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Neurodegenerative diseases Neurodegeneration: progressive loss of structure or function of neurons, including death of neurons. Many diseases such as Parkinson’s,

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Presentation on theme: "Neurodegenerative diseases Neurodegeneration: progressive loss of structure or function of neurons, including death of neurons. Many diseases such as Parkinson’s,"— Presentation transcript:

1 Neurodegenerative diseases Neurodegeneration: progressive loss of structure or function of neurons, including death of neurons. Many diseases such as Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. Recent insights put MS on the map of neurodegenerative disease. As research progresses, many similarities appear which relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

2 Neurodegenerative diseases Systemic level: similarities in terms of localization Cortical Function – Basal ganglia -

3 Primary Sensori-motor Areas Frontal lobe Behavioral Planning Working Memory Affective Processing Attention Higher Functions

4 MINI MENTAL STATE EXAMINATION Section 1: Orientation Section 2: Memory (part 1) Section 3: Attention and calculation Section 4: Memory (recall- part 2) Section 5: Language, writing and drawing General testing of cognitive functions

5 MINI MENTAL STATE EXAMINATION Section 1: Orientation The first 10 points are gained for giving the correct date and location. Section 2: Memory (part 1) The first part of the memory test tests the ability to remember immediately three words. You will be given the names of three objects to remember - table, ball and pen, for example. You will then be asked to repeat the three names, scoring 1 point for each object correctly recalled (3 points maximum). You should try to remember the three items as you will be asked to recall them later in the test. Section 3: Attention and calculation The next part of the MMSE tests the ability to concentrate on a tricky task. Two different tests are used, and the best of the two scores is included in the final score. You will be asked to count backwards. For example, start at 50 and count backwards by 5. One point is given for each correct subtraction, with a maximum of 5 points. You may also be asked to spell a word backwards such as 'lunch'. Again, the maximum score is 5.

6 MINI MENTAL STATE EXAMINATION Section 4: Memory (part 2) You will now be asked to recall the three items from Section 2. One point is given for each correctly recalled object. Sometimes the person doing the testing will drop hints! Section 5: Language, writing and drawing The final part of the test makes an assessment of spoken and written language, and the ability to write and copy. The person being tested is shown two everyday items - a hammer and a crayon, for example - and asked to name them. You score 1 point for each correct answer. You will then be asked to say aloud a tongue-twister sentence such as 'Pass the peas please'. Correctly repeating the sentence gains 1 point. The sentence is always the same, so is worth practising once you have heard it the first time. You will then be given a piece of paper, and asked to carry out a three-step process: 'Take this paper in your hand' (1 point); 'Fold it in half' (1 point); 'Place it on this chair' (1 point). The instruction is given only once, but as with the tongue-twister, the task is always the same.

7 MINI MENTAL STATE EXAMINATION Section 5: Language, writing and drawing (continuation) A card is then shown with an instruction for a simple task - 'Clap your hands'. If you clap your hands you score 1 point. The next stage of the test is to write a sentence on a piece of paper. The sentence needs to make sense. One point is scored for an acceptable sentence. Examples of acceptable sentences include: 'It's a lovely day today.' 'My name is Roger.' Finally, your ability to copy a design of two intersecting shapes is assessed. One point is awarded for correctly copying it. All angles on both figures must be present, and the figures must have one overlapping angle. This is the end of the test.

8 Frontal lobe Behavioral Planning Working Memory Affective Processing Attention (Restraint, Initiative, Order -RIO) Frontal Lobes Largest region of the brain (1/3 of the cortex) Lateral, medial, orbitofrontal surfaces Parietal Occipital Temporal Limbic ->ACC) Amigdala Hippocampus thalamus (MD nucleus) Head of Caudate Cerebellum Hypothalamus, braistem

9 Functions of Frontal Association Cortex + Motor and Behavioral Planning (perseverations) + Speech Production + Working memory & attention (dual task) + Suppression of Stimulus-bound behavior babies & demented people cannot suppress urge to urinate in response to a full bladder + Inappropriate social behavior (frontal release) + Affective Processing (Abulia) + Complex task solving Frontal function must be studied with complex paradigms (delayed response, Towers, Stroop, WCST)

10 Signs of Frontal Damage Emergence of primitive reflexes, impossible to suppress: Grasp reflex Suck reflex snout reflex Perseveration (repetition of one behavior without strategy changing) Failure to suppress inappropriate responses to sensory stimuli: Antisaccade Failure to suppress blink in response to glabellar tap Motor signs: Motor impersistence Paratonia Magnetic gait

11 Frontal Lobe Disorders Vascular Tumors Abscess Frontal Lobe degeneration (Pick’s disease) Seizures Toxic, metabolic Demyelination (MS) AD, PD, HD Schizophrenia Depression

12 Delayed Response Paradigm

13 Wisconsin Card Sorting Test Tower Tests

14 Other Frontal lobe Tests: Cognitive Estimate testing Digit Span Trail Making test Verbal fluency Abstraction Movement coordination

15 Functions of Parietal Cortex - Attention - Spatial location - Body image - Multi-sensory integration - Transfer of sensory information to the motor system

16 Hemineglect : Deficits of spatial attention following Right parietal lesions  Inability to attend objects or their own body parts in the left space  Visual acuity normal  Somatic sensation normal  Motor ability generally preserved, although complex motor behavior can be abnormal in the left space  Association with anosognosia (denial of illness), anosodiaphoria (absence of emotional distress for the deficits), hemisomatoanognosia (denial of the affected part- ”somebody left an arm in my bed”)  Sensory, motor, sensory-motor and conceptual neglect



19 Severe L hnMinimal R hnSevere R hn Hemineglect : A prominent role role of the Right parietal cortex Anatomical evidence

20 Hemineglect : Improvement: Neglect improves following L caloric vestibular stimulation, and worsens following R vestibular stimulation. No modification of neglect is observed after bilateral vestibular stimulation. Caloric vestibular stimulation may improve neglect through a specific effect; bilateral stimulation making the putative activation bilateral and symmetrical does not affect the lateral bias of neglect.

21 Parietal Cortex: Apraxia

22 Parietal Cortex Disorders Gerstmann’s Syndrome 1.Agraphia 2.Acalculia 3.Right-left disorientation 4.Finger agnosia 5.No confusion If all symptoms are present -->dominant (left) inferior parietal lobe (angular gyrus) Balint’s Syndrome 1.Simultanagnosia (impaired ability to perceive a scene as a whole: deficit in visuospatial binding) 2.Optic ataxia (inability to reach/point under visual guidance; dd: cerebellar ataxia) 3.Ocular apraxia (difficulty in directing gaze to peripheral visual field; use of head movements) -->bilateral lesions of the dorsolateral parieto-occipital cortex

23 Temporal Cortex Agnosias: Inability to recognize “what”… Objects Faces: prosopagnosia Language problems WHERE WHAT PARIETAL DORSAL STREAM TEMPORAL VENTRAL STREAM Retina LGNd Pulvinar


25 MEMORY TESTS Wechsler Memory Scale: The task is to recall stories and other verbal stimuli. The test is appropriate for people with ages of 16-74. VERBAL MEMORY TESTS (presentation of words, digits, nonsense syllables, sentences that must then be recalled : California Verbal Learning Test. Rey Auditory Verbal Learning Test. Selective Reminding Test. NON-VERBAL MEMORY TESTS (ability to perceive and retain images of visually presented geometric figures): Benton Test of Visual Retention-Revised. Memory for Designs Test. Rey-O Complex Figure More "ecologically valid", or "real world" in nature, using tasks that people must perform each day such as remembering names and faces when meeting new people or lists.


27 NO BRAIN AREA IS AN ISLAND Functional connectivity

28 Frontal lobe Dysfunctions Either side: a.Contralateral hemiplegia b.Euphoria, talkativeness, tendency to joke,lack of tact, loss of initiative c.Grasp & suck reflex d.Incontinence e.impaired planning & execution of complex action sequences f.perseverations Right: a.gross social impairment (loss of insight, dysinhibition, loss of respect for others, personality changes) Left: a.Aphasia (non-fluent, Broca type) b.Agraphia, possibly with lips and tongue apraxia c.Apraxia of the left hand Bilateral: a.Pseudobulbar palsy (shuffled gait, precarious balance, apraxia of gait, bent posture) b.Abulia, akinetic mutism, inability to: sustain attention, solve problems; rigid thinking, bland affect, labile mood

29 Occipital lobe Either side a.Contralateral homonymous hemianopia (color loss) b.Unformed allucinations (elementary) Left (dominant) a.Right homonymous hemianopia b.Alexia, color naming problem (splenium, white matter) c.Visual object agnosia d.Astereognosia Right: a.Left homonymous hemianopia b.Rarely, visual illusion & allucinations c.Loss of topographic memory & visual orientation Bilateral: a.Cortical blindness, b.Denial of cortical blindness (Anton’s Syndrome) c.Achromatopsia d.Prosapagnosia, simultanagnosia e.Balint syndrome (inability to: scan peripheral space- intact eye movs-; grasp -optic ataxia hand/eye incoord.-; vissual inattention)

30 Parietal lobe Either side a.Contralateral sensory syndrome, sensory extinction b.Mild contralateral hemiparesis, hemiataxia c.Visual defects Left (dominant) a.Aphasia (fluent, conduction aphasia: lesions of inferior parietal lobe- supramarginal gyrus) b.Gerstmann syndrome (R-L body confusion; finger agnosia- name/designate fingers; dysgraphia; dyscalculia) c.Apraxia d.Astereognosia Right: a.Hemineglect b.Topographic memory loss, visuo-spatial disorders c.Anosognosia ( denial of L hemiparesis, also for frontal, temporal & subcortical lesions), dressing & constructional apraxia d.Confusion, tendency to keep eyes closed Bilateral: a.Neglect, b.Visuo-spatial dysperception and disorientation

31 Temporal lobe Either side Memory problems, declarative, spatial, including retrieval, formation of new long-term memories a.Auditory, visual, olfactory, gustatory allucinations b.Aggressive, psychotic behavior, emotional changes c.Time misperception Left (dominant) a.Homonimous upper quadrantopia b.Aphasia (fluent, confabulations, Wernicke’s type) c.Amusia d.Impaired comprehension of auditory-presented material e.Visual agnosia; impaired object perception & recognition Right: a.Homonimous upper quadrantopia b.Impaired judgment of spatial relations c.Impaired comprehension of visual nonverbal material d.Agnosia for sounds & some music characteristics Bilateral: a.Sham rage b.Korsakoff syndrome c.Apathy & placidityKluver-Bucy d.Hypersexuality, hyperorality bulimiasyndrome

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