M. Alzheimer

1
M. Alzheimer
2
(No Transcript)
3
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

5
Etiopatogenesisbrain atrophy
6
EtiopatogenesisACh deficit
7
Etiopatogenesis inflammation
Alzheimer - reactive astrocytes, microglia
activated microglial cells
8
Etiopatogenesis genetic factors
9
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)

12
Clinical criteria AD

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

13
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
14
Medial temporal structures on MRI
15
Medial temporal structures on MRI
16
MRI - hippocampus
17
MRI - hippocampus
Alzheimer disease
Normal MRI
18
C. Abnormal cerebrospinal fluid biomarkers

• Amyloid ?42 - A ?42 - ?
• Total tau protein t-tau - ?
• Phospho-tau protein p-tau - ?

19
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
21
D. Specific metabolic pattern evidenced with
molecular neuroimaging methods
Rabinovici a kol., 2009
22
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.
23
E. Familial genetic mutations

• Tri autosomal dominant mutations cause AD
• Chromosome 21 amyloid precursor protein
• Chromosome 14 presinilin 1
• Chromsome 1 presenilin 2

24
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)

26
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

30
Frontotemporal lobar degeneration - FTLD

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

31
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
34
Primary progressive aphasia
35
Semantic dementia
36
Vascular dementia

• Dementia
• - loss of cognitive functions
• - memory problems
• Cerebrovascular disease

37
(No Transcript)
38
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

40
VaD vs AD
41
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
43
Dg. VaD - MRI
44
Dg. VaD MRI
45
Dg. VaD Ultrasound and AG
46
Therapy VaD

• AChE Inhibitors and memantin ?
• Stroke prevention
• ASA, clopidogrel, dipyridamol ASA
• Anticoagulant th AF
• Therapy of risk factors