Alzheimer Disease, Lewy Body, and Parkinson Dementia
Alzheimer Disease, Lewy Body, and Parkinson Dementia
Neurocognitive disorder caused by AD (NCD due to AD) is a slow developing nonreversible brain disorder that results in a permanent loss of neurons and neuronal synapses. The loss of neurons is prevalent in the areas of the brain responsible for memory, function, and cognition. Neuronal destruction comes from extracellular neuritic plaque and neurofibrillary tangles inside neurons. Acetylcholine, which enables learning and memory, is also decreased.
NCD due to AD is gender neutral (Table 3). Family history and age increase the risk of developing NCD due to AD. The risk for an individual with a parent or sibling with NCD due to AD increases as much as 30% with each afflicted family member. Age increases risk exponentially. Individuals 65 to 69 years old have an incidence rate of about 10 per 1,000 persons, doubling at each 5-year increment. After 85 years of age, the incidence of NCD due to AD is approximately 85 per 1,000 individuals.
NCD due to AD delineates that mild or major NCD must have an insidious onset with gradual progression. NCD with AD is classified into 4 categories: (1) possible major NCD due to AD, (2) probable major NCD due to AD, (3) possible mild NCD due to AD, or (4) probable mild NCD due to AD.
Major NCD Due to AD. Major NCD due to AD must meet 2 criteria. The first criterion is the presence of a genetic mutation or a positive family history. The second criterion consists of 3 subcategories, all of which must be met: (1) a decline in memory and learning plus 1 other cognitive domain (Table 1), (2) insidious and gradual presentation with possible brief plateaus, and (3) no mixed etiology (eg, cerebrovascular accident and sepsis). A major "probable" diagnosis is given when both 1 and 2 are present and "possible" when either criterion 1 or 2 is met.
Mild NCD Due to AD. Mild NCD due to AD also has probable and possible designations (Table 2). "Probable" mild NCD due to AD is diagnosed when there is a genetic mutation or family history. "Possible" mild NCD due to AD is diagnosed when no genetic mutation or family history exists and all of the following are present: evidence of memory and learning decline, gradual and insidious onset without extended plateaus, and no evidence of mixed etiology.
In addition to these criteria, clinical manifestations of mild NCD due to AD can include executive dysfunction (eg, difficulty paying bills or playing an instrument). Individuals with NCD due to AD may exhibit manifestations such as visual spatial or visual perception disturbances or motor and language deficits in moderate to severe disease. Social skills usually remain intact until late in the trajectory. In the severe stage, muteness, gait disturbances, incontinence, and complete dependence may result.
Pharmacologic treatment of NCD due to AD includes 2 classes of pharmacologic treatment: cholinesterase inhibitors (CEIs) and N-methyl-D-aspartic acid receptor antagonists. The administration of CEIs decreases the destruction of acetylcholine, improving acetylcholine levels available within the neuronal synapse, and may help with memory and learning. Although CEIs do not stop the disease trajectory, they may slow the decline.
The CEIs are the first line of treatment for mild NCD due to AD. There are 3 CEIs currently on the market, donepezil, galantamine, and rivastigmine, which can help ameliorate behavioral symptoms, such as anxiety, depression, hallucinations, or agitation for 6 to 12 months. Memantine, an N-methyl-D-aspartic acid receptor antagonist, is approved in combination with a CEI for moderate to severe stages. It is thought to protect neuronal function and possibly slow the progression of AD.
Controversy remains over when to stop medication. It is recommended that medications be given until the individual is in the final stages and a rapid decline will not impact the quality of life. Evidence of accelerated decline, often seen with discontinuation of dementia medication, may include adverse mood changes such as aggression, paralytic ileus, aspiration, and death. Emotional and ethical components should guide the final decision, taking into account the individual's and family's wishes and the clinical judgment of the provider. The most common cause of death in the late stage of dementia is aspiration. Research is needed to determine guidelines for the most appropriate time to discontinue medications.
Neurocognitive Disorder Caused by AD
Neurocognitive disorder caused by AD (NCD due to AD) is a slow developing nonreversible brain disorder that results in a permanent loss of neurons and neuronal synapses. The loss of neurons is prevalent in the areas of the brain responsible for memory, function, and cognition. Neuronal destruction comes from extracellular neuritic plaque and neurofibrillary tangles inside neurons. Acetylcholine, which enables learning and memory, is also decreased.
Risk Factors
NCD due to AD is gender neutral (Table 3). Family history and age increase the risk of developing NCD due to AD. The risk for an individual with a parent or sibling with NCD due to AD increases as much as 30% with each afflicted family member. Age increases risk exponentially. Individuals 65 to 69 years old have an incidence rate of about 10 per 1,000 persons, doubling at each 5-year increment. After 85 years of age, the incidence of NCD due to AD is approximately 85 per 1,000 individuals.
Diagnostic Criteria
NCD due to AD delineates that mild or major NCD must have an insidious onset with gradual progression. NCD with AD is classified into 4 categories: (1) possible major NCD due to AD, (2) probable major NCD due to AD, (3) possible mild NCD due to AD, or (4) probable mild NCD due to AD.
Major NCD Due to AD. Major NCD due to AD must meet 2 criteria. The first criterion is the presence of a genetic mutation or a positive family history. The second criterion consists of 3 subcategories, all of which must be met: (1) a decline in memory and learning plus 1 other cognitive domain (Table 1), (2) insidious and gradual presentation with possible brief plateaus, and (3) no mixed etiology (eg, cerebrovascular accident and sepsis). A major "probable" diagnosis is given when both 1 and 2 are present and "possible" when either criterion 1 or 2 is met.
Mild NCD Due to AD. Mild NCD due to AD also has probable and possible designations (Table 2). "Probable" mild NCD due to AD is diagnosed when there is a genetic mutation or family history. "Possible" mild NCD due to AD is diagnosed when no genetic mutation or family history exists and all of the following are present: evidence of memory and learning decline, gradual and insidious onset without extended plateaus, and no evidence of mixed etiology.
Clinical Manifestations
In addition to these criteria, clinical manifestations of mild NCD due to AD can include executive dysfunction (eg, difficulty paying bills or playing an instrument). Individuals with NCD due to AD may exhibit manifestations such as visual spatial or visual perception disturbances or motor and language deficits in moderate to severe disease. Social skills usually remain intact until late in the trajectory. In the severe stage, muteness, gait disturbances, incontinence, and complete dependence may result.
Treatment
Pharmacologic treatment of NCD due to AD includes 2 classes of pharmacologic treatment: cholinesterase inhibitors (CEIs) and N-methyl-D-aspartic acid receptor antagonists. The administration of CEIs decreases the destruction of acetylcholine, improving acetylcholine levels available within the neuronal synapse, and may help with memory and learning. Although CEIs do not stop the disease trajectory, they may slow the decline.
The CEIs are the first line of treatment for mild NCD due to AD. There are 3 CEIs currently on the market, donepezil, galantamine, and rivastigmine, which can help ameliorate behavioral symptoms, such as anxiety, depression, hallucinations, or agitation for 6 to 12 months. Memantine, an N-methyl-D-aspartic acid receptor antagonist, is approved in combination with a CEI for moderate to severe stages. It is thought to protect neuronal function and possibly slow the progression of AD.
Controversy remains over when to stop medication. It is recommended that medications be given until the individual is in the final stages and a rapid decline will not impact the quality of life. Evidence of accelerated decline, often seen with discontinuation of dementia medication, may include adverse mood changes such as aggression, paralytic ileus, aspiration, and death. Emotional and ethical components should guide the final decision, taking into account the individual's and family's wishes and the clinical judgment of the provider. The most common cause of death in the late stage of dementia is aspiration. Research is needed to determine guidelines for the most appropriate time to discontinue medications.
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