Alzheimer's Flashcards
what is the definition of AD?
Alzheimer’s disease (AD) is a chronic neurodegenerative disease with an insidious onset and progressive but slow decline. AD is the most common type of dementia.
what is the epidemiology of AD?
Most common dementia Prevelce 5% in europe More common in women More common in vlakc and hispanic people than white people Early onset is often inherited (<60yrs)
what is the aetiology of AD?
The brains of people with AD have an excess of interneuronal amyloid (Abeta) peptides, due to overproduction or diminished clearance of beta-amyloid. This leads to the formation of dense amyloid oligomers, which are deposited as diffuse plaques. These oligomers and plaques cause an inflammatory process through microglial activation, cytokine formation, and activation of the complement cascade. Inflammation leads to the formation of neuritic plaques, causing synaptic and neuritic injury and cell death. However, interventions aimed at preventing Abeta accumulation have failed to demonstrate clinical efficacy in preventing or slowing AD progression
Lifestyle factors such as smoking, midlife obesity, a diet high in saturated fats, abstinence from alcohol in midlife, and consumption of >14 units of alcohol/per week have been associated with an increased risk for the development of AD.
Genes mutated - APP, PSEN1, PEN2
what are the risk factors for AD?
Advance age Family history Genetics Down’s syndrome CV disease (+all other risk factors for this e.g. smoking and obesity) Lifestyle actors and medications Less than secondary school education
what is the pathophysiology of AD?
Gross examination of the brains from people with AD reveals reduced brain weight: typically 100-200 g less than average, or more depending on disease severity. Cortical atrophy is apparent in the temporal, frontal, and parietal areas, whereas the thalamus, brainstem, cerebellar hemispheres, and basal ganglia usually appear normal in size and weight.
On microscopic examination, senile plaques and neurofibrillary tangles are the characteristic histopathological features postmortem. Plaques are made up of beta-amyloid and are extracellular, whereas neurofibrillary tangles are intracellular and composed of cytoskeletal filaments of hyperphosphorylated tau. These changes are usually present in the hippocampus, amygdala, cortex, and nucleus basalis. The abundance of tangles is roughly proportional to the severity of clinical disease and cognitive decline.
Possible mechanisms by which beta-amyloid induces injury to brain cells include intracellular calcium deposition, production of oxygen radicals and nitric oxide, and inflammatory processes.
Cholinergic neurons are damaged in the basal forebrain, which results in decreased levels of cholinergic neurotransmission. Other findings include degeneration of the locus caeruleus and raphi nuclei, with subsequent neurotransmitter deficiencies in serotonin, corticotropin-releasing factor, glutamate, and noradrenaline (norepinephrine).
what are the key presentations of AD?
Risk factors Memory loss Disorientation Nominal dysphasia Misplacing items Getting loss Apathy IADLs personality change Unremarkable initial physical examination
what are the first line and gold standard investigations for AD?
Bedside cognitive testing - impaired recall, nominal dysphasia, disorientation (to time, place, and eventually person), constructional dyspraxia, and impaired executive functioning
FBC - rule out anaemia
Metabolic panel - exclude abnormal sodium calcium and glucose levels
Serum TSH - rule out thyroid related dementia
Serum vit B12 - rule out deficiency induced dementia
Urine drug screen - rule out recreational drug use
CT - exclude space occupying lesions
MRI - generalised atrophy with medial temporal lobe and later parietal predominance
Could do - CSF testing (amyloid and tau markers)
what are the differential diagnoses for AD?
Delirium
Depression
Vascular dimension
Lewy body dementia
how is AD managed?
Supportive care, at home safety assessment, assessment of driving, cholinesterase inhibitor (donepezil: mild to moderate disease: 5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day; moderate to severe disease: 5 mg orally once daily initially, increase gradually according to response, maximum 23 mg/day), management of symptoms (depression, psychosis, insomnia etc.)
how is AD monitored?
Patients should be seen at least every 6 months to evaluate for functional and cognitive change. Issues such as daily medication use, functional status, comorbid illnesses, new signs and symptoms, carer burden, and need for future respite care or nursing home placement should be discussed. Medication continuation may be discussed if the disease progresses without apparent symptomatic benefit or plateau. Home safety risk assessment should be made at every visit.
what are the complications of AD?
Pneumonia
Institutionalisation
UTI
Falls
what is the prognosis of AD?
Many admitted to nursing homes for daily care in advanced disease
Severe clinical features later on - hallucination, seizures, infections, weight loss, strokes etc. - this is usually what causes death
