What is Medicine – Alzheimer Disease
ESSENTIAL DESCRIPTION Alzheimer disease (AD) is a degenerative, progressive, and irreversible neurologic condition that kills neurons. AD accounts for 60–80% of dementia. In the US, AD is the sixth most common cause of death. Alzheimer's disease (AD) is underdiagnosed (50%) and >50% of those with AD are ignorant of their diagnosis. The economic cost in 2018 was $305 billion, and by 2050, it is expected to reach $1.1 trillion. Dementia should be separated from: - Age-related cognitive decline: permanent modifications to mental capacity and memory; a result of natural ageing Greater impairment than cognitive decline is mild cognitive impairment (MCI). MCI: From a cognitive standpoint, most people are able to live independently. MCI: affects 15–20% of people under 65, and 32–38% of those people will develop dementia within 5 years. AD diagnostic classification: Preclinical AD has no cognitive symptoms, but has AD biomarkers. MCI from AD typically has memory issues. - AD-related dementia Early stage: memory impairment >MCI; Middle stage: communication and environment response impairment; Late stage: loss of ability to recognise and respond to environment properly; Affected System(s): Nervous Synonym(s): Alzheimer-type senile dementia; presenile dementia EPIDEMIOLOGY Females outnumber males in incidence and prevalence and are more prevalent in people over the age of 65. Incidence 484,000 new cases of AD are reported annually in the US . 2 new instances for every 1,000 adults aged 65 to 75. From the ages of 75 to 84: 11 new cases per 1,000 individuals 85 years: 37 new instances for every 1,000 individuals There are 5.8 million cases in the US; 44 million cases worldwide; 13.8 million cases in the US by 2050; and 1 in 10 of people 65 years and older have AD dementia. 32% of people over 85 have AD dementia. There are 200,000 Americans under 65 who have early-onset AD. AETIOLOGY AND PATHOPHYSIOLOGY Age, genetics, systemic diseases, and lifestyle choices may all affect the progression of AD. -Amyloid plaques outside of neurons and protein tangles inside of neurons, resulting in loss of connections and neuron death. Genetics: Autosomal dominant: 5% of AD, typically appearing before age 65. Nonautosomal dominant AD (familial inheritance): 15–25% of AD Non-modifiable risk variables include age, gender (owing to women's longer lifespans), family history, and genetic mutations. - APOE-e4 gene variant: e4 homozygous risk is 8 times higher than e4 heterozygous risk. – There are racial and ethnic variations in AD. Risk factors for cardiovascular disease include: - Hyperlipidemia and hypertension (HTN), particularly in midlife - Diabetes, obesity, and a decreased ability to metabolise glucose - Smoking, a poor diet, and a lack of exercise - Stroke risks and harm from cerebrovascular disease Additional risk elements that may be altered include: - Fewer years of formal schooling (8th grade) - Insufficient ongoing learning - Mild, moderate, and severe recurrent traumatic brain injuries - Social isolation - Late-life depression - Insufficient and poor-quality sleep - Deficits in hearing and vision - Heavy alcohol use - Potential environmental variables (such as pollution). DURATIONAL PREVENTION People under the age of 50 are most concerned about cognitive decline and impairment. HTN control, more exercise, and cognitive training may slow or stop cognitive ageing, MCI, and AD. NSAIDs, oestrogen, and vitamin E do not postpone the beginning of AD; statins and proton pump inhibitors have inadequate data to support their use. Healthy habits could stop or delay the onset of AD. Manage psychiatric disorders and prevent delirium while patients are in the hospital. COMMONLY ASSOCIATED CONDITIONS Depression Down syndrome The "Welcome to Medicare" preventive visit and the Medicare Annual Wellness Visit both call for a cognitive function assessment. Excluding delirium is necessary for the diagnosis of dementia. A comprehensive H&P, cognitive exam, and other diagnostic procedures are required to identify a specific dementia type. - DSM-IV-TR criteria from 2000: The ability to operate at work, at home, or in social situations is significantly hampered by a progressive deterioration in at least two areas of memory, executive function, attention, language, or visuospatial abilities. - As of 2013, the DSM-5 refers to "neurocognitive disorder" rather than "dementia," and lists the following cognitive impairments as neurocognitive disorders: complex attention, executive function, learning and memory, language, perceptual motor, and social cognition. Include an informant from your history, such as a family member, friend, or carer. - Memory loss that interferes with daily activities - Difficulty finishing routine tasks - Challenges in planning and problem solving - New word problems in speaking or writing - Difficulty with spatial relationships or visual images - Changes in mood or personality - Loss of the ability to remember where things are or how to get there - Reduced or poor judgement - Withdrawal from social or professional activity - Time and location confusion. Exam should rule out other dementia or delirium causes. Noncognitive parts of physical exam frequently normal for age, with the exception of late stage AD. ● Neuro: speech, language, vision, hearing, gait, balance, reflexes, muscle strength and tone, tremor, abnormal movements (akathisia, bradykinesia/dyskinesia) ● Late stage: skin lesions, nutrition-hydration status ● Brief cognitive testing, such as: Mini-Cog, Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE, under copyright, fee for use) ● Assess depression: Patient Health Questionnaire-9, Geriatric Depression Scale (GDS). Functional evaluation methods include the Functional Activities Questionnaire (FAQ) and instrumental activities of daily living (IADLs). DIFFERENTIAL DIAGNOSIS Additional dementias (most prevalent): - Vascular; mixed type (with AD); big and microvessels - Parkinson's disease; normal pressure hydrocephalus; dementia with Lewy bodies; frontotemporal lobar degeneration - Wernicke-Korsakoff, Huntington, and Creutzfeldt-Jakob Depression; primary or metastatic brain tumours; subdural hematoma (usually acute presentation); hyper-/hypothyroidism; vitamin-nutrient deficiency; uremia/renal; hepatic; hyponatremia; autoimmune: vasculitis; end-stage multiple sclerosis; infectious: HIV; syphilis; Lyme disease; varicella-zoster virus; prion Drug-alcohol interactions, medications, and addiction DETECTION & INTERPRETATION OF DIAGNOSIS Neuropsychological testing to establish independent decision-making in cases of unusual symptoms, youth, hazy presentation, or other factors Initial examinations (lab, imaging) To help rule out alternative dementia-causing factors Homocysteine level, a complete blood count with differential, thyroid function, syphilis tests, lipid panel, and vitamin B12 are all included in a chemistry panel. ESR, HIV, folate, C-reactive protein, and HbA1c are special factors to take into account. Biomarkers used in imaging There are various professional standards; they could reveal dementia's root cause. If MRI is not an option, think about a computed tomography (CT) scan instead. Initial AD examination; recent or rapid decline; age 65; stroke history; unusual presentation; worry for malignancy; high bleeding risk - Positron emission tomography (PET) and single-photon emission CT (SPECT): rarely indicated; inadequate data to utilise alone Tests in the Future & Special Considerations Consider genetic testing if you're worried about familial and autosomal dominant AD. Cerebrospinal fluid biomarker testing is not yet recommended. GENERAL TREATMENT MEASURES Optimise the management of comorbid illnesses (such hearing disorders) and risk factors. Planning for advanced care before a person loses the capacity to make independent decisions Evaluate carer exhaustion and support. ALERT In its Choosing Wisely statement, the American Geriatrics Society advises "Don't prescribe cholinesterase inhibitors (ChEIs) for dementia without periodic assessment for perceived cognitive benefits and adverse gastrointestinal effects". First Line: MEDICATION Acetylcholinesterase inhibitors (ChEIs) are most beneficial in mild to moderate disease; they may also be effective in Lewy body dementia. GI issues as well as additional adverse effects like bradycardia and syncope Try a different ChEI if there is no benefit. - When administered for at least 6 months, may produce a mild benefit in cognition and behaviour. Start with 5 mg/day PO of donepezil (Aricept), and if necessary, increase to 10 mg/day after a month and 23 mg/day after three months. - Orally dissolving pills; available in generic - Digoxin and -blockers should be used cautiously (donepezil may lengthen the PR interval). - Capsule, solution, or patch (reduced side effects) for rivastigmine (Exelon): Start at 1.5 mg PO BID, increase by 1.5 mg BID every two weeks, and maintain at 6 to 12 mg/day overall. - Galantamine (Razadyne) tablets, solution, extended-release (ER) capsules, and transdermal formulations: Start at 4 mg BID for 4 weeks, then increase by 4 mg BID every month to reach a dose of 16 to 24 mg/day. Vitamin E: 2,000 IU per day, inconsistent results, potential negative effects Memantine, an NMDA receptor antagonist, is used to treat moderate to severe Alzheimer's disease (AD). - Acetylcholinesterase inhibitors alone or in conjunction with other therapies (2)[A] - Memantine instant release: 5 mg daily; titrate to 10 mg BID, increasing 5 mg per day per week as needed. Memantine ER: 7 mg/day to 28 mg/day with an additional 7 mg/day qwk PRN A monoclonal antibody treatment called Aducanumab (Aduhelm) that targets beta-amyloid. limited benefit and some adverse effects. advise against frequent use; have doctors who specialise in AD evaluate aducanumab Consider second-line treatment for moderate to severe neuropsychiatric symptoms; check for delirium and treatable reasons (sleep hygiene, hearing, environment alterations). Next Line Selective serotonin reuptake inhibitors (SSRIs) are chosen for treating moderate to severe depression. Drugs for insomnia in AD are not very effective at getting people to sleep. - Seniors should not take antihistamines. Risperidone, trazodone, and sleep aids (such as zolpidem) should be used with caution and at the lowest effective doses. If you are experiencing moderate agitation, anxiety, or restlessness, you may want to investigate SSRIs (citalopram) or low-dose risperidone. Careful low-dose risperidone administration for severe psychosis Safety measures - When feasible, stay away from anticholinergic medication. – The use of benzos may result in paradoxical excitement or afternoon sleepiness. - Halcion, a brand name for triazolam, can cause confusion, memory loss, and psychotic behaviour. - Donepezil: use with caution if you have a history of peptic ulcers, sick sinus syndrome, or anticholinergics QUESTIONS FOR REFERENCE If an AD patient has behavioural problems and needs to take psychotropic drugs, think about referring them to geriatric psychiatry. Exercise to relieve restlessness; cognitive stimulation therapy; consider occupational, music, scent, and pet therapy as additional modalities. CONTINUING CARE AFTERCARE RECOMMENDATIONS patient observation Each visit's medication reconciliation, including OTCs Encourage a healthy lifestyle, including physical activity, a balanced diet, enough sleep, social interaction, and mental stimulation. Warn consumers against unproven items that claim to enhance brain function, such as some drugs, dietary supplements, and brain games. Continually evaluate the effectiveness and negative effects of medications (ChEIs/memantine). Late AD might call for placement in skilled care. Medicare will pay for advanced care planning. Assessment of safe driving by the National Highway Traffic Safety Administration: https://www.nhtsa.gov/older-drivers/driving-safely-while-aging-gracefully EDUCATION OF PATIENTS Alzheimer's Association website: www.alz.org Early advanced care planning, including financial preparation, carer assistance, and advanced directives PROGNOSIS Initial diagnosis is frequently delayed, and the average survival time after diagnosis is 4 to 8 years. COMPLICATIONS Include anger, agitation, stumbling, falls, "sundowning," depression, and suicide. Infections, insufficient water or nutrition, and medication toxicity
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