Chairperson - Prof M A Hayee Presenter - Dr. Khurshida Khanam Almi Dr. Md. Shariful Alam
Brief History of Dementia
A woman in her early 50s was admitted to a hospital because of increasingly odd behavior. Her family reported that she had been showing memory problems and strong feelings of jealousy. She also had become disoriented at home and was hiding objects. During a doctor's examination, the woman was unable to remember her husband's name, the year, or how long she had been at the hospital. She could read but did not seem to understand what she read, and she stressed the words in an unusual way. She sometimes became agitated and seemed to have hallucinations and irrational fears.
This woman, known as Auguste D., was the first person reported to have the disease now known as Alzheimer's disease * (AD) Alois Alzheimer German Neuropathologist Auguste D.- 1 st A D Patient Brief History of Dementia US PRESIDENT RONALD REGAN FORMER PRESIDENT DR. IAS UDDIN AHMED They are suffered from Dementia but, What about you?
So, lets know about Dementia What is Dementia? Dementia: It is defined as an acquired persistent and progressive decline in intellectual function that is severe enough to compromise social or occupational functioning.
Key points of Dementia Key points: Impairment of multiple domains of cognitive functions: Memory impairment - Must----- a. New material learning b. Forget previous learning With at least one of the following cognitive disturbance: i. Aphasia-language disturbance ii. Apraxia - impaired ability to carry out motor activities despite intact motor function iii. Agnosia - failure to recognize/ identify familiar object despite intact sensory function iv. Disturbence in executive functions Significant impairment of social & occupational functioning- decline from previous level
Gradual onset, continuing cognitive decline with alert & normal arousal. Epidemiology The prevalence of dementia has been estimated to be approximately 5.7% in over 65 years old.
O The prevalence rate of Alzheimers Disease (AD) for population over 65 years old range from 5-7 per cent for moderately or severely affected people. O Prevalence rate approximately double with every additional 5 years of age from about 1 percent at 65, rising to about 8-10 per cent at age 80 and 30-40 per cent at age 90 years.
There are currently an estimated 18 million people in the world with dementia. This figure is expected to rise dramatically to 34 million by the year 2025. The increase will be greatest in developing countries.
Prevalence of Dementia in Bangladesh
Bangladesh
+ No exact epidemiological data + Incidence 54/100000/year + Peak age 54 yrs.
Hasan M, Khan B Risk Factors for Dementia Non Modifiable Age: 60-70 years Learning Disability: Downs syndrome Gender: AD- F>M, VaD-M>F Genotype: Autosomal dominant form, mutations in the amyloid precursor protein, presenilin 1 and presenilin 2 genes Family history of dementia
Risk Factors for Dementia (CONT..)
O Alcohol consumption O Smoking O Obesity O HTN O Heart diseases : AF, IHD O DM O Stroke
O Hypercholesterimia O Head Injury O Low foliate and raised homocysteine levels O Hormone Replacement therapy O Depression O NSAID Use O Low educational status and mental stimulation Potentially modifiable risk factors
Classification of Dementia Classification of Dementia Primary degenerative dementia - Cognitive impairment is the major presenting features
Dementia plus Syndrome (Secondary) - Cognitive impairment just one face of more wide spread disorder
Vascular dementia is the second most common cause of dementia in the United States and Europe, but it is the most common form in some parts of Asia.
Vascular dementia Vascular dementia is the onset of cognitive impairment, that with a stepwise deteriorating course and a patchy distribution of neurologic deficits caused by cerebrovascular disease.
The prevalence rate of dementia is 9 times higher in patients who have had a stroke than in controls. One year after a stroke, 25% of patients develop new-onset dementia. Within 4 years following a stroke, the relative risk of incident dementia is 5.5%.
Types of Vascular dementia = Many subtypes of vascular dementia have been described to date. The spectrum includes
1) Multi-infarct dementia, 2) Binswanger disease, 3) Mild vascular cognitive impairment, 4) Vascular dementia due to a strategic single infarct, 5) Vascular dementia due to lacunar lesions, 6) Vascular dementia due to hemorrhagic lesions, 7) Subcortical vascular dementia, and 8) Mixed dementia (combination of AD and vascular dementia).
Vascular dementia (CONT..) In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets. Pathologically, multiple small infarcts are observed in the white matter, thalamus, basal ganglia, and pons.
Vascular dementia (CONT..) In single-infarct dementia, different areas in the brain can be affected, which may result in significant impairment in cognition. This may be observed in cases of anterior cerebral artery infarct, parietal lobe infarcts, thalamic infarction, and cingular gyrus infarction. Vascular dementia (Pathophysiology) g Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis.
Fig: Lacunar Disease (Thalamic Inf.) Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. These lacunae are found more typically in the internal capsule, deep gray nuclei, and white matter. Vascular dementia (Pathophysiology) Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. Here vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.
g In cerebral amyloid angiopathyassociated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. In hereditary cystatin-C amyloid angiopathy, patients have recurrent cerebral hemorrhages before age 40 years that can lead to dementia.
g Other less common syndromes which may lead to vascular dementia- Rare arteriopathies such as, inflammatory arteriopathy (eg, polyarteritis nodosa, temporal arteritis) and noninflammatory arteriopathy (eg, moyamoya disease, fibromuscular dysplasia) can cause multiple infarcts and can lead to vascular dementia.
Hypoperfusion due to large vessel or cardiac disease can affect the watershed areas of the brain and lead to vascular dementia. Evaluation of the patient with Dementia Evaluation of the patient with Dementia Early diagnosis helps to prevent the condition from deteriorating. The following are the steps involved in the diagnosis of dementia.
Medical History A detailed family history is gathered from family, friends and colleagues. This helps to gather more information about signs and symptoms, general health, diet, nutrition and alcohol intake.
Neurological Examination This is done to assess proper functioning of the nervous system. This involves tests for reflexes, coordination and balance, muscle tone and strength, eye movement, speech and sensation.
Mini-Mental State Examination (MMSE) This involves a questionnaire about day-to-day routine activities to access the mental function.
Psychiatric evaluation Is necessary to find out the nature of the disorder such as depression or any other psychiatric disorder. Evaluation of the patient with Dementia Basic Medical Tests This includes:
Routine laboratory tests Occasionally helpful tests Thyroid function (TSH) Parathyroid function Vitamin B 12 Adrenal function Complete blood count Urine heavy metals Electrolytes RBC sedimentation rate Angiogram Brain biopsy Optional focused tests Psychometric testing Chest X-ray Lumber puncture Liver function Renal function Urine toxin screen HIV Apolipoprotien E RPR or VDRL
Brain Imaging Brain scans like structural imaging (CT/MRI), functional imaging Electroencephalogram (EEG), single photon-emission computed tomography (SPECT) are done to identify the changes in brain structure and function. The Mini-Mental Status Examination Points Orientation Name: season/date/day/month/year 5 (1 for each name) Name: hospital/floor/town/state/country 5 (1 for each name)
Registration Identify three objects by name and ask 3 (1 for each name) patient to repeat
Attention and calculation Serial 7s; subtract from 100 (e.g., 93-86-70-72-65) 5 (1 for each name) Recall Recall the three objects presented earlier 3 (1 for each name)
Language Name pencil and watch 2 (1 for each name) Repeat No ifs, ands, or buts 1 Follow a 3-step command (e.g, Take this paper, fold 3 (1 for each name) it in half, and place it on the table) Write close your eyes and ask patient to obey 1 written command Ask patient to write a sentence 1 Ask patient to copy a design 1
Total 30 Interpretation of MMSE 27-30 = normal 25-26 = possible 10-24 = mild-moderate 6-9 = mod-severe <6 = severe
Prognosis Vascular dementia is associated with a higher mortality rate than AD, presumably because of the coexistence of other atherosclerotic diseases.
The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls.
Study on causes showed that circulatory system disorders (eg, ischemic heart disease) is the most common immediate cause of death in vascular dementia, followed by respiratory system diseases (eg, pneumonia).
The prognosis for MID is usually not very promising. Even though it may seem that people with MID improve over time, their condition often steadily declines after ensuing silent strokes.
Complications of Dementia ; Abuse by an overstressed caregiver. ; Increased infections anywhere in the body. ; Loss of ability to function or care for self. ; Loss of ability to interact. ; Reduced life span. ; Side effects of medications used to treat the disorder.
Strategies for Medical Treatment of Dementia
+ Prevention of disease + Delay of onset + Slow rate of progression + Treat primary symptoms (cognitive) + Treat secondary symptoms (behavioral) Prevention As there is no definite cure till now for dementia but we can reduce the risk by leading an active life with healthy practices.
Healthy practices include: O Avoiding alcohol, smoking and drug abuse. O Healthy diet with low in saturated animal fat. O Using seat belts when driving. O Wearing helmets when riding motor cycles. O Wearing protective headgear when playing contact sports
Treatment of Dementia
Pharmacotherapy: The following drugs are used- Cholinesterase Inhibitors Cholinesterase inhibitors are drugs that block the activity of an enzyme in the brain called cholinesterase. The drugs that come under this class are Tacrine, Donepezil, Rivastigmine, Galantamine or Galanthamine.
Antidepressants or Anxiolytics Antidepressants are a group of drugs used to alleviate depression. Anxiolytics are drugs that are used to treat anxiety and depression. The drugs coming under this group are Fluoxetine, Sertraline, Paroxetine and Citalopram.
Antipsychotics Antipsychotics are a group of drugs used to treat psychosis. Haloperidol, Risperidone, Quetiapine, Olanzapine, Ziprasidone are the drugs under this class.
Anticonvulsants These are also called antiepileptic drugs and are used in the prevention of occurrence of epileptic seizures. Valproic acid, Carbamazepine Gabapentin, Lamotrigine.
Over-the-counter (OTC) drugs The available OTC drugs for dementia are Diphenhydramine and nonsteroidal antiinflammatory drugs (NSAIDs) like Aspirin, Naproxen, or Ibuprofen. Treatment of Dementia (CONT..) Alternate Treatment: Reminiscence Therapy This involves discussing about the past events in groups and helping them to recall using photos or familiar objects.
Reality Orientation Helping the patient to remember where he or she is and letting them know what is going around them.
Vitamin and Other Supplements - VitaminB12 and folic acid, lower the levels of an amino acid in the blood that is usually high in Alzheimers patients. - Zinc can improve memory, which lacks in elderly people. - L-arginine, an amino acid increase the blood flow in the brain helping vascular dementia. - Alpha-linolenic acid (ALA), borage oil and evening primrose oil containing essential fatty acids may help to reduce the risk of Alzheimers disease. - A diet including less animal fats and more fish is helpful.
Treatment of Dementia (CONT..) Future possible therapies under evaluation: Glycogen syntehtase kinase 3 (GSK 3) -secretase inhibitors -secretase inhibitors -secretase enhancers Overview of Anti-cholinesterase Inhibitors Oldest (and probably most extensively tested): Physostigmine
O Obsolete because- very short lasting (half life 30 mints) necessitating frequent oral administration O Potentially serious dose-limiting S/E
In the past: Tacrine O Again S/E; 50% of the patients treated with tacrine discontinued treatment because of adverse events esp. hepatotoxicity.
Overview of ACHE Inhibitors (CONT..) Recent past: Donepezile O Launched in the USA in January 1997 and in the UK in March 1997 O Modest benefits in terms of cognition O Most common S/E are similar to those seen with tacrine
Very Recent: Rivastigmine O Launched in the USA in April 2000; received approval for use in 60 countries including all member states of EU and USA O Improvements were seen in cognition, ADL & severity of dementia O Dose of 6-12 mg/day O Lower risk of adverse effects
Exelon Patch (Rivastigmine)
Advantages of new Exelon Patch s Easy to apply s Reduce patients pill burden s Reduce care givers distress s Achieve optimal therapeutic dose s Dramatically improved GI Tolerability s Ensures Continuous & Consistent drug delivery that results fewer side effects & Improved efficacy
Dosage guideline for newly diagnosed patient Exelon Patch-5 Exelon 4.6 mg/24 h Patch Starting dose
4 weeks One-step dose increase
Exelon Patch-10 Exelon 9.5 mg/24 h Patch Target dose
Switching from other therapy Patient on other medication e.g., Donepezil. First Stop the drug then Exelon Patch-5 Exelon 4.6 mg/24 h Patch Starting dose
4 weeks One-step dose increase
Exelon Patch-10 Exelon 9.5 mg/24 h Patch Target dose
Exelon Patch: Where to apply? Exelon Patch can be applied to: O Upper or lower back O Upper arm O Chest When replacing the patch, the new patch should be applied to a different spot of skin O Do not use the same spot more than once every 14 days Normal daily activities, such as bathing, are permitted