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Untuk Kalangan Sendiri Bagian Saraf FK Undip/RSUP Dr Kariadi Semarang

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., Alzheimers 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

Each hemisphere of the cortex can further be divided into four lobes: Occipital - visual processing Parietal - movement, orientation, calculation, recognition Temporal - sound and speech processing, aspects of memory Frontal - thinking, conceptualisation, planning.

Some specific differences between the two hemispheres resulted from this and subsequent research. The right-brain is better at:
Left Hemisphere Right Hemisphere


Copying of designs, Discrimination of shapes e.g. picking out a camouflaged object, Understanding geometric properties, Reading faces, Music, Global holistic processing, Understanding of metaphors, Expressing emotions, Reading emotions. Sensations on both side of face, Sound perceived by both ears, Pain, Hunger, Position. Negative emotions (fearful mournful feelings), Higher levels of norepinephrine More white-matter (longer axons) on right

Language skills, Skilled movement, Analytical time sequence processing.


Emotions neurotransmitters Grey Matter White Maatter ratio

Positive emotions Higher levels of dopamine more grey-matter (cell bodies) on the left

( LINTASAN EMOSI ) dengan bagian Otak lain


Striatum ventral, nukleus dorsomedial thalamus

Melihat kata (tulisan)

Mendengar kata-kata

Berfikir tentang kata-kata

Mengucapkan kata-kata


GAMBARAN fMRI pasien depresi : penurunan aktifitas metabolik daerah prefrontal

GAMBARAN PET Scan : Peningkatan aktifitas amigdala pada orang yang melihat kata-kata ancaman

Group of symptoms that can be caused by over 60-70 disorders. Syndrome which refers to progressive decline in intellectual functioning severe enough to interfere with persons normal daily activities and social relationships. (National
Institute on Aging-1995 No. 95-3782)

Marked by progressive, irreversible declines in
memory. visual-spatial relationships performance of routine tasks language and communication skills abstract thinking ability to learn and carry out mathematical calculations.

Two Types:
Reversible Irreversible

Individuals must have intensive medical physical to rule out reversible types of dementia.

D= E= M= E= N= T= I= A Drugs, Delirium Emotions (such as depression) and Endocrine Disorders Metabolic Disturbances Eye and Ear Impairments Nutritional Disorders Tumors, Toxicity, Trauma to Head Infectious Disorders Alcohol, Arteriosclerosis (Dick-Mulheke- Overview of
Alzheimer's Disease)

Alzheimers Lewy Body Dementia Picks Disease (Frontotemperal Dementia) Parkinsons Heady Injury Huntingtons Disease Jacob-Cruzefeldt Disease

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, 1997

Baldereschi et al., 1998

Progression of normal aging to dementia

Normal Cognition

Brain Aging
stable or stable or reversible reversible impairment impairment

Prodromal Dementia




other dementia dementia


Alzheimer Alzheimers dementia disease

vascular vascular dementia dementia

Golomb J,Kluger A,Ferris SH, 1999

Alzheimer's Disease
Estimated that 4,000,000 people in U.S. have Alzheimer's disease. Estimated that 25-35% of people over age 85 have some time of dementia. After age 65 the percentage of affected people, doubles with every decade of life. Caring for patient with Alzheimer's disease can cost $47,000 per year (NIH).

Changes Caused by Alzheimer's

Diminished blood flow Neurofibrillary Tangles Neuritic Plaques Degeneration of hippocampus, cerebral cortex, hypothalamus, and brain stem

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.

Genetic Theories
ApoE4 on chromosone 19 linked to late-onset Alzheimers Disease.

Theories Regarding Causes of Alzheimer's

Genetic Theories
Chromosome 21 --Responsible for early-onset Alzheimers Disease.

Metabolic Theories
Glucose metabolism declines dramatically in Alzheimers patients.

Calcium Theories
Too much calcium can kill cells. Suspect that it may reason why neurons die in Alzheimer's patients.

Theories Regarding Causes of Alzheimer's

Aluminum--Traces of metal found in brain. Zinc--found in brains on autopsies. Food borne poisons--amino acids found in legumes in Africa and India my cause neurological damage.

May be hidden in body and attack brain cells years later. (NIH-1995)

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

The Cholinergic Hypothesis

Acetylcholine is as important neurotransmitter in areas of the brain involved in memory formation the hippocampus, cerebral cortex, and amygdala. Concentrations of acetylcholine are markedly decreased in Alzheimers disease. Enhancement or restoration of cholinergic function may significantly reduce the severity of cognitive loss. Depletion is limited to the basal forebrain projection system.

Gauthier at all, 1997

Neuronal Degeneration
The pathobiology of Alzheimers disease is characterized by: Amyloid plaques Neurofibrillary tangles

Neurofibrillary Tangles
Intracellular inclusion bodies consisting of paired helical filaments that appear in a characteristic double-helix shape. Filaments appear to be composed of a hyperphosphorylated microtubuleassociated protein called tau. Remains of damaged neuronal microtubules.

Amyloid Plaques
Plaques are extracellular structures that are more prevalent in the Alzheimers patients brain, particularly in the hippocampus and neocortex. Amyloid (neuritic) plaques in Alzheimers disease are dense and insoluble structures. Plaques consist of a central core of betaamyloid protein surrounded by abnormal axons and dendrites.

Diagnosis of Dementia Due to Alzheimers

Memory Impairment Multiple cognitive deficits with at least one disturbance in the following areas:
Aphasialoss of the ability to use symbols to communicate orally or in writing
Two Types:
Expressiveinability to form words Receptivedecreased ability to understand spoken or written language

Apraxiainability 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

Diagnostic Tests
Neurological Exam Brain Imagingshrinkage, atrophy of brain (CT or MRI) Blood Work

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, Anthony JC, Basset SS, Folstein MF. Population-based norms for the mini-mental state examination by age and educational level. JAMA 1993 ; 18 : 2386-91

Stages of Alzheimers 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, Paying Bills

Stages of Alzheimers Disease

Moderate Stage
Impairments in:
language motor ability object recognition increasing memory loss and confusion

Stages of Alzheimers Disease

Moderate Stage
Symptoms: Problems recognizing family members, close friends.
Repetitive statements and/or movements. Restless, especially in late afternoon and at night. Occasional muscle twitches or jerking. Perceptual motor problems. Problems organizing thoughts, thinking logically. Cant find right words, makes up stories. Problems reading and writing. May be suspicious, irritable, fidgety, teary or silly.

Stages of Alzheimers Disease

Severe Stage
Loses weight even with good diet. Little capacity for self-care. Cant communicate with words. May put everything in mouth or touch everything. Cant control bladder or bowel. May have difficult with seizures, swallowing, skin breakdown, infections.

Stages of Alzheimers Disease

Terminal Stage
Loss of ability to ambulate. Loss of ability to sit. Loss of ability to smile. Loss of ability to hold up head. Loss of ability to swallow.

Stages of Alzheimers Disease

Stage IV--Terminal Stage
Loss of ability to ambulate. Loss of ability to sit. Loss of ability to smile. Loss of ability to hold up head. Loss of ability to swallow.
Management of Challenging Behaviors in DementiaMahoney, Volicer, Hurley. Health Professionals Press:2000. Baltimore, Md

Potential agents that can be of benefit for Alzheimers disease

Reversible inhibitors of the enzyme acetylcholinesterase (donepezil, tacrine, rivastigmine) ?Vitamin E 2000 IU units per day - 6 month delay in disease progression ?Selegiline 5 mg twice a day - 4 month delay in disease progression ?Gingko biloba 40 mg tid