Dementia syndrome

Definitions The disturbance and symptoms significantly interfere with work or usual social activities or relationships with others The syndrome associated with a progressive loss of memory and other intellectual functions that is serious enough to interfere with performing the tasks of daily life The decline in intellectual function, including difficulties with language, simple calculations, planning and judgment, and motor (muscular movement) skills as well as loss of memory

Signs and symptoms loss of cognitive ability memory attention language problem solving disorientation in time, in place, in persons behavioural problems emotional changes depression, anxiety, paranoia

Causes neurodegenerative diseases Alzheimer´s disease Parkinson´s disease stroke trauma chronic alcohol abuse Korsakoff´s syndrome genetic diseases Huntington disease metabolic diseases Tay-Sachs disease Gaucher disease infections Creutzfedt-Jakob disease viral encephalitis

The most frequent: Alzheimer´s disease 50-60% Vascular dementia Dementia with Lewy bodies Frontotemporal dementia 80% 90%

Alzheimer´s disease

History 1901 - German psychiatrist Alois Alzheimer identified the first case of what became known as Alzheimer's disease in a 50-year-old woman he called Auguste D (A. Deter). Alzheimer followed her until she died in 1906, when he first reported the case publicly. Alois Alzheimer Auguste D

Characteristics 4 stages Pre-dementia mild cognitive difficulties memory loss - remembering recently learned facts and inability to acquire new information subtle problems with attentiveness, planning, flexibility, abstract thinking Early dementia the increasing impairment of learning and memory difficulties with language - shrinking vocabulary and decreased word fluency executive functions, perception (agnosia), or execution of movements (apraxia)

Moderate dementia inability to perform most common activities of daily living speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions reading and writing skills are also progressively lost complex motor sequences become less coordinated - risk of falling increases memory problems worsen – problems to recognise close relatives behavioural changes – irritability, lability, aggression urinary incontinence Advanced dementia completely dependent upon caregivers language is reduced to simple phrases or even single words, or complete loss of speech extreme apathy and exhaustion not be able to perform even the most simple tasks without assistance immobility, they lose the ability to feed themselves death (infection, pneumonia)

Risk factors Higher risk od AD age 65 – 75 y 3% 75 – 85 y 19% Lower risk of AD ?? antioxidants (ginkgo biloba) ? estrogens ?? ibuprofen ?? smoking ????? Higher risk od AD age 65 – 75 y 3% 75 – 85 y 19% > 85 y  50% positive family history low degree of education depression women > men trauma of head

Macroscopic changes brain atrophy – temporal lobe, parietal lobe, frontal cortex, cingulate gyrus enlargement of ventricles

Microscopic changes loss of neurons and synapses in the cerebral cortex amyloid plaques neurofibrillary tangles

Amyloid plaques (senile plaques) dense, mostly insoluble deposits of beta-amyloid peptide outside and around neurons beta-amyloid - small peptide (39–43 amino acids)  a fragment from the amyloid precursor protein (APP) – a transmembrane protein of neurons APP is critical to neuron growth, survival and post-injury repair in Alzheimer's disease, an unknown process (mutation of APP gene?) causes APP to be divided into smaller fragments by enzymes (proteolysis) accumulation of aggregated amyloid fibrils – toxic - disrupting the cell's calcium ion homeostasis, induces apoptosis (hypothesis)

Neurofibrillary tangles aggregates of fibres hyperfosforylated protein tau - accumulate inside the cells normal function of tau protein - stabilizes the microtubules (important for transport in neurons) – microtubule-associated protein in AD - tau is hyperphosphorylated – composes pairs with other threads, creating neurofibrillary tangles and disintegrate the neuron's transport system

Other factors Presenilins 1 and 2 – transmembrane proteins mutations in Alzheimer disease Allele e4 of apolipoprotein E 3 alleles – e2, e3, ee4 e4 – higher risk of atherosclerosis and Alheimer disease

The mini-mental state examination (MMSE) or Folstein test - brief 30-point questionnaire test - used to screen for cognitive impairment. Category Possible points Description Orientation to time 5 From broadest to most narrow. Orientation to time has been correlated with future decline. Orientation to place From broadest to most narrow. This is sometimes narrowed down to streets,[and sometimes to floor.[ Registration 3 Repeating named prompts Attention and calculation Serial sevens, or spelling "world" backwards. It has been suggested that serial sevens may be more appropriate in a population where English is not the first language. Recall Registration recall Language 2 Name a pencil and a watch Repetition 1 Speaking back a phrase Complex commands 6 Varies. Can involve drawing figure shown.