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.

Neurodegenerative diseases

Systemic level: similarities in terms of localization

Cortical Function –

Basal ganglia -

Primary Sensori-motor Areas

Frontal lobe

Behavioral Planning

Working Memory

Affective Processing

Attention

Higher Functions

MINI MENTAL STATE EXAMINATION

Section 1: OrientationSection 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

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.

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.

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.

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

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)

Signs of Frontal Damage

• Emergence of primitive reflexes, impossible to suppress:Grasp reflexSuck reflexsnout reflex

• Perseveration (repetition of one behavior without strategy changing)• Failure to suppress inappropriate responses to sensory stimuli:

AntisaccadeFailure to suppress blink in response to glabellar tap

• Motor signs:Motor impersistenceParatoniaMagnetic gait

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

Delayed Response Paradigm

Wisconsin Card Sorting Test

Tower Tests

Other Frontal lobe Tests:

Cognitive Estimate testingDigit SpanTrail Making testVerbal fluencyAbstractionMovement coordination

Functions of Parietal Cortex

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

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

Severe L hn Minimal R hn Severe R hn

Hemineglect:

A prominent role role of the Right parietal cortex

Anatomical evidence

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.

Parietal Cortex: Apraxia

Parietal Cortex Disorders

Gerstmann’s Syndrome 1. Agraphia2. Acalculia3. Right-left disorientation4. Finger agnosia5. 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

Temporal Cortex

Agnosias:Inability to recognize “what”…

ObjectsFaces: prosopagnosiaLanguage problems

WHERE

WHAT

PARIETALDORSAL STREAM

TEMPORALVENTRAL STREAM

Retina

LGNd

Pulvinar

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.

NO BRAIN AREA IS AN ISLAND

WHAT

PARIETALDORSAL STREAM

TEMPORALVENTRAL STREAM

Retina

LGNd

Pulvinar

FRONTALCONVERGENCE

Anatomical connectivity

NO BRAIN AREA IS AN ISLAND

Functional connectivity

Frontal lobe Dysfunctions

Either side:a. Contralateral hemiplegiab. Euphoria, talkativeness, tendency to joke,lack of tact, loss of initiativec. Grasp & suck reflexd. Incontinencee. impaired planning & execution of complex action sequencesf. perseverationsRight: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 apraxiac. Apraxia of the left handBilateral: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

Occipital lobe

Either sidea. 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 agnosiad. AstereognosiaRight:a. Left homonymous hemianopiab. Rarely, visual illusion & allucinationsc. Loss of topographic memory & visual orientationBilateral:a. Cortical blindness, b. Denial of cortical blindness (Anton’s Syndrome)c. Achromatopsiad. Prosapagnosia, simultanagnosiae. Balint syndrome (inability to: scan peripheral space- intact eye movs-;

grasp -optic ataxia hand/eye incoord.-; vissual inattention)

Parietal lobe

Either sidea. Contralateral sensory syndrome, sensory extinctionb. Mild contralateral hemiparesis, hemiataxiac. Visual defectsLeft (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. Apraxiad. AstereognosiaRight:a. Hemineglectb. Topographic memory loss, visuo-spatial disordersc. Anosognosia (denial of L hemiparesis, also for frontal, temporal & subcortical lesions),

dressing & constructional apraxiad. Confusion, tendency to keep eyes closedBilateral:• Neglect, • Visuo-spatial dysperception and disorientation

Temporal lobeEither side• Memory problems, declarative, spatial, including retrieval, formation of new

long-term memoriesa. Auditory, visual, olfactory, gustatory allucinationsb. Aggressive, psychotic behavior, emotional changesc. Time misperceptionLeft (dominant)a. Homonimous upper quadrantopiab. Aphasia (fluent, confabulations, Wernicke’s type) c. Amusiad. Impaired comprehension of auditory-presented materiale. Visual agnosia; impaired object perception & recognitionRight:a. Homonimous upper quadrantopiab. Impaired judgment of spatial relationsc. Impaired comprehension of visual nonverbal materiald. Agnosia for sounds & some music characteristicsBilateral:a. Sham rageb. Korsakoff syndromec. Apathy & placidity Kluver-Bucyd. Hypersexuality, hyperorality bulimia syndrome