Title: M. Alzheimer
1M. Alzheimer
2(No Transcript)
3Etiopatogenesis patological proteins
- neuritic plaques
- ? amyloid
- amyloid precursor protein (APP)
-
- ? sekretase
? sekretase - ? amyloid
? APP - plaques
transduction
4Etiopatogenesis 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
5Etiopatogenesisbrain atrophy
6EtiopatogenesisACh deficit
7Etiopatogenesis inflammation
Alzheimer - reactive astrocytes, microglia
activated microglial cells
8Etiopatogenesis genetic factors
9New criteria for AD diagnosis
- Impairment of episodic memory
- Atrophy of medial temporal structures on MRI
- Abnormal cerebrospinal fluid markers
- Specific metabolic pattern evidenced with
molecular neuroimaging methods - Familial genetic mutations
Dubois a kol., 2007
10Memory
- Epizodic memory significantly impaired
episodic memory - for recalling informations from
memory, it needs personal experience
11Clinical 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)
12Clinical criteria AD
- Deterioration of fatic, gnostic functions and
praxia - Apathy, agresivity, anxiety, depression
13B. 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
14Medial temporal structures on MRI
15Medial temporal structures on MRI
16MRI - hippocampus
17MRI - hippocampus
Alzheimer disease
Normal MRI
18C. Abnormal cerebrospinal fluid biomarkers
- Amyloid ?42 - A ?42 - ?
- Total tau protein t-tau - ?
- Phospho-tau protein p-tau - ?
19D. 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
2018F-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.
23E. Familial genetic mutations
- Tri autosomal dominant mutations cause AD
- Chromosome 21 amyloid precursor protein
- Chromosome 14 presinilin 1
- Chromsome 1 presenilin 2
24Diagnosis
- Laboratory tests
- Blood count, sugar, Na, K, urea, TSH, cholesterol
(total, LDL, HDL), B12, - others
25Therapy
- Increasing of cholinergic activity
- Acetylcholine inhibitors
- DONEPEZIL (ARICEPT)
- RIVASTIGMIN (EXELON)
- GALANTAMIN (REMINYL)
26Therapy
- Modulators of glutamatergic transmission
- Memantin blocer of NMDA receptor channels
27Therapy
- Behaviour problems
- Agressivity
- Insomnia
- Depression
28Lewy body dementia
- Memory loss
- Parkinson syndrome
- Visual halucinations
- Worsening after neuroleptics
29Frontotemporal 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
30Frontotemporal lobar degeneration - FTLD
- 3 types
- Frontotemporal dementia
- Primary progressive (non-fluent) aphasia
- Semantic dementia
31Frontotemporal 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
32Frontotemporal 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
33Frontal dementia
34Primary progressive aphasia
35Semantic dementia
36Vascular dementia
- Dementia
- - loss of cognitive functions
- - memory problems
- Cerebrovascular disease
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38Classification of VaD
- Multiinfarct dementia (K,S)
- Demencia after stroke in strategic localisation
- Small vessel disease (K,S)
- Hypoperfusion (surgery in older age ? risc
4-times) - Dementia after brain haemorrhage
- Other mechanisms
39Risk factors of dementia
- TIA
- Stroke
- Arterial hypertension
- Diabetes mellitus
- Atrial fibrillation
- Hyperlipidemia
40VaD vs AD
41Vascular dementia
- Sudden onset of cognitive decline, fluctuations
- ! Small vessel disease slow onset, slow
progression - Gait problems and falls
- Incontinentia in early stages
42Dg VaD - CT
43Dg. VaD - MRI
44Dg. VaD MRI
45Dg. VaD Ultrasound and AG
46Therapy VaD
- AChE Inhibitors and memantin ?
- Stroke prevention
- ASA, clopidogrel, dipyridamol ASA
- Anticoagulant th AF
- Therapy of risk factors