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Demantia,Alzheimer's diseases and related demantias.pptx
- 1. DEMENTIA/ ALZHEIMER DISEASE &RELATEDDISORDERS Dr. Hatice Ömercikoğlu Özden Nöroloji ABD
- 2. Dementia • Definition • Diagnosticcriteria • Epidemiology • Differential diagnosis typical features and treatment of certain dementia syndromes
- 3. Cognitive Domains • Executivefunction (frontal, hemispheric white matter) • Memory (medial temporal lobes/ hippocampus) • Language (left hemisphere, usually) • Visuospatial (occipital, parietal)
- 4. What is Dementia? •Impairment in intellectual function affecting more than one cognitive domains • Interferes with social or occupational function • Decline from a previous level • Not explained by delirium or major psychiatric disease 4 This Photo by Unknown Author is licensed under CC BY-SA
- 5. Cognitive Decline Depression Other psychDelirium Drug induced Dementias (“big four”) Alzheimer Vascular Lewy body / PD Frontotemporal Alcohol Recreational Prescriptions ! Many causes! Alone, or with dementia Trauma, tumor, MS, HIV, syphilis, NPH, subdurals, vasculitis, CJD Hepatic, renal, or thyroid disease Deficiency (B12) Toxins, OSA
- 6. Dementia is nota specific disease It’s a overall term that describes a wide range of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person’s ability to perform everyday activities
- 7. • Aphasia: isa language disorder that affects ability to comprehend or express spoken or written language or both. • The term apraxia is defined as inability to correctly perform learned skilled movements with the arms etc. • no weakness, • no ataxia, • no seizure, • no involuntary movement • Agnosia can be defined as inability to recognise familiar objects, faces, sounds or words.
- 9. Dementia: Epidemiology I •Over 65, about 5-10 % of population has some kind of cognitive decline. • This ratio reaches, 20-50 % of all population in the age of 85. • Dementia is a health problem both for the developed and developing countries.
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- 11. Classification of dementias •Primary degenerative dementias Dementia pure: neurodegenerative disorders primarily involving cerebral cortex • Alzheimer’s disease • Focal degenerations Dementia plus: neurodegenerative disorders involving additional brain areas such as basal ganglia or other subcortical structures • Dementia with Lewy bodies • Parkinson’s disease • FTD-Parkinsonism-17; FTD with motor neuron disease • MSA • Corticobasal degeneration • PSP • Huntington diseae • Some forms of SCA • Familial multiple system taupathy • Progressive subcortical gliosis
- 12. • Secondary formsof dementia • Disorders damaging the brain tissue directly • Vascular-ischaemic causes • Infections (HIV,Syphilis,Herpes simplex,Lyme disease) • Demyelinating disorders • Inborn metabolic disorders • Traumatic brain injury • Post-radiation dementia • Some brain tumors • Parasitic cysts or brain abscess • Disorders changing intracranial contents and distorting brain structures • Normal pressure or obstructive hydrocephalus • Subdural or intraparenchymal haematoma • Primary or metastatic brain tumors • Systemic diseases or conditions affecting the brain •
- 13. • Metabolic-nutritional : (Wernicke-Korsakoffdisease,Chronic alcoholism,B12 deficiency, Pellegra, Hepatic encephalopathy) • Endocrine: Thyroid disease, Parathyroid disease • Toxic: Organic solvent exposure, Heavy metal intoxication • Systemic immune-mediated or inflammatory disorders These are all treatable !
- 14. Alzheimer’s Disease Alzheimer’s Disease(AD) is a type of dementia that causes problems with memory, thinking, and behavior AD is the most common form of dementia AD worsens over time AD has no current cure
- 15. Alzheimer’s Disease: Genetics, prevalence,risk factors • In 5-10 % of AD patients disease shows an autosomal dominant trait. • It’s onset is at 30s or 40s. • APP (chromosome 21), presenilin1(chromosome 14) and presenilin2 (chromosome 1) mutations cause this type of inheritance. • All of them result in excessive production of insoluble ß amyloid . • In patients with Down syndrome the AD pathology occurs when they are 30-40 years old because of the over-production of ß amyloid due to the existence of an extra chromosome 21.
- 16. Alzheimer’s Disease: Genetics, prevalence,risk factors II • In 90-95 % of the patients AD does not show an autosomal dominant transmission. • The disease onset is at about their 65s. • But in this group, some of the patients come from the families where the prevalence of AD is higher than general populations (nondominant familial AD). • The rest of the patients comes from families, their prevalence of AD is similar to that of the general population (sporadic AD).
- 17. Alzheimer’s Disease: Genetics, prevalence,risk factors III • The most important risk factor for AD is age. Prevalence doubles for every 5 years after the age of 65 (10%) and reaches 40% among those older than 85. • Head injury, female gender and a positive family history are other known risk factors. • An additional risk factor has been linked to chromosome 19 that encodes apolipoprotein E (ApoE). • The e4 allele frequency is 20% in the general population and 40% in AD.
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- 22. AD: Clinical Picture •AD is an amnestic dementia with an insidious onset and indolent course. • It causes disturbances in daily living activities, behavioural symptoms and cognitive decline. • Diagnosis death about 15-20 years. • Symptoms change as the pathology of the disease progresses.
- 23. AD: Initial StageI • Memory problems • forgets names, repeat themselves, misplaces their belongings, makes lists • may fluctuate in intensity, good for remote events and recent events with high emotional impact. • poor for ordinary recent events • clues and multiple choices are useful.
- 24. AD: Initial StageII • Language and behavioural problems • speech becomes less fluent and loses spontaneity. • difficulty in word finding. • Self awareness of impairment may elicit depression. • may keep working, especially when he/she is protected by understanding staff in his/her office. • may have some difficulties in choosing dress, complex financial tasks. • may keep house, pay bill, drive car, participate social activities
- 25. AD: Intermediate StageI • Memory problems • recognition difficulties (forgets remote events) • forgets faces • inability to use clues or lists • spatial orientation disturbances (getting lost in unfamiliar environment) • inability to store new data (even for minutes)
- 26. AD: Intermediate StageII • Language and behavioural problems • word finding difficulty in ordinary conversations • increased misunderstanding • become indifferent to their symptoms, depression subsides. • paranoid ideation (spousal infidelity, stolen personal object due to misplacement) • sun downing (worsening of cognitive and behavioural symptoms at the end of the day) • Independency in housekeeping, dressing, bathing, grooming, paying bills are gradually lost
- 27. AD: Final StageI • Memory problems • living in past • inability to recognize family members • family members recognized as if they are not themselves (they recognized as their imitations) • getting lost even in familiar surroundings • inability recognize home and rooms
- 28. AD: Final StageII • Language and behavioural problems • incoherent speech • loss of speech • wandering • purposeless movements • crying • agitation • difficulties in moving and feeding, bathing, continence towards the end of stage • myoclonus, rigidity, gait difficulties • become bedridden and death due to infections or emboli.
- 30. Laboratory Tests Routine • Bloodglucose • CBC • Chest X-ray • Vitamin B12 level • Thyroid function tests • AST, ALT • LDH • BUN • Uric acid • Sedimentation rate • Syphilis serology • CT, MRI Optional • ECG • EEG • Drug levels • Urinalysis • HIV testing • Heavy metals in urine • CSF analysis • PET/SPECT • CSF AMYLOID and TAU/PHOSPHOTAU
- 31. Treatment-I • Cognitive symptoms •Centrally active cholinesterase inhibitors • Donepezil (Aricept 5 mg) 1x1 at bedtime for 1 month then 1x2 • Rivastigmin ( Exelon 1,5; 3; 4,5 and 6 mg) 2x1 increase dose one step for one week, max 2x6 mg • NMDA-receptor antagonism • Memantin 20mg/day
- 32. Treatment – IIBehavioural symptoms Psychotic features Typical neuroleptics (avoid in Lewy body dementia) Haloperidol Thioridazine Chlorpromazine Sulpiride Pimoside Atypical neuroleptics Clozapine(!) agranulocytosis Olanzapine Risperidone Quetiapine Depressive features (Avoid antidepressants with prominent anticholinergic effect) SSRI’s Fluoxetine Sertraline Citalopram SNRI’s Venlafaxine
- 33. Treatment – III Sleepdisturbances Trazodone Anxiety benzodiazepines beta blockers Mood Stabilisers Valproate Na Gabapentine Carbamazepine Lithium
- 34. Treatment – IV •Antioxidants • Gingko biloba extracts • Vitamin E • Vitamin C • Estrogens (as antioxidant and acetyl choline production enhancer) • Anti inflammatory drugs • COX-2 inhibitors • Indomethasine
- 35. Treatment - V •New Drugs for Alzheimer’s Disease • Disease- modifying therapy (DMT) is the central concept in the development of AD therapeutics today • DMT drugs that are currently in clinical trials are anti-Aβ drugs, such as aducanumab and lecanemab. • Aducanumab, which received FDA approval in June 2021 is anti-Aβ antibody targeting Aβ aggregates and is the first approved antibody therapy for AD.
- 36. Non-Alzheimer Dementias: Frontotemporal Dementia • Early deteriorationin social conduct, personality, initiative, insight and attention • Rudeness, disinhibition and distractibility • Speech--->Non fluent and reduced in quantity • Visio-spatial abilities, EEG and memory are normal (at least in the beginning). • Familial forms are linked to the chromosome 17 • May occurs with parkinsonian symptoms and ALS in the same patient
- 37. Non- Alzheimer Dementias: Lewy Body Dementia • Cortexand subcortical areas(basal ganglia and locus coeruleus) contain Lewy bodies that is made of alfa synuclein as in Parkinson’s disease. • Mild parkinsonian symptoms begin with dementia is the hallmark. • Symptoms may fluctuate during the day • Visual hallucinations and increased susceptibility to the typical neuroleptics are the other key features
- 38. Non- Alzheimer Dementias: Vascular Dementia • National Instituteof Neurological Disorders and Stroke (NINDS) criteria: • Cerebrovascular disease (CVD) as defined by the presence of focal signs on neurologic examination such as: hemiparesis, facial weakness, Babinski sign, sensory deficit, hemianopia, dysarthria consistent with stroke (with or without history of stroke). • Evidence of relevant CVD by brain imaging including multiple large-vessel infarcts or a single strategically placed infarct (angular gyrus, thalamus, basal forebrain), as well as multiple basal ganglia and white matter lacunes or extensive periventricular white matter lesions, or combinations thereof. Other criteria include. • Any combination of onset of dementia within 3 months following a recognised stroke. • Abrupt deterioration in cognitive functions. • Fluctuating or stepwise progression of cognitive deficits. • Hypertension.
- 39. Ways to Possibly Reduce Chances of Developing Dementia CognitivelyActive Socially Active Physically Active Healthy Diet
Editor's Notes
- #21 The disease process begins from entorhinal cortex and in the earliest detectable stage of dementia at least 50% of neuronal loss can be found in the layer II neurons. The neuronal loss then become detectable in the superior temporal sulcus as the disease and the cognitive decline increases. As the neuronal loss continues, the two core pathological features of AD; neurofibrillary tangles (NFT) and neuritic plaques become more prominent in the pathological specimens. The occurrence and density of NFT seems more related to the progression of symptoms and the disease process in the brain than plaques.
- #38 Lewy body dementia: In 15-20% percent of the patients with the diagnosis of AD, subcortical areas such as basal ganglia and locus coeruleus contain Lewy bodies as is typical in Parkinson’s disease. But the patients also have this pathology in their cortical areas. Lewy body dementia has been considered as between AD and idiopathic Parkinson’s disease clinically. Patients show mild bradykinesia, masked face, flexed posture and gait difficulty without resting tremor. Dementia is not as severe as in AD. Symptoms may fluctuate during the day and increased susceptibility to the neuroleptics considering extrapyramidal side effects are the key features.