ALZHEIMER S DISEASE Definition Activities of daily living eating bathing dressing toileting taking medications Instrumental activities of daily living activities performed by someone living independently in the community such as shopping managing money cooking managing medications Mental capacity to control and purposefully apply one s own mental skills Mini Mental State Examination MMSE is used to help diagnose dementia and assess its progression and severity Non cognitive symptoms related to dementia such as irritability anxiety depression agitation delusions or hallucinations Accumulation of beta amyloid around synapses that interferes with neuronal transmission and contributes to cell death Dissociation and aggregation of hyperphosphorylated tau protein within the neuron causing collapse of the microtubules o APOE 4 chr 19 o o o Amyloid precursor protein chr 21 Presenilin 1 chr 14 Presenilin 2 chr 1 Possible Risks CVD risk factors o Heavy smoking o HLD o HTN o DM o Obesity Head injury o o Trauma Traumatic brain injury APP cleaved by alpha secretase red and then gamma secretase aqua In Alzheimer s disease APP is cleaved by beta secretase orange at a different site The longer fragment is called beta amyloid Beta amyloid fragments form oligomeres congretate to form plaques in neuronal tissue oxidative and inflammatory injury ultimately synaptic failure Medical Terminology Term ADL IADL Executive function MMSE Behavioral symptoms of dementia Amyloid plaques Tangles Epidemiology 2 3 are women Etiology Risk factors Age Genetics Down Syndrome Pathophys Amyloid Cascade Occurs outside neurons Formation of beta amyloid plaques interferes w neuronal transmission cell death Amyloid precursor protein Presenilin 1 Presenilin 2 Neurofilbrillary Tangles Hyperphosphorylated tau protein block transport of nutrients Microtubule collapse Occurs within neurons Microtubules are composed of tubulin and stabilized by tau proteins In AD tau becomes hyperphosphorylated and insoluble therefore dissociating from tubulin Tau proteins forms paired helical molecules which may be cytotoxic Tau proteins form insoluble filaments and tangles in axons Accumulation of tangles denotes severity of disease Loss of microtubules leads to synaptic failure cell injury and eventually neuronal death Inflammatory response to clear amyloid protein Release of cytokines nitric oxide other free radicals Inflammatory Immunologic Hypothesis Ventricles grow larger Hippocampus shrinks o Memory formation Brain Cortex shrivels up Thinking Planning o o o Remembering Diagnosis NCD Neurocognitive Disorder Mild Modest decline in one or more cognitive domains Does NOT interfere with independent living Cognitive Domains Major NCD Etiology Complex attention Executive function Learning and memory Language Perceptual Social cognition Alzheimer s Interferes with independent living Insidious onset and gradual progression Decline in one or more cognitive domains Classify as probable or possible Major NCD due to Alzheimer s disease Probable Alzheimer s disease Major Significant decline in one or more cognitive domains Substantial impairment that interferes with independent living Specify Mild moderate severe With without behavioral disturbance Alzheimer s disease Frontotemporal Lewy body disease Parkinson s disease Vascular disease Traumatic brain injury Substance medication use HIV infection Prion disease Genetic mutation obtained from family history or genetic testing All 3 of the following o Decline in memory and learning and at least one o other cognitive domain Steadily progressive gradual decline in cognition without extended plateaus o No evidence of mixed etiology NCD Etiology from most common to least Alzheimer s Memory Language Visual spatial disturbances Delusions Vascular Abrupt onset Stepwise deterioration Executive dysfunction Gait changes Lewy Body Visual hallucinations Delusions Fluctuating mental status EPS Frontotemporal Personality changes Executive dysfunction Excessive eating drinking Indications Onset 60 Lab Tests Routine TSH r o hypothyroidism B12 r o anemia Folate Serum calcium Liver kidney fx to select tx Electrolytes Diuretics SSRI SNRI decrease level of Na Targeted Biomarkers research HIV if risk factors present MoCA Montreal Cognitive Assessment BIMS Brief Interview for Mental Status Cognition Screening Cognition Staging MMSE Agitation Testing Imaging Type CT Structural MRI more common allows to rule out differentials stroke brain damage fractures Functional amyloid PET scan n a 21 26 11 20 10 Mini Cog MCI Mild Moderate Severe Behavioral Symptoms Lifetime risk 100 Assessment Identify target symptoms Quantify adverse behaviors Severity Frequency Symptoms Psychosis Anxiety Depression Progression of Disease Agitation Apathy Aggression Subtract other causes when possible Drugs Acute medical conditions Environmental factors Treatment A Caregive Support B Non pharm 1st line for behavioral symptoms Cognitive interventions Environmental modifications Changes in activity demand Reorientation reminders cues Adjustment of noise level reduction of clutter figure 8 walkways masking doors Reduction in the amount and complexity of activities Interpersonal approaches Simplified language focus on patient s wishes and concerns C Pharm Tx Algorithm Tx Controversies Switching between ChEIs doesn t improve efficacy but might improve SE s o If no efficacy after 3 6 months or tolerability issues o Hard to determine failed efficacy Monotherapy vs dual therapy When to stop therapy 1 Cholinesterase inhibitors ChEIs MOA Ach released into synapse In Dementia there s decreased Ach drug binds to Ach and allows for more to reach the synapse Donepezil mild severe Initial 5mg qHS 2 5mg if GI SE s intolerable Increase to target 10mg qHS 4 6 weeks o o o High dose 23mg o No dose adjustments Galantamine Rivastigmine patch mild moderate can be used for severe there s just not clinical trials done for this population off label use Tacrine liver issues DONOT use N V D take w food or at night Insomnia nightmares agitation panic anxiety Muscle cramps weakness Bradycardia tremor dizziness Dementia patients are more likely to use anticholinergics Older adults are more sensitive to CNS effects Consider cumulative anticholinergic burden A w delirium and cognitive impairment Adverse effects o GI o CNS o Neuromuscular o DI s CV o Anti ACh o Digoxin BB s CCB s Bradycardia Dosing Tips o If side effects develop during initiation Slow rate of dose escalation Advance