1. M. Alzheimer

3. Etiopatogenesis patological proteins u neuritic plaques u  amyloid u amyloid precursor protein (APP)  sekretase  sekretase  amyloid  APP plaques transduction

4. Etiopatogenesis patological proteins  Neurofibrillar tangles u tau protein u in CNS – stabilization of microtubullar network u 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. Etiopatogenesis brain atrophy

6. Etiopatogenesis ACh deficit

7. Etiopatogenesis inflammation activated microglial cells Alzheimer - reactive astrocytes, microglia

8. Etiopatogenesis genetic factors

9. New criteria for AD diagnosis A.Impairment of episodic memory B.Atrophy of medial temporal structures on MRI C.Abnormal cerebrospinal fluid markers D.Specific metabolic pattern evidenced with molecular neuroimaging methods E.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

16. MRI - hippocampus

17. Alzheimer diseaseNormal 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

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