Alzheimer's Disease and Dementia with Lewy Bodies PDF

Alzheimer’s disease and dementia with Lewy bodies I- Alzheimer's disease The current context : Alzheimer’s disease does not begin at the stage of dementia Around 5 to 8 years before the patient might have a cognitive impairment but if we do cognitive tests we do not find anything. Before d...

Alzheimer’s disease and dementia with Lewy bodies I- Alzheimer's disease The current context : Alzheimer’s disease does not begin at the stage of dementia Around 5 to 8 years before the patient might have a cognitive impairment but if we do cognitive tests we do not find anything. Before dementia, you have 20 to 30 years of lesions with few symptoms. Dementia is when a person is not able to do something because of cognitive dysfunction. The duration of dementia is 10 to 30 years (because of the lesion) Amyloid plaques (Abeta peptide) and tangles (Tau) Tau accumulation is responsible for tangles. We have inflammation aspects with microglial activation. Because the inflammation in the blood will got to the brain and cause lesions to lead to cognitive impairments. When we have peripheral inflammation we have an aggravation of AD. Extension of tangles in AD : Tangles : it begins in trans entorhinal region. It is correlated with negative aspects : attentional, memory, executive dysfunction. Usually, patients don’t have any visual impairments. The motor cortex is not impacted. Pathophysiology : Accumulation of Tau → tangles Plaques of A-beta → activation of microglia Astrocytes Epidemiology : In France, 1 million people with AD, among 1.3 million people with dementia 110 000 new cases every year Prevalence according to PAQUID : - 4% between 75 and 80 years old - 20% between 80 and 90 years old - 40% after 90 years old The most important risk factor in AD is aging. Estimated prevalence of dementia in France from 2010 to 2030/Prevalence after 90 years Risk factors : - Age - Familial history of AD (risk ratio x3 if 1st degree parent reached) - Genetic risk factor : ApoE4 (risk ratio x2 to 16 depending of the number of allele) - Female sex (risk ratio x 1.5 to 2) - Low level of education (protection thanks to « cognitive reserve ») - Brain injury - Pesticides (risk ratio x 1.38), particularly organophosphorus (risk ratio x 1.53) - All the vascular risk factors , particularly High Blood Pressure - Atmospheric pollution A study : How can we lower the chance of AD ? If we care about all the factors → we can diminish the risks of AD to 40% Consequences for caregivers : At the stage of MCI (barely AD) takes 2 hours to help the patient. At the stage of Severe dementia, it’s 9 hours each day. ➔ Early diagnosis and adapted care for each stage Early diagnosis : the clinical evaluation First, the clinical evaluation is essential with - History of the patient (depression, vascular risk factors, syndrome of sleep apnea) - History of the cognitive complaint. - Current treatment - Physical examination (Parkinsonism ?) - Neuropsychological tests : duration about 2 hours Because , only 25% of Alzheimer’s disease patients in memory clinics in Alsace and France… so many other diseases with cognitive impairment, and other treatment One syndrome, many Diseases For each symptom, there can be several diseases possibles. Neuropsychological test : During 1 to 2 hours The aim : to test the main cognitive functions - Memory (long term memory) - Language - Praxis : coordination of the body - Executive functions - Speed processing : quick, normal ? - Attention Evolution : Pre clinical phase : slow and progressive constitution of the lesions, without clinical sign (or subjective complaint = SCI) Pre dementia phase = Mild Cognitive Impairment = MCI (or mild neurocognitive impairment) : duration 2 to 5 years - Memory impairment (Hippocampus) → no tangles or plaques (in early stages ?) - Emotional modifications (Amygdala) - Patient autonomous (IADL) IADL : Instrumental activities of daily living : What he can or can’t do Alzheimer’s disease : various forms of onset : - Hippocampal form (80%): memory storage disorder  - Aphasic (language impairments) form 10% (under 65 years): ” logopenic aphasia” → logopenic = have decrease speed of language - Posterior form or posterior cortical atrophy: 10% (under 65 years), also occipital lesion = simultagnosia = no more knowledge of what are objects when they are together, impossible to make difference between them - Frontal form: rare, with behavioral disorders Evolution : During dementia - Memory and emotional disorders worsen. - Other cognitive disorders appear (language disorders, praxies…) - Behavioral disorders - Impact on the autonomy and the relational life of the patient Death 8 to 20 years after diagnosis of dementia - By intercurrent pathologies (Cancer, cardio vascular…) - By complications of grabatization Evolution : MMSE decreases form 1 to 1.5 points out of 30 per year A lot of AD + DLB (dementia) → decrease in only 4 years. Behavioral symptoms in AD AD is also a behavioral disease, not only cognitive → comes from frontal and temporal lobes. Depression → correlation to atrophy in the right frontal lobe. Early diagnosis : biomarkers Brain MRI: atrophy of hippocampal and parietal regions ECD or HMPAO SPECT, or FluoroDesoxyGlucose PET: temporal and parietal hypometabolism CSF: p Tau, Tau, Abeta42 (decrease of Abeta 42 because of plaques), Abeta40 Research for PET: Florbetaben, Florbetapir, PIB Hippocampal atrophy : 1st : lot of CSF, 2nd : decease of CSF Parietal atrophy : We can do FDG PET : fluoro desoxy glucose : CSF : Norms ng/L : Abeta42>500 Tau = 100 à 300-500 Phospho-Tau