​Kembara Xtra - Medicine - Dementia

​Kembara Xtra - Medicine - Dementia 
Introduction 
The term "dementia" refers to a cognitive deterioration from a prior level of performance in several different cognitive domains (attention, executive function perceptual-motor, social cognition, language, and memory), which interfere considerably with ADLs in the absence of delirium or any other mental disease.
According to the DSM-5, dementias are classified as neurocognitive disorders (major and moderate), and the following factors are specified as the causes of neurocognitive deterioration related to dementia: – Alzheimer dementia (AD) – Vascular dementia (VaD) – Lewy body dementia – Parkinson disease dementia – Frontotemporal dementia – Creutzfeldt-Jakob disease (CJD) – HIV dementia – Substance-/medication-induced neurocognitive disorder

Incidence according to Epidemiology In 2011, the average yearly incidence of Alzheimer's disease was 0.4% in people aged 65 to 74, 3.2% in people aged 75 to 84, and 7.6% in people aged 85 and above.
It is anticipated that the annual incidence of Alzheimer's disease and other dementias would double by the year 2050.

Prevalence
Alzheimer's disease was found in 11.3% of patients older than 65 years old (5.3% of those aged 65 to 74, 13.8% of those aged 75 to 84, and 34.6% of those aged 85 and above). 1.6% for VaD; 13% for all other causes
It is anticipated that the number of people living in the United States who have dementia will rise to 14 million by the year 2050.


Causes and effects: etiology and pathophysiology 

 Alzheimer's disease is characterized by the deposition of beta-amyloid protein and/or neurofibrillary tangles (NFTs), dysfunctional synapses, neurodegeneration, and ultimately the death of neurons.  The accumulation of beta-amyloid and/or the rate of progression toward the clinical signs of Alzheimer's disease may be influenced by age, genetics, systemic disease, smoking, and other host factors. Vascular dementia refers to cerebral atherosclerosis or emboli with clinical or subclinical infarcts. Genetics
AD: positive family history in 50%, but 90% of AD is sporadic: APOE4 enhances risk, but full role unclear. Amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2) account for 5% of AD. APOE4 increases risk but full function unclear.

factors of danger 

The most important consideration is one's age.
● Sex: female > male ● Genetic predisposition
● Hypertension: AD; VaD
Hypercholesterolemia, also known as AD and VaD

● Diabetes: VaD
Obesity: Vascular Artery Disease
● Cigarette smoking: VaD
endocrine and metabolic disorders such as hypothyroidism and Cushing syndrome; deficiencies in thiamine and vitamin B12; chronic alcoholism and other drug use 
a lower educational position, an early-life head injury, and a sedentary lifestyle are risk factors for Alzheimer's disease.

Preventive Measures in General 

• Undergo treatment for reversible causes of dementia, such as vitamin deficiencies, drug-induced dementia, and alcohol-induced dementia.
Diabetes, hypertension, and hypercholesterolemia should all be treated.
There is no evidence to suggest that statins or any other single drug can delay or prevent the onset of dementia.

● BP management and low-dose aspirin may prevent or lessen cognitive deterioration in VaD.
Continue engaging in mentally challenging activities as well as social connections, and either keep up with or ramp up your level of physical activity and exercise.

Anxiety disorders and serious depressive disorders are associated with this.
Psychosis (delusions; delusions of persecution are prevalent); Delirium; Behavioral problems (agitation, violence); Sleep disturbances; Psychotic symptoms include:


Providing an Account of History 

It is necessary to have a member of the patient's family or another person who is familiar with them well report changes in the patient's cognition and conduct.
● Probable diagnosis AD: - An age range between 40 and 90 years, with an average of over 65 years.
- A gradual loss in cognitive ability with an indirect onset
– Deficits in areas of cognition – No other explainable cause of symptoms – There are no conscious disturbances – There are cognitive deficits
- It is important to rule out specific conditions such as depression, bereavement reaction, vitamin B12 deficiency, and thyroid illness.
- One of the supporting variables is a history of dementia in the family

The Patient's Clinical Examination 
Clinical Assessment
Physical exam to evaluate for neurologic deficits, motor and gait abnormalities, tremors, and other symptoms No disturbances of consciousness Able to begin with brief initial screening tests for cognitive impairment The Mini-Cog test, also known as the General Practitioner Assessment of Cognition, is used to diagnose dementia. 8-item Informant Questionnaire

 If the screening reveals a positive result, the individual should also undergo screening for depression (using instruments like the PHQ-2 and PHQ-9, as well as the geriatric depression scale), and other cognitive evaluation tools may be used if necessary.
Deterioration of cognitive abilities as measured by standardized instruments, which may include the following: – The Mini-Mental State Examination (MMSE) – The Montreal Cognitive Assessment (MoCA) test – The Adult Dementia Assessment Scale for Cognitive Impairment (ADAS-Cog) – Caution should be exercised when relying exclusively on cognition ratings, particularly in the case of individuals who have trouble learning, language problems, or other such constraints.
Neuropsychological testing is detailed evaluation of several cognitive areas, and it can help differentiate between normal aging and dementia by providing this information. This may be helpful in challenging cases in which the patient's history and mental status examination do not agree, and it is most valuable when it is repeated over the course of treatment.


Differential diagnosis includes major depression, medication side effects, chronic alcohol use, delirium, subdural hematoma, normal pressure hydrocephalus, brain tumor, thyroid disease, Parkinson disease, vitamin B12 deficiency, and toxins (including aromatic hydrocarbons, solvents, heavy metals, marijuana, opiates, and sedativehypnotics).

Initial Tests (lab, imaging)
Used for excluding potential causes
– Complete blood count, complete metabolic profile, thyroid stimulating hormone, vitamin B12 level Select patients based on clinical suspicion – HIV, rapid plasma reagin (RPR), and vitamin B12 level 
- The erythrocyte sedimentation rate, often known as the ESR
- Screening for heavy metals and toxicity using folate
Decreased levels of beta-amyloid (1 to 42) and increasing levels of beta and p-amyloid are distinguishing characteristics of Alzheimer's disease (AD), as proven by research investigations utilizing cerebrospinal fluid (CSF) biomarkers in patients with confirmed Alzheimer's disease. In contrast, levels of CSF beta proteins are elevated in Creutzfeldt-Jakob disease (CJD).
Neuroimaging (CT/MRI of the brain): - Routine neuroimaging, which is generally suggested when evaluating for dementia, can aid to distinguish particular kinds of dementia with structural imaging findings. - Neuroimaging (MRI/CT) to rule out other potential causes if the onset of symptoms occurred at a young age (less than 65 years), the development was rapid, focal neurologic impairments were present, or atypical symptoms were present. Important Findings Regarding Alzheimer's Disease: Diffuse Cerebral Atrophy Beginning in Association Areas, Hippocampus (Atrophy of the Hippocampus May Be the Earliest Symptom), and Amygdala - Vascular arterial disease: previous infarcts, especially lacunar

Additional Examinations, as well as Other Important Factors
Genetic testing for dementia, such as testing for APOE4 for Alzheimer's, is not indicated until there are several family members diagnosed with AD at a young age. This is the case even when testing for Alzheimer's.
In the case of atypical presentations, an LP and CSF study should be considered in order to determine whether infectious, inflammatory, or neoplastic etiologies are present.
PET scan is not commonly indicated but has been cleared to identify between Alzheimer disease and frontotemporal dementia. Diagnostic Procedures/Other


Management Occupational training and a structured physical exercise program Sensory stimulation (display of clocks and calendars) in the early to middle stages Discussion with the family concerning support and advance directives Management Daily schedules and written directions Emphasis on nutrition, personal hygiene, accident-proofing the home, safety issues, sleep hygiene, and supervision Socialization (adult daycare)

The relationship between medication and cognitive impairment
Medications for Alzheimer's disease (AD) indicate a minor improvement in some cognitive tests, but it is yet unknown whether or not this improvement is clinically significant and whether or not it is accompanied with any negative effects.
Cognitive dysfunction, mild – Cholinesterase inhibitors: donepezil (Aricept), 5 to 10 mg/day; rivastigmine (Exelon), 1.5 to 6.0 mg BID, transdermal system 4.6 mg/24 hr and 9.5 mg/day; galantamine (Razadyne), 4 to 12 mg BID, extended release 8 to 24 mg/day Adverse events: nausea, vomiting, diarrhea, anorexia, nightmares  Caution should be exercised when using galantamine because it has been linked to death in patients with mild cognitive impairment in clinical trials. Patients who have been diagnosed with mild to severe dementia (MMSE 10 to 26) are encouraged to give cholinesterase inhibitors serious consideration. Responses may be highly variable.
 Begin treatment with the medication that has the cheapest acquisition cost; in addition, take into account its adverse event profile, adherence, medical comorbidity, drug interactions, and dose profiles.
cholinesterase inhibitors, memantine (Namenda), an NMDA receptor antagonist, 5 to 20 mg per day Cognitive dysfunction that is mild to severe cholinesterase inhibitors, memantine (Namenda), an NMDA receptor antagonist Adverse events: dizziness, confusion, headache, constipation
In patients with moderate to advanced dementia (MMSE 17), the recommendations are to add memantine (10 mg BID) to a cholinesterase inhibitor, or to use memantine alone in patients who do not tolerate or benefit from a cholinesterase inhibitor. Memantine is generally well tolerated and has fewer side effects in comparison to cholinesterase inhibitors.
It is recommended that patients using memantine who have severe dementia (MMSE score of ten or lower) continue taking the medication. However, when dementia has reached an advanced stage, it may be possible to stop taking drugs in order to improve the patient's quality of life and comfort.
- Different pharmaceuticals
 Aducanumab (Aduhelm) is a recombinant monoclonal antibody against beta-amyloid that has been approved by the FDA for the treatment of mild Alzheimer's disease but is only used in research settings.
 There has been a lack of consistency in the clinical benefits observed in trials.
Conditions that are commonly connected with psychosis, such as agitation and aggressive behavior:
 Investigate potential triggering factors, such as infections, pain, sadness, or medications.
It is recommended that nonpharmacologic treatments (such as behavioral interventions, music therapy, and so on) be used first as a form of treatment.
Mood stabilizers such as valproic acid and carbamazepine have been utilized, despite the lack of evidence to support their use.
 Antipsychotics are recommended for moderate to severe symptoms.
Initiate low dosages, risperidone 0.25 to 1.00 mg/day; olanzapine 1.25 to 5.00 mg/day; quetiapine 12.5 to 50.0 mg/day; aripiprazole 5 mg/day; ziprasidone 20 mg/day Because it has less extrapyramidal adverse effects than other atypical antipsychotics, quetiapine is frequently the first medication used.
 It has been demonstrated that the novel antipsychotic pimavanserin (selective 5-HT2A receptor inverse agonist) is an effective treatment for Parkinson disease psychosis, and it does so with a little risk of decreasing motor function, in contrast to existing treatments (5).[B].
ALERT
Warnings in the black box about antipsychotics because of an increased risk of death in the elderly with dementia

Considerations Regarding the Aged
Start medication at modest doses and gradually increase them if higher doses are required later on.
Despite the fact that there is evidence suggesting that older persons should not take benzodiazepines, the medication is still widely used.
ALERT
A higher risk of falling is observed in patients who use benzodiazepines.

 Keep an eye out for a decline in both your renal function and your hepatic metabolism.
First Line
Modifications to the environment, training for caregivers, exercise, music therapy, and pet therapy are examples of nonpharmacologic treatments. 
Two-Thirds Line

Inhibitors of cholinesterase, memantine, atypical antipsychotics, antidepressants, mood stabilizers, methylphenidate, benzodiazepines, and melatonin are all examples of medications that fall under this category. 
There is not enough evidence to conclude that antidepressants are more effective than a placebo in treating depression (HTA-SADD).


Referral Concerns Neuropsychiatric evaluations can be helpful in the early stages or for patients with modest cognitive impairment.

Extra Medical Interventions 

behavioral modification Socialization, such as adult daycare, to prevent loneliness and depression Sleep hygiene program as an alternative to medicines for sleep disturbance Scheduled toileting to prevent incontinence behavioral modification 

Admission

It is possible that admission to a psychiatric facility will be necessary due to concerns regarding the patient's safety (self-harm or danger to others), self-neglect, aggressive tendencies, or other behavioral difficulties.

Continued Patient Observation and Monitoring

 Adverse events of pharmacotherapy Nutritional status Caregiver evaluation of stress Advance care planning: Discuss safety, management of finances, medical decision making, and possible skilled facility placement; legal guardianship, if necessary Advance directives, health care proxy, and other forms of advance care planning should be emailed. Progression of cognitive impairment by using a standardized tool (such as the MMSE or the ADAS-Cog). Development of behavioral problems


The progression of Alzheimer's disease is often slow and constant, and it eventually causes severe cognitive impairment. Around 10 years is the typical amount of time a person can live with AD.

 Secondary dementias: treatment of the underlying ailment may lead to improvement; usually encountered with normal pressure hydrocephalus, hypothyroidism, and brain tumors. Dementia with vascular amyloid angiopathy (DVA): dementia that gets progressively worse over time, and cognitive improvement is quite unlikely. 
Patients who are in the later stages of dementia may benefit from receiving paliative care or hospice treatment.

Complications 
● Wandering

 Sundowner syndrome is widespread in elderly patients (because they are sedated), as well as in dementia patients (who can have a negative reaction to even a tiny amount of psychoactive medications).
Injuries sustained from falls, including a broken hip, head injuries, and hematomas
Neglect and abusive treatment
Burnout among caregivers, which may be treated with respite care and by the participation in support groups