NEUROBEHAVIOR (BEHAVIORAL NEUROLOGY) Untuk Kalangan Sendiri Bagian Saraf FK Undip/RSUP Dr Kariadi Semarang FUNGSI LUHUR Fungsi yang menghubungkan struktur otak dengan perilaku manusia, mencakup 5 aspek : 1. Atensi ( perhatian ) 2. Bahasa 3. Memori (daya ingat ) 4. Visuospasial (pengenalan ruang) 5. Fungsi eksekutif (perencanaan, pengorganisasian dan pelaksanaan) Gangguan fungsi luhur : ringan – berat (pikun) The Division of Cognitive and Behavioral Neurology : provides a comprehensive, multidisciplinary approach to the diagnosis and management of patients who have problems with memory, executive functions, attention, language, emotion, or behavior due to disease, injury, or developmental disorders of the central nervous system. Patients receive the highest standard of neurologic, psychiatric, and social work care for the treatment of their conditions. in the assessment and treatment of diverse clinical problems including: - Dementia (e.g., Alzheimer’s disease and related degenerative disorders, vascular dementia, frontotemporal dementia, dementia with parkinsonism) - Cognitive, Emotional, or Behavioral Problems due to Diverse Conditions (e.g., epilepsy, multiple sclerosis, stroke, traumatic brain injury, brain tumor, systemic diseases with central nervous system manifestations) - Developmental Disorders in Adults (e.g., Attention deficit disorder, learning disabilities, mental retardation, autism) Basic brain biology A simplified model of the human brain consists of many parts: - Brain stem, hind brain, mid brain & cerebellum the most ancient parts, connected to the spine, controls movement, breathing and heartbeats. - Limbic system - consisting of many specialist organs including the Hypothalamus, hippocampus -developed in mammals. Some memory functions and generation of emotional responses. - Cerebral cortex - the distinguishing feature of human brains aspects of memory • Frontal . conceptualisation.thinking.sound and speech processing. orientation.movement.visual processing • Parietal .• Each hemisphere of the cortex can further be divided into four lobes: • Occipital . calculation. recognition • Temporal . planning. . . •Discrimination of shapes e. Shared Emotions neurotransmitters Grey Matter White Maatter ratio Positive emotions Higher levels of dopamine more grey-matter (cell bodies) on the left .Some specific differences between the two hemispheres resulted from this and subsequent research. •Skilled movement. •Position. Negative emotions (fearful mournful feelings). •Reading emotions. •Sensations on both side of face. •Expressing emotions. •Hunger. •Pain. •Reading faces. •Sound perceived by both ears. picking out a camouflaged object. •Understanding geometric properties.g. •Analytical time sequence processing. •Music. •Global holistic processing. The right-brain is better at: Left Hemisphere Right Hemisphere Specialities •Copying of designs. Higher levels of norepinephrine More white-matter (longer axons) on right •Language skills. •Understanding of metaphors. . SIRKUIT AMIGDALA ( LINTASAN EMOSI ) dengan bagian Otak lain Hipokampus Striatum ventral. nukleus dorsomedial thalamus . . Melihat kata (tulisan) . Mendengar kata-kata . Berfikir tentang kata-kata . Mengucapkan kata-kata . PATOGENESIS . GAMBARAN fMRI pasien depresi : penurunan aktifitas metabolik daerah prefrontal . GAMBARAN PET Scan : Peningkatan aktifitas amigdala pada orang yang melihat kata-kata ancaman . – Syndrome which refers to progressive decline in intellectual functioning severe enough to interfere with person’s normal daily activities and social relationships.DEMENTIA DEFINITION: – Group of symptoms that can be caused by over 60-70 disorders. (National Institute on Aging-1995 No. 95-3782) . visual-spatial relationships performance of routine tasks language and communication skills abstract thinking ability to learn and carry out mathematical calculations. irreversible declines in memory.Dementia – Marked by progressive. . Dementia Two Types: – Reversible – Irreversible Individuals must have intensive medical physical to rule out reversible types of dementia. . Trauma to Head Infectious Disorders Alcohol.Overview of Alzheimer's Disease) . Toxicity. Arteriosclerosis (Dick-Mulheke. Delirium Emotions (such as depression) and Endocrine Disorders Metabolic Disturbances Eye and Ear Impairments Nutritional Disorders Tumors.Dementia Reversible: – D= – E= – M= – E= – N= – T= – I= –A Drugs. Dementia Irreversible: – – – – – – – Alzheimer’s Lewy Body Dementia Pick’s Disease (Frontotemperal Dementia) Parkinson’s Heady Injury Huntington’s Disease Jacob-Cruzefeldt Disease . . 1997 Baldereschi et al.ETIOLOGI Penyakit Alzheimer Demensia Vaskuler Pseudodemensia Demensia alkoholik Tumor intrakranial NPH Intoksikasi Huntington Penyakit lain 50% 10% 8% 7% 5% 5% 3% 2% 10% Adams RD. 1998 . Kluger A. 1999 .Progression of normal aging to dementia Normal Cognition Brain Aging stable or stable or reversible reversible impairment impairment Prodromal Dementia revers MCI MCI / VCI Dementia other dementia dementia other Alzheimer Alzheimer’s dementia disease vascular vascular dementia dementia Golomb J.Ferris SH. 000 people in U.000. doubles with every decade of life. After age 65 the percentage of affected people. Caring for patient with Alzheimer's disease can cost $47.000 per year (NIH). Estimated that 25-35% of people over age 85 have some time of dementia.•Alzheimer's Disease Estimated that 4. .S. have Alzheimer's disease. and brain stem .Changes Caused by Alzheimer's Diminished blood flow Neurofibrillary Tangles Neuritic Plaques Degeneration of hippocampus. cerebral cortex. hypothalamus. . . Genetic Theories ApoE4 on chromosone 19 linked to late-onset Alzheimer’s Disease.Theories Regarding Causes of Alzheimer's Changes in Neurotransmitters Acetycholine is decreased--necessary for cognitive functioning. . Changes in Protein Synthesis Beta amyloid--may be responsible for forming plaques. Tau--major component of neurofibrillary tangles. Theories Regarding Causes of Alzheimer's Genetic Theories Chromosome 21 --Responsible for early-onset Alzheimer’s Disease. Suspect that it may reason why neurons die in Alzheimer's patients. Calcium Theories Too much calcium can kill cells. Metabolic Theories Glucose metabolism declines dramatically in Alzheimer’s patients. . (NIH-1995) . Viral May be hidden in body and attack brain cells years later. Food borne poisons--amino acids found in legumes in Africa and India my cause neurological damage.Theories Regarding Causes of Alzheimer's Environmental Aluminum--Traces of metal found in brain. Zinc--found in brains on autopsies. Theories Regarding Causes of Alzheimer's Head Trauma – Head trauma increase the concentration of B-amyloid protein Low Level of Education – Individuals with low level of education less able to compensate for cognitive deficits Estrogen Deficiency Early Life Experience---have lost parent before age 16 . and amygdala.The Cholinergic Hypothesis Acetylcholine is as important neurotransmitter in areas of the brain involved in memory formation – the hippocampus. . cerebral cortex. Enhancement or restoration of cholinergic function may significantly reduce the severity of cognitive loss. Concentrations of acetylcholine are markedly decreased in Alzheimer’s disease. Depletion is limited to the basal forebrain projection system. Gauthier at all. 1997 . Neuronal Degeneration The pathobiology of Alzheimer’s disease is characterized by: Amyloid plaques Neurofibrillary tangles . Remains of damaged neuronal microtubules. . Filaments appear to be composed of a hyperphosphorylated microtubuleassociated protein called tau.Neurofibrillary Tangles Intracellular inclusion bodies consisting of paired helical filaments that appear in a characteristic double-helix shape. Plaques consist of a central core of betaamyloid protein surrounded by abnormal axons and dendrites. particularly in the hippocampus and neocortex. Amyloid (neuritic) plaques in Alzheimer’s disease are dense and insoluble structures.Amyloid Plaques Plaques are extracellular structures that are more prevalent in the Alzheimer’s patient’s brain. . Diagnosis of Dementia Due to Alzheimer’s Memory Impairment Multiple cognitive deficits with at least one disturbance in the following areas: – Aphasia—loss of the ability to use symbols to communicate orally or in writing Two Types: – Expressive—inability to form words – Receptive—decreased ability to understand spoken or written language – Apraxia—inability to initiate complex learned motor movement or unable to perform activity on command – Agnosia---inability to recognize familiar objects by sight. touch. taste. smell or sound . atrophy of brain (CT or MRI) Blood Work .Diagnostic Tests Neurological Exam Brain Imaging—shrinkage. . Anthony JC. 18 : 2386-91 . Folstein MF.Median Scores on Mini-Mental State Examination by Age and Educational Level Age (years) 4th grade 18 to 24 25 to 29 30 to 34 35 to 39 40 to 44 45 to 49 50 to 54 55 to 59 60 to 64 65 to 69 70 to 74 75 to 79 80 to 84 > 84 22 25 25 23 23 23 23 23 23 22 22 21 20 19 27 27 26 26 27 26 27 26 26 26 25 25 25 23 Educational level 8th grade High school 29 29 29 28 28 28 28 28 28 28 27 27 25 26 College 29 29 29 29 29 29 29 29 29 29 28 28 27 27 Reprinted with permisssion from Crum RM. Basset SS. Population-based norms for the mini-mental state examination by age and educational level. JAMA 1993 . . . Paying Bills .Stages of Alzheimer’s Disease Mild Stage – Memory Loss – Symptoms: Confusion About Place Loss of Spontaneity Loss of Initiative Mood/Personality Changes Poor Judgment Takes Longer to Perform Routine chores Trouble Handling Money. Stages of Alzheimer’s Disease Moderate Stage Impairments in: language motor ability object recognition increasing memory loss and confusion . Perceptual motor problems. close friends.Stages of Alzheimer’s Disease Moderate Stage – Symptoms: Problems recognizing family members. especially in late afternoon and at night. irritable. Problems organizing thoughts. fidgety. Repetitive statements and/or movements. makes up stories. Restless. Occasional muscle twitches or jerking. thinking logically. teary or silly. May be suspicious. Problems reading and writing. . Can’t find right words. May put everything in mouth or touch everything. skin breakdown. May have difficult with seizures. Can’t communicate with words. . Can’t control bladder or bowel. infections.Stages of Alzheimer’s Disease Severe Stage – Symptoms: Loses weight even with good diet. Little capacity for self-care. swallowing. Loss of ability to hold up head. Loss of ability to swallow. .Stages of Alzheimer’s Disease Terminal Stage – Symptoms: Loss of ability to ambulate. Loss of ability to sit. Loss of ability to smile. Hurley. Loss of ability to swallow. Md . Loss of ability to sit. Management of Challenging Behaviors in Dementia—Mahoney. .Stages of Alzheimer’s Disease Stage IV--Terminal Stage – Symptoms: Loss of ability to ambulate. Loss of ability to smile. Loss of ability to hold up head. Health Professionals Press:2000. Volicer. Baltimore. rivastigmine) ?Vitamin E 2000 IU units per day .Potential agents that can be of benefit for Alzheimer’s disease Reversible inhibitors of the enzyme acetylcholinesterase (donepezil.4 month delay in disease progression ?Gingko biloba – 40 mg tid . tacrine.6 month delay in disease progression ?Selegiline 5 mg twice a day . . . THANKS FOR YOUR ATTENTION .