson's disease is associated with widespread degeneration, but it is particularly severe in the substantia nigra. Autopsy often reveals Lewy bodies - clumps of a protein called alpha-synuclein in the surviving dopaminergic neurons of the substantia nigra. No known cure exists for Parkinson's disease because the factors that produce the progressive degeneration of the substantia nigra are not yet known. Treatment is directed toward support and comfort. A person's outcome is strongly affected by how well they cope (psychologically) with the disability => patients are counselled early regarding the meaning of the symptoms and the potential to lead long/productive lives. Pharmacological treatment focuses on increasing activity in remaining dopamine synapses and suppressing the activity in structures that show higher activity in the absence of adequate dopamine action. L-Dopa, which is converted into dopamine in the brain, enhances effective dopamine transmission. Anticholinergic drugs are used to suppress cholinergic systems that show higher activity in the absence of adequate dopamine activity. Dementia in Parkinson's disease (article): Dementia affects about 40% of patients with Parkinson's disease. The prevalence is very low in younger patients and very high in older patients. The risk factors associated with dementia in PD are advanced age, advanced age of onset of motor symptoms, presence of depres sion, current smoking, poor cognitive test scores, severe motor symptoms, confusion or psychosis while being treated with L -Dopa, occurrence of early drug- related hallucinations, poor verbal fluency. Dementia associated with PD is mainly characterized by dysexecutive syndrome (impairment of executive functioning - mental processes that enable planning, focusing attention, remembering instructions and multitasking), visual perception and memory (different from the amnesia seen in patients with Alzheimer's disease). The memory impairments are thought to be a result of difficulties in accessing stored mem ories due to the Body and Behavior Page 9  patients with Alzheimer's disease). The memory impairments are thought to be a result of difficulties in accessing stored mem ories due to the impairment of executive functioning, rather than an inability to store new memories. Some PD patients may also develop another type of dementia (in addition to a dysexecutive syndrome) with a limbic/hippocampal type of amnesia, which is sometimes associated with early impairment of language similar to that of patients with Alzheimer's. Demented patients with PD also display impaired verbal fluency and naming difficulties, but it is thought that these deficien cies are related to the dysexecutive syndrome, rather than to a deterioration of language functions. All demented patients with PD have personality changes and depressive symptoms and hallucinations are more common in demented patients with PD than those with Alzheimer's disease. Cognitive dysfunction in PD correlates strongly with motor symptoms that respond little to L-Dopa => dopaminergic deficit is not the main neurochemical impairment responsible for dementia in PD. There are studies that suggest the involvement of noradrenergic and serotonergic pathways as the cause of cognitive impairment. There is substantial evidence that degeneration of the ascending cholinergic pathways may significantly contribute to cognitive impairment and dementia in patients with PD. A deficit in cholinergic innervation of the cerebral cortex has been correlated with the level of cognitive impairment and presence of dementia. Demented patients with PD have more cell loss in the medial substantia nigra and more severe lesions similar to the ones in Alzheimer's disease in the isocortex and hippocampus than non-demented patients. The presence of dementia in PD patients correlates strongly with the presence of AD-type pathology (such as amyloid plaques). There is evidence that cholinesterase inhibitors might be beneficial in the treatment of dementia in PD. However, this evidence is mainly from small studies. Body and Behavior Page 10