Berger , 1925 (1929. Arch.Psychiatr.) Ümmühan İşoğlu-Alkaç

1. States of Brain Activity-Sleep and Brain Waves Berger, 1925 (1929. Arch.Psychiatr.) Ümmühan İşoğlu-Alkaç Yeditepe University, Faculty of Medicine 28.03.2014

2. Why EEG based measurements? • EEG-based measurements • Non-invasive scalp recordings • Well-controlled cognitive experiments in human subjects • High temporal resolution • Poor spatial resolution • Fusion possibility with neuroimaging modalities with high spatial resolution • Intracranial EEG measurements in Epileptic Patients

3. Brain Waves Electrical recordings from the surface of the brain oreven from the outer surface of the head demonstratethat there is continuous electrical activity in the brain.Both the intensity and the patterns of this electricalactivity are determined by the level of excitation of differentparts of the brain resulting from sleep, wakefulness,or brain diseases such as epilepsyor evenpsychoses. The undulations in the recorded electricalpotentials, are called brain waves,and the entire record is called an EEG(electroencephalogram).

4. Brain Waves The intensities of brain waves recorded from thesurface of the scalp range from 0 to 200 microvolts, andtheir frequencies range from once every few seconds to50 or more per second. The character of the waves isdependent on the degree of activity in respective partsof the cerebral cortex, and the waves change markedlybetween the states of wakefulness and sleep and coma.Much of the time, the brain waves are irregular, andno specific pattern can be discerned in the EEG.

6. Elektroensefalogram (EEG)

7. In normal healthy people, most waves in the EEG canbe classified as beta, alpha, theta, and delta waves. Alpha wavesare rhythmical waves that occur at frequenciesbetween 8 and 16 cycles per second and arefound in the EEGs of almost all normal adult peoplewhen they are awake and in a quiet, resting state ofcerebration.These waves occur most intensely in the occipitalregion but can also be recorded from the parietaland frontal regions of the scalp. Their voltage usually isabout 50 microvolts. During deep sleep, the alpha wavesdisappear. When the awake person’s attention is directed tosome specific type of mental activity, the alpha wavesare replaced by asynchronous, higher-frequency butlower-voltage beta waves.

8. Beta wavesoccur at frequencies greater than 16 cyclesper second and as high as 80 cycles per second.They arerecorded mainly from the parietal and frontal regionsduring specific activation of these parts of the brain. Theta waveshave frequencies between 4 and 7 cyclesper second. They occur normally in the parietal andtemporal regions in children, but they also occur duringemotional stress in some adults, particularly during disappointmentand frustration. Theta waves also occur inmany brain disorders, often in degenerative brain states.

9. Delta wavesinclude all the waves of the EEG withfrequencies less than 3.5 cycles per second, and theyoften have voltages two to four times greater than mostother types of brain waves. They occur in very deepsleep, in infancy, and in serious organic brain disease. They also occur in the cortex of animals that have hadsubcortical transections separating the cerebral cortexfrom the thalamus. Therefore, delta waves can occurstrictly in the cortex independent of activities in lowerregions of the brain.

10. Origin of Brain Waves The discharge of a single neuron or single nerve fiberin the brain can never be recorded from the surface ofthe head. Instead, many thousands or even millions ofneurons or fibers must fire synchronously; only then willthe potentials from the individual neurons or fiberssummate enough to be recorded all the way through theskull. Thus, the intensity of the brain waves from thescalp is determined mainly by the numbers of neuronsand fibers that fire in synchrony with one another, notby the total level of electrical activity in the brain. Infact, strong nonsynchronousnerve signals often nullifyone another in the recorded brain waves because ofopposing, when the eyes were closed, synchronousdischarge of many neurons in the cerebral cortex at afrequency of about 12 per second, thus causing alphawaves. Then, when the eyes were opened, the activity ofthe brain increased greatly, but synchronization of thesignals became so little that the brain waves mainly nullifiedone another, and the resultant effect was very lowvoltage waves of generally high but irregular frequency,the beta waves

11. Origin of Alpha Waves. Alpha waves will not occur in thecerebral cortex without cortical connections with thethalamus. Conversely, stimulation in the nonspecificlayer of reticular nuclei that surround the thalamus orin “diffuse” nuclei deep inside the thalamus often setsup electrical waves in the thalamocortical system at afrequency between 8 and 13 per second, which is thenatural frequency of the alpha waves. Therefore, it isbelieved that the alpha waves result from spontaneousfeedback oscillation in this diffuse thalamocorticalsystem, possiblyincluding the reticular activatingsystemin the brain stem as well. This oscillation presumablycauses both the periodicity of the alpha wavesand the synchronous activation of literally millions ofcortical neurons during each wave.

12. Origin of Delta Waves. Transection of the fiber tracts fromthe thalamus to the cerebral cortex, which blocks thalamicactivation of the cortex and thereby eliminates thealpha waves, nevertheless does not block delta waves inthe cortex. This indicates that some synchronizing mechanismcan occur in the cortical neuronal system byitself—mainly independent of lower structures in thebrain—to cause the delta waves. Delta waves also occur during deep slow-wave sleep;this suggests that the cortex then is mainly releasedfrom the activating influences of the thalamus and otherlower centers.

13. Effect of Varying Levels ofCerebral Activity on the Frequency of the EEG There is a general correlation between level of cerebralactivity and average frequency of the EEG rhythm, theaverage frequency increasing progressively with higherdegrees of activity. The delta waves in stupor,surgical anesthesia, and deep sleep; theta waves inpsychomotor states and in infants; alpha waves duringrelaxed states; and beta waves during periods of intensemental activity. During periods of mental activity, thewaves usually become asynchronous rather than synchronous,so that the voltage falls considerably, despitemarkedly increased cortical activity.

15. Sleep Sleep is defined as unconsciousness from which the person can be aroused bysensory or other stimuli. It is to be distinguished from coma, which is unconsciousnessfrom which the person cannot be aroused. There are multiple stagesof sleep, from very light sleep to very deep sleep; sleep researchers also dividesleep into two entirely different types of sleep that have different qualities.

16. Two Types of Sleep They are called • slow-wave sleep,because in this type of sleep the brain waves are very strong and very low frequency,and • rapid eye movement sleep (REM sleep), because in this type of sleep the eyes undergo rapid movements despite the factthat the person is still asleep.

17. Two Types of Sleep Most sleep during each night is of the slow-wave variety; this is the deep,restful sleep that the person experiences during the first hour of sleep afterhaving been awake for many hours. REM sleep, on the other hand, occurs inepisodes that occupy about 25 per cent of the sleep time in young adults; eachepisode normally recurs about every 90 minutes (5-30 min). This type of sleep is not sorestful, and it is usually associated with vivid dreaming.

18. Slow-Wave Sleep Most of us can understand the characteristics of deep slow-wave sleep byremembering the last time we were kept awake for more than 24 hours andthen the deep sleep that occurred during the first hour after going to sleep. Thissleep is exceedingly restful and is associated with decrease in both peripheralvascular tone and many other vegetative functions of the body.For instance,there are 10 to 30 per cent decreases in blood pressure, respiratory rate, andbasal metabolic rate. Although slow-wave sleep is frequently called “dreamless sleep,” dreams andsometimes even nightmares do occur during slow-wave sleep. The differencebetween the dreams that occur in slow-wave sleep and those that occur in REMsleep is that those of REM sleep are associated with more bodily muscleactivity, and the dreams of slow-wave sleep usually are not remembered. Thatis, during slow-wave sleep, consolidation of the dreamsin memory does not occur.

19. REM Sleep (Paradoxical Sleep, Desynchronized Sleep) In a normal night of sleep, bouts of REM sleep lasting5 to 30 minutes usually appear on the average every90 minutes. When the person is extremely sleepy, eachbout of REM sleep is short, and it may even be absent.Conversely, as the person becomes more restedthrough the night, the durations of the REM boutsincrease. There are several important characteristics of REMsleep: 1. It is usually associated with active dreaming andactive bodily muscle movements. 2. The person is even more difficult to arouse bysensory stimuli than during deep slow-wave sleep,and yet people usually awaken spontaneously inthe morning during an episode of REM sleep. 3. Muscle tone throughout the body is exceedinglydepressed,indicating strong inhibition of thespinal muscle control areas.

20. 4. Heart rate and respiratory rate usually becomeirregular, which is characteristic of the dreamstate. 5. Despite the extreme inhibition of the peripheralmuscles, irregular muscle movements do occur.These are in addition to the rapid movements ofthe eyes. 6. The brain is highly active in REM sleep, andoverall brain metabolism may be increased asmuch as 20 per cent. The electroencephalogram(EEG) shows a pattern of brain waves similar tothose that occur during wakefulness. This type ofsleep is also called paradoxical sleepbecause it isa paradox that a person can still be asleep despite marked activity in the brain. In summary, REM sleep is a type of sleep in whichthe brain is quite active. However, the brain activity isnot channeled in the proper direction for the personto be fully aware of his or her surroundings, and thereforethe person is truly asleep.

21. Basic Theories of SleepSleep Is Believed to Be Caused by an Active Inhibitory Process. An earlier theory of sleep was that the excitatory areasof the upper brain stem, the reticular activating system,simply fatigued during the waking day and becameinactive as a result. This was called the passive theoryof sleep. An important experiment changed this viewto the current belief that sleep is caused by an activeinhibitory process: it was discovered that transectingthe brain stem at the level of the midpons creates abrain whose cortex never goes to sleep. In other words,there seems to be some center located below the midpontilelevel of the brain stem that is required to causesleep by inhibiting other parts of the brain.

22. Neuronal Centers, Neurohumoral Substances,and Mechanisms That Can Cause Sleep—A Possible Specific Role for Serotonin • The most conspicuous stimulation area for causingalmost natural sleep is the raphe nuclei in thelower half of the pons and in the medulla. Nerve fibers from these nucleispread locally in the brain stem reticularformation and also upward into the thalamus,hypothalamus, most areas of the limbic system,and even the neocortex of the cerebrum.. It isalso known that many nerve endings of fibersfrom these raphe neurons secrete serotonin.When a drug that blocks the formation ofserotonin is administered to an animal, the animaloften cannot sleep for the next several days. Therefore, it has been assumed that serotonin is atransmitter substance associated with productionof sleep.

23. 2. Stimulation of some areas in the nucleus of thetractus solitariuscan also cause sleep. This nucleusis the termination in the medulla and pons forvisceral sensory signals entering by way of thevagus and glossopharyngeal nerves. 3. Stimulation of several regions in the diencephaloncan also promote sleep, including (1) the rostralpart of the hypothalamus, mainly in thesuprachiasmal area, and (2) an occasional area inthe diffuse nuclei of the thalamus.

24. Lesions in Sleep-Promoting Centers Can Cause Intense Wakefulness. Discrete lesions in the raphe nucleilead to ahigh state of wakefulness. This is also true of bilaterallesions in the medial rostral suprachiasmal area in theanterior hypothalamus Indeed, sometimeslesions of the anterior hypothalamus can cause suchintense wakefulness that the animal actually dies ofexhaustion.

25. Other Possible Transmitter Substances Related to Sleep. Experiments have shown that the cerebrospinal fluidas well as the blood or urine of animals that have beenkept awake for several days contains a substance orsubstances that will cause sleep when injected into thebrain ventricular system of another animal. One likelysubstance has been identified as muramyl peptide, a low-molecular-weight substance that accumulates inthe cerebrospinal fluid and urine in animals keptawake for several days.When only micrograms of thissleep-producing substance are injected into the thirdventricle, almost natural sleep occurs within a fewminutes, and the animal may stay asleep for severalhours. Another substance that has similar effects incausing sleep is a nonapeptide isolated from the bloodof sleeping animals. And still a third sleep factor, notyet identified molecularly, has been isolated from theneuronal tissues of the brain stem of animals keptawake for days. It is possible that prolonged wakefulnesscauses progressive accumulation of a sleep factoror factors in the brain stem or in the cerebrospinalfluid that lead to sleep.

26. Possible Cause of REM Sleep. Why slow-wave sleep isbroken periodically by REM sleep is not understood.However, drugs that mimic the action of acetylcholineincrease the occurrence of REM sleep. Therefore, ithas been postulated that the largeacetylcholinesecretingneurons in the upper brain stem reticular formationmight, through their extensive efferent fibers,activate many portions of the brain. This theoreticallycould cause the excess activity that occurs in certainbrain regions in REM sleep, even though the signalsare not channeled appropriately in the brain to causenormal conscious awareness that is characteristic ofwakefulness.

27. Cycle Between Sleep and Wakefulness The preceding discussions have merely identifiedneuronal areas, transmitters, and mechanisms that arerelated to sleep. They have not explained the cyclical,reciprocal operation of the sleep-wakefulness cycle.There is as yet no explanation. Therefore, we can letour imaginations run wild and suggest the followingpossible mechanism for causing the sleep-wakefulnesscycle.When the sleep centers are not activated, the mesencephalicand upper pontile reticular activatingnuclei are released from inhibition, which allows thereticular activating nuclei to become spontaneously active.This in turn excites both the cerebral cortex andthe peripheral nervous system, both of which sendnumerous positive feedback signals back to the samereticular activating nuclei to activate them still further. Therefore, once wakefulness begins, it has a naturaltendency to sustain itself because of all this positivefeedback activity.

28. Then, after the brain remains activated for manyhours, even the neurons themselves in the activatingsystem presumably become fatigued. Consequently,the positive feedback cycle between the mesencephalicreticular nuclei and the cerebral cortex fades,and the sleep-promoting effects of the sleep centerstake over, leading to rapid transition from wakefulnessback to sleep. This overall theory could explain the rapid transitionsfrom sleep to wakefulness and from wakefulnessto sleep. It could also explain arousal, the insomniathat occurs when a person’s mind becomes preoccupiedwith a thought, and the wakefulness that is producedby bodily physical activity.

29. Physiologic Effects of Sleep Sleep causes two major types of physiologic effects: first, effects on the nervous system itself, and second,effects on other functional systems of the body. Thenervous system effects seem to be by far the moreimportant because any person who has a transectedspinal cord in the neck (and therefore has no sleepwakefulnesscycle below the transection) shows noharmful effects in the body beneath the level of transection that can be attributed directly to a sleepwakefulnesscycle. Lack of sleep certainly does, however, affect thefunctions of the central nervous system. Prolongedwakefulness is often associated with progressive malfunctionof the thought processes and sometimes evencauses abnormal behavioral activities.

30. We are all familiar with the increased sluggishnessof thought that occurs toward the end of a prolongedwakeful period, but in addition, a person can becomeirritable or even psychotic after forced wakefulness. Therefore, we can assume that sleep in multiple waysrestores both normal levels of brain activity andnormal “balance” among the different functions of thecentral nervous system. This might be likened to the“rezeroing” of electronic analog computers after prolongeduse, because computers of this type graduallylose their “baseline” of operation; it is reasonable toassume that the same effect occurs in the centralnervous system because overuse of some brain areasduring wakefulness could easily throw these areas out of balance with the remainder of the nervous system.We might postulate that the principal value of sleepis to restore natural balances among the neuronalcenters. The specific physiologic functions of sleepremain a mystery, and they are the subject of muchresearch.

31. Changes in the EEG at Different Stages of Wakefulness and Sleep Alert wakefulnessis characterized by high-frequency beta waves,whereas quiet wakefulness is usually associated withalpha waves, as demonstrated by the first two EEGs ofthe figure.Slow-wave sleep is divided into four stages. In the firststage, a stage of very light sleep, the voltage of the EEGwaves becomes very low; this is broken by “sleep spindles,”that is, short spindle-shaped bursts of alpha wavesthat occur periodically. In stages 2, 3, and 4 of slow-wavesleep, the frequency of the EEG becomes progressivelyslower until it reaches a frequency of only 1 to 3 wavesper second in stage 4; these are delta waves.It is often difficult to tell thedifference between this brain wave pattern and that ofan awake, active person. The waves are irregular andhigh-frequency, which are normally suggestive of desynchronizednervous activity as found in the awake state. Therefore, REM sleep is frequently called desynchronizedsleep because there is lack of synchrony in thefiring of the neurons, despite significant brain activity.

32. Epilepsy Epilepsy (also called “seizures”) is characterized by uncontrolled excessive activity of either part or all of the central nervous system. A person who is predisposed to epilepsy has attacks when the basal level of excitability of the nervous system (or of the part that is susceptible to the epileptic state) rises above a certain critical threshold. As long as the degree of excitability is held below this threshold, no attack occurs. Epilepsy can be classified into three major types: grand mal epilepsy, petit mal epilepsy, and focal epilepsy.

33. Grand Mal Epilepsy Grand mal epilepsy is characterized by extreme neuronal discharges in all areas of the brain—in the cerebral cortex, in the deeper parts of the cerebrum, and even in the brain stem. Also, discharges transmitted all the way into the spinal cord sometimes cause generalized tonic seizures of the entire body, followed toward the end of the attack by alternating tonic and spasmodic muscle contractions called tonic-clonic seizures. Often the person bites or “swallows” his or her tongue and may have difficulty breathing, sometimes to the extent that cyanosis occurs.Also, signals transmitted from the

34. brain to the viscera frequently cause urination and defecation.The usual grand mal seizure lasts from a few secondsto 3 to 4 minutes. It is also characterized by postseizuredepression of the entire nervous system; the personremains in stupor for 1 to many minutes after theseizure attack is over, and then often remains severelyfatigued and asleep for hours thereafter.The top recording of Figure 59–5 shows a typicalEEG from almost any region of the cortex during thetonic phase of a grand mal attack. This demonstratesthat high-voltage, high-frequency discharges occur overthe entire cortex. Furthermore, the same type of dischargeoccurs on both sides of the brain at the sametime, demonstrating that the abnormal neuronal circuitryresponsible for the attack strongly involves thebasal regions of the brain that drive the two halves ofthe cerebrum simultaneously. In laboratory animals and even in human beings,grand mal attacks can be initiated by administering aneuronal stimulant such as the drug pentylenetetrazol,or they can be caused by insulin hypoglycemia, or bypassage of alternating electrical current directly throughthe brain. Electrical recordings from the thalamus aswell as from the reticular formation of the brain stemduring the grand mal attack show typical high-voltageactivity in both of these areas similar to that recordedfrom the cerebral cortex. Presumably, therefore, a grandmal attack involves not only abnormal activation of thethalamus and cerebral cortex but also abnormal activationin the subthalamic brain stem portions of the brainactivating system itself.

35. What Initiates a Grand Mal Attack? Most people who havegrand mal attacks have hereditary predisposition toepilepsy, a predisposition that occurs in about 1 of every50 to 100 persons. In such people, factors that canincrease the excitability of the abnormal “epileptogenic”circuitry enough to precipitate attacks include (1) strong emotional stimuli, (2) alkalosis caused byoverbreathing, (3) drugs, (4) fever, and (5) loud noisesor flashing lights.

36. Even in people who are not genetically predisposed,certain types of traumatic lesions in almost any part ofthe brain can cause excess excitability of local brainareas, as we discuss shortly; these, too, sometimes transmitsignals into the activating systems of the brain toelicit grand mal seizures. What Stops the Grand Mal Attack? The cause of the extremeneuronal overactivity during a grand mal attack is presumedto be massive simultaneous activation of manyreverberating neuronal pathways throughout the brain. Presumably, the major factor that stops the attack aftera few minutes is neuronal fatigue. A second factor isprobably active inhibition by inhibitory neurons thathave been activated by the attack.

37. Petit Mal Epilepsy Petit mal epilepsy almost certainly involves the thalamocorticalbrain activating system. It is usually characterizedby 3 to 30 seconds of unconsciousness (ordiminished consciousness) during which time theperson has twitch-like contractions of muscles usually inthe head region, especially blinking of the eyes; this isfollowed by return of consciousness and resumption ofprevious activities. This total sequence is called theabsence syndrome or absence epilepsy. it resultsfrom oscillation of (1) inhibitory thalamic reticularneurons (which are inhibitory gamma-aminobutyricacid [GABA]–producing neurons) and (2) Excitatorythalamocortical and corticothalamic neurons.

38. Focal Epilepsy localizedorganic lesion or functional abnormality, such as • scartissue in the brain that pulls on the adjacent neuronaltissue, • a tumor that compresses an area of the brain, • a destroyed area of brain tissue, or • congenitallyderanged local circuitry. When such a wave of excitation spreads over themotor cortex, it causes progressive “march” of muscle contractions throughout the opposite side of the body,beginning most characteristically in the mouth regionand marching progressively downward to the legs but atother times marching in the opposite direction. This iscalled jacksonian epilepsy.

39. Psychotic Behavior andDementia—Roles of SpecificNeurotransmitter Systems Parkinson’sdisease. This disease results from loss of neurons in thesubstantia nigra whose nerve endings secrete dopaminein the caudate nucleus and putamen. Huntington’s disease, loss ofGABA-secreting neurons and acetylcholine-secretingneurons is associated with specific abnormal motor patternsplus dementia occurring in the same patient.

40. Depression and Manic-Depressive Psychoses—Decreased Activity of the Norepinephrine and SerotoninNeurotransmitter Systems Much evidence has accumulated suggesting that mentaldepression psychosis, might be caused by diminishedformation in the brain of norepinephrine or serotonin,or both. Depressed patients experiencesymptoms of grief, unhappiness, despair, and misery. In addition, they often lose their appetite and sexdrive and have severe insomnia. Often associated withthese is a state of psychomotor agitation despite thedepression.

41. Schizophrenia—PossibleExaggerated Function of Part of theDopamine System Schizophrenia comes in many varieties. One of the most common types is seen in the person who hears voices and has delusions of grandeur, intense fear, or other types of feelings that are unreal. Many schizophrenics (1) are highly paranoid, with a sense of persecution from outside sources; (2) may develop incoherent speech, dissociationof ideas, and abnormal sequences of thought;and (3) are often withdrawn, sometimes with abnormalposture and even rigidity.

42. There are reasons to believe that schizophreniaresults from one or more of three possibilities: (1) multipleareas in the cerebral cortex prefrontal lobes inwhich neural signals have become blocked or whereprocessing of the signals becomes dysfunctional becausemany synapses normally excited by the neurotransmitterglutamate lose their responsiveness to this transmitter; (2) excessive excitement of a group of neurons thatsecrete dopamine in the behavioral centers of the brain,including in the frontal lobes; and/or (3) abnormal functionof a crucial part of the brain’s limbic behavioralcontrol system centered around the hippocampus. The reason for believing that the prefrontal lobes areinvolved in schizophrenia is that a schizophrenic-likepattern of mental activity can be induced in monkeys bymaking multiple minute lesions in widespread areas ofthe prefrontal lobes. Dopamine has been implicated as a possible cause ofschizophrenia because many patients with Parkinson’sdisease develop schizophrenic-like symptoms whenthey are treated with the drug called L-dopa. This drugreleases dopamine in the brain, which is advantageousfor treating Parkinson’s disease, but at the same time itdepresses various portions of the prefrontal lobes andother related areas

43. It has been suggested that in schizophrenia excessdopamine is secreted by a group of dopamine-secretingneurons whose cell bodies lie in the ventral tegmentumof the mesencephalon, medial and superior to the substantianigra. These neurons give rise to the so-calledmesolimbic dopaminergic system that projects nervefibers and dopamine secretion into the medial and anteriorportions of the limbic system, especially into thehippocampus, amygdala, anterior caudate nucleus, andportions of the prefrontal lobes. All of these are powerfulbehavioral control centers. An even more compelling reason for believing thatschizophrenia might be caused by excess production ofdopamine is that many drugs that are effective in treatingschizophrenia—such as chlorpromazine, haloperidol,and thiothixene—-all either decrease secretion ofdopamine at dopaminergic nerve endings or decreasethe effect of dopamine on subsequent neurons. Finally, possible involvement of the hippocampus inschizophrenia was discovered recently when it waslearned that in schizophrenia, the hippocampus is oftenreduced in size, especially in the dominant hemisphere.

44. Alzheimer’s Disease—AmyloidPlaques and Depressed Memory Alzheimer’s disease is defined as premature aging of thebrain, usually beginning in mid-adult life and progressingrapidly to extreme loss of mental powers—similarto that seen in very, very old age. The clinical features of Alzheimer’s disease include • an amnesic type ofmemory impairment, • deterioration of language, and (3) visuospatial deficits. Motor and sensory abnormalities,gait disturbances, and seizures are uncommon untilthe late phases of the disease. One consistent finding in Alzheimer’s disease is loss of neurons in that part of thelimbic pathway that drives the memory process. Loss ofthis memory function is devastating. Alzheimer’s disease is a progressive and fatal neurodegenerativedisorder that results in impairment ofthe person’s ability to perform activities of daily livingas well as a variety of neuropsychiatric symptoms and

45. behavioral disturbances in the later stages of thedisease. Patients with Alzheimer’s disease usuallyrequire continuous care within a few years after thedisease begins. Alzheimer’s disease is the most common form ofdementia in the elderly and about 5 million people inthe United States are estimated to be afflicted by thisdisorder. The percentage of persons with Alzheimer’sdisease approximately doubles with every five years ofage, with about 1 percent of 60-year-olds and about 30percent of 85-year-olds having the disease.

46. Alzheimer’s Disease Is Associated withAccumulation of BrainBeta-Amyloid Peptide. Pathologically, one finds increasedamounts of beta-amyloid peptide in the brains ofpatients with Alzheimer’s disease.The peptide accumulatesin amyloid plaques, which range in diameter from10 micrometers to several hundred micrometers and arefound in widespread areas of the brain, including in thecerebral cortex, hippocampus, basal ganglia, thalamus,and even the cerebellum. Thus, Alzheimer’s diseaseappears to be a metabolic degenerative disease.A key role for excess accumulation of beta-amyloidpeptide in the pathogenesis of Alzheimer’s disease issuggested by the following observations: • all currentlyknown mutations associated with Alzheimer’sdisease increase the production of beta-amyloidpeptide; • patients with trisomy 21 (Down syndrome)have three copies of the gene for amyloid precursor protein and develop neurological characteristics ofAlzheimer’s disease by midlife; (3) patients who haveabnormality of a gene that controls apolipoprotein E, ablood protein that transports cholesterol to the tissues,have accelerated deposition of amyloid and greatlyincreased risk for Alzheimer’s disease; (4) Transgenicmice that overproduce the human amyloid precursorprotein have learning and memory deficits in associationwith the accumulation of amyloid plaques; and (5)generation of anti-amyloid antibodies in humans withAlzheimer’s disease appears to attenuate the diseaseprocess.

47. Vascular Disorders May Contribute toProgression of Alzheimer’sDisease. There is also accumulating evidence thatcerebrovascular disease caused by hypertension andatherosclerosis may play a role in Alzheimer’s disease. Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and likely contributes to cognitive decline inAlzheimer’s disease. In fact, many of the common riskfactors for cerebrovascular disease, such as hypertension,diabetes, and hyperlipidemia, are also recognizedto greatly increase the risk for developing Alzheimer’sdisease.

48. Beynin Yapısal Olarak İncelenmesi • BT (Bilgisayarlı Tomografi): X-ışınlarıyla beynin ince kesitleri alınır • MRG (Manyetik Rezonans Görüntüleme): Beyin yapısının incelenmesi için kullanılır

49. Bilgisayarlı Tomografi

50. Manyetik Rezonans Görüntüleme (MRG) • Hasta üniform bir manyetik alan içine sokulur ve daha sonra bu alan içinde kısa bir süreyle radyo frekansı uygulanır. • Atom çekirdeklerindeki rezonans(hidrojen atomları) kafa çevresindeki bir algılayıcı bobin ile ölçülür • Farklı yoğunluktaki dokuların 2 mm uzaysal çözünürlüklü bir görüntüsü elde edilir.