Dementia

Increased age Cardiovascular disease Infections Lifestyle factors - smoking, obesity Neaurological diseases Trauma head injuries Environmental toxins Hormonal

Age, sex, gender Ethnicity Genetics cognitive impairment in childhood

Obesity Cardiovascular disease Smoking and alcohol use Traumatic brain injury (TBI) Infection

Brain disorder that effects the thinking, behaviour and ability of a person to preform tasks and brain functions

Alzheimer’s disease (40-70%)

These proteins are found within the brain and they stabilise microtubules, abundant in the neurons of the nervous system and are less common everywhere else

If they become impaired and become injured then they trigger/exacerbate changes in Tau and amyloid-beta (AB) pathologies

The formation of amyloid and neurofibrillary tangles (NFTs) as well as neuronal dysfunction

Medicated by activated microglial cells which are a source of Cytokines

Neuroinflammation activated cytokines Disturbances in cerebral glucose metabolism also effects AD Increase in circulating Interleukins and tumour necrosis factor-alpha (A) buildup C-reactive protein and interleukins-6 can predict congnative decline Microglia circulate the brain looking for infection or inflammation caused by toxic proteins that might damage neurons The result: more and more damaged neurons which can lead to the onset of AD

They are key compound in the brains inflammatory response. They are triggered by pro-inflammatory and anti inflammatory events, stimulated by injury, ischaemia and beta-amyloid toxicity. Cytokines (interleukin 1) and tumour necrosis cause ongoing inflammatory responses, such as the amyloid cascade. Inflammatory process also increases the presence of vascular injury, hypertension, atherosclerosis and high blood cholesterol. Presence of Chromic inflammatory cells (Neutrophils, T cells CD4 and CD8 positive T cells and Macrophages) all within the walls of the blood vessels in the brain

Amyloid beta proteins (APP) are proteins found in the cell membrane at the synapse of the neuron - regulate synapse formation In AD the abnormal process of APP results in the formation of beta-amyloid which is toxic, they come from larger proteins found in the fatty membrane o surrounding nerve cells. Beta-amyloid is “sticky” and clumps together to form plaques, the abnormal clusters of proteins buildup between nerve cels and block the cel to cell signalling at synapses. They also activate the immune system cells (microbial) trigger inflammation and destroy the synapse.

Subcortical - Acetylcholine, noradrenaline, serotonin Cortical - somatostatin, glutamate

Plays a crucial role in information processing and memory

Loss of cholinergic neurons in the basal forebrain, decreased acetylcholine levels and a decrease in the acetylcholine synthesising enzyme choline acetyltransferse (CHAT) in the cerebral cortex

Further reduction in neurotransmitters. Neurodegeneration leads to neurotransmitters depletion, which leads to further neurodegeneration

Mode of action - improve cognitive functions by inhibiting acetylcholineesterase from breaking own the neurotransmitter acetylcholine into chlorine and acetate Increasing levels and duration of action of acetylcholine in central nervous system. Shown to improve cognitive functions Side effects - Vomiting Muscle cramps diarrhoea

Donepezil Glantamine Rivastigmine

Mode of action - improve cognitive function by reducing the amount of of glutamate. Prevents entry of calcium ions into the neurons, excess calcium damages neurons and prevents receiving messages from other neurons In AD lots of glutamate leaks out of damaged cells interfering with learning and memory Side effects - Headache Dizziness Heartache Allergies

Memantine

When behavioural and psychological symptoms are severe and resist other treatments - side effects can be significant

Mode of action - they increase monoamine neurotransmitters in the brain, serotonin, dopamine, norepinephrine and histamine Side effects - Drowsiness Stiff muscles Increased risk of stroke, TIA and death

Low vitamin B 12 Omega 3 supplements Balanced diet

• Memory changes • Withdrawal from usual activities • Disorientation to time and place • Visual-spatial difficulties • Decrease in written or verbal communication • Challenges in problem solving and planning • Personality and mood changes • Misplacing items frequently • Decline in judgement • Difficulty preforming familiar tasks