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M. Alzheimer

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Title: M. Alzheimer


1
M. Alzheimer
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Etiopatogenesis patological proteins
  • neuritic plaques
  • ? amyloid
  • amyloid precursor protein (APP)
  • ? sekretase
    ? sekretase
  • ? amyloid
    ? APP
  • plaques
    transduction

4
Etiopatogenesis patological proteins
  • Neurofibrillar tangles
  • tau protein
  • in CNS stabilization of microtubullar network
  • AD - abnormal fosforylation
  • - shortened of tau protein
  • Is not able to make connection with mikrotubulles
  • Interactions with other proteins ? hellical
    fibers ? degeneration of neurons ? apoptosis

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Etiopatogenesisbrain atrophy
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EtiopatogenesisACh deficit
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Etiopatogenesis inflammation
Alzheimer - reactive astrocytes, microglia
activated microglial cells
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Etiopatogenesis genetic factors
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New criteria for AD diagnosis
  1. Impairment of episodic memory
  2. Atrophy of medial temporal structures on MRI
  3. Abnormal cerebrospinal fluid markers
  4. Specific metabolic pattern evidenced with
    molecular neuroimaging methods
  5. Familial genetic mutations

Dubois a kol., 2007
10
Memory
  • Epizodic memory significantly impaired
    episodic memory - for recalling informations from
    memory, it needs personal experience

11
Clinical criteria AD
  • Failure of short episodic memory and its
    recolling (hippocampal atrophy, do not save
    information, ? no benefit of helping to patient)
  • Failure of visuospatial orientation
  • Failure of executive functions (such as
    planning, working memory, attention, problem
    solving, verbal reasoning, inhibition, mental
    flexibility, multi-tasking, initiation and
    monitoring of actions)

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Clinical criteria AD
  • Deterioration of fatic, gnostic functions and
    praxia
  • Apathy, agresivity, anxiety, depression

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B. Atrophy of medial temporal structures on MRI
  • Common in AD 71 96
  • Frequent in MCI 59 78
  • Less frequent in normal ageing 29
  • Sensitivity and specificity more than 85

Dubois a kol., 2007
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Medial temporal structures on MRI
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Medial temporal structures on MRI
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MRI - hippocampus
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MRI - hippocampus
Alzheimer disease
Normal MRI
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C. Abnormal cerebrospinal fluid biomarkers
  • Amyloid ?42 - A ?42 - ?
  • Total tau protein t-tau - ?
  • Phospho-tau protein p-tau - ?

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D. Specific metabolic pattern evidenced with
molecular neuroimaging methods (PET)
  • With 18F-FDG PET (F fluoro-2-deoxyglucosis)
    visualisation of hypometabolism in
    temporoparietal region
  • With PiB PET (PiB-Pittsburg compound) substance
    binding to amyloid and is visible by PET

20
18F-FDG PET
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D. Specific metabolic pattern evidenced with
molecular neuroimaging methods
Rabinovici a kol., 2009
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D. Specific metabolic pattern evidenced with
molecular neuroimaging methods (SPECT)
  • 99mTc-HMPAO SPECT
  • (measure blood flow)
  • in AD. Woman, age 56 , dg. AD, MMSE - 12.
    Transversal brain section rCBF reduction in
    parietal cortex of both hemispheres and in F and
    T cortex in left hemisphere.

Kupka a kol.
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E. Familial genetic mutations
  • Tri autosomal dominant mutations cause AD
  • Chromosome 21 amyloid precursor protein
  • Chromosome 14 presinilin 1
  • Chromsome 1 presenilin 2

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Diagnosis
  • Laboratory tests
  • Blood count, sugar, Na, K, urea, TSH, cholesterol
    (total, LDL, HDL), B12,
  • others

25
Therapy
  • Increasing of cholinergic activity
  • Acetylcholine inhibitors
  • DONEPEZIL (ARICEPT)
  • RIVASTIGMIN (EXELON)
  • GALANTAMIN (REMINYL)

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Therapy
  • Modulators of glutamatergic transmission
  • Memantin blocer of NMDA receptor channels

27
Therapy
  • Behaviour problems
  • Agressivity
  • Insomnia
  • Depression

28
Lewy body dementia
  • Memory loss
  • Parkinson syndrome
  • Visual halucinations
  • Worsening after neuroleptics

29
Frontotemporal lobar degeneration
  • 3rd most often neurodegenerative dementia
  • Starting before age of 65 (35-75)
  • Shorter time of survival
  • Faster progression of cognitive and functional
    deficit

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Frontotemporal lobar degeneration - FTLD
  • 3 types
  • Frontotemporal dementia
  • Primary progressive (non-fluent) aphasia
  • Semantic dementia

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Frontotemporal lobar degeneration - FTLD
  • Early behavioral -dysexecutive syndrom and fatic
    and/or gnostic functions
  • 20-40 - positive family history
  • Dysexecutive syndrome dysfunction in executive
    functions like planning, abstract thinking,
    flexibilty, behaviour control

32
Frontotemporal lobar degeneration - FTLD
  • MRI
  • Atrophy of frontal lobes and anterior part of
    temporal lobes, amygdala, sometimes with
    assymetry
  • Symmetry in frontal dementia
  • Asymetric FT atrophy mainly in left hemisphere
    primary progressive aphasia
  • Bilateral symmetric aphasia T neokortex
    semantic dementia

33
Frontal dementia
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Primary progressive aphasia
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Semantic dementia
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Vascular dementia
  • Dementia
  • - loss of cognitive functions
  • - memory problems
  • Cerebrovascular disease

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Classification of VaD
  1. Multiinfarct dementia (K,S)
  2. Demencia after stroke in strategic localisation
  3. Small vessel disease (K,S)
  4. Hypoperfusion (surgery in older age ? risc
    4-times)
  5. Dementia after brain haemorrhage
  6. Other mechanisms

39
Risk factors of dementia
  • TIA
  • Stroke
  • Arterial hypertension
  • Diabetes mellitus
  • Atrial fibrillation
  • Hyperlipidemia

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VaD vs AD
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Vascular dementia
  • Sudden onset of cognitive decline, fluctuations
  • ! Small vessel disease slow onset, slow
    progression
  • Gait problems and falls
  • Incontinentia in early stages

42
Dg VaD - CT
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Dg. VaD - MRI
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Dg. VaD MRI
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Dg. VaD Ultrasound and AG
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Therapy VaD
  • AChE Inhibitors and memantin ?
  • Stroke prevention
  • ASA, clopidogrel, dipyridamol ASA
  • Anticoagulant th AF
  • Therapy of risk factors
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