Alzheimer’s disease
BASIC INFORMATION
This is the commonest dementia, a degenerative disease of the cortex, accounting for over 65% of dementia in any age group. The cardinal clinical features are:
* progressive loss of ability to learn, retain and process new information (i.e. memory loss)
* decline in language - difficulty in naming and in understanding what is being said (various aphasias)
* apraxia - impaired ability to carry out skilled motor activities
* agnosia - failure to recognize objects, e.g. clothing, places or people
* progressive loss of executive function - organizing, planning and sequencing
* behavioural change - agitation, aggression, wandering and persecutory delusions
* loss of insight, relative or complete
* depression - though severe depression is unusual, perhaps because of loss of insight.
The onset is gradual. Alzheimer’s disease (AD) is rare below the age of 50 but increasingly common thereafter. Disturbance of gait, motor and occasionally sensory abnormalities and seizures occur late. The course is progressive over several to 10 or more years, with death in a state of extreme cognitive decline.
DSM-IV defines Alzheimer’s as follows:
A. The development of multiple cognitive deficits manifested by both:
1. Memory impairment (impaired ability to learn new information and to recall previously learned information)
2. One (or more) of the following cognitive disturbances:
a. Aphasia (language disturbance)
b. Apraxia (impaired ability to carry out motor activities despite intact motor function)
A. The development of multiple cognitive deficits manifested by both:
1. Memory impairment (impaired ability to learn new information and to recall previously learned information)
2. One (or more) of the following cognitive disturbances:
a. Aphasia (language disturbance)
b. Apraxia (impaired ability to carry out motor activities despite intact motor function)
• Recall: patients with early stages of dementia will make first errors in this function, often with no other errors in the examination. Errors in orientation follow next.
• Language: patients with early stages of Alzheimer’s disease will have specific difficulty drawing a clock showing a given time. This is a measure of the characteristic visual-spatial impairment.
• Consider comprehensive neuropsychologic testing by a qualified neuropsychologist to confirm screening mental status testing. This testing can help differentiate parietal-temporal dementias (AD or PD) from frontal-temporal dementias, such as Pick’s, or focal dementias, such as vascular dementias.
DIAGNOSIS
WORKUP
Lumbar puncture if chronic CNS infection is suspected
LABORATORY TESTS
• CBC
• Serum electrolytes
• Glucose
• BUN/creatinine
• Liver and thyroid function tests
• Serum vitamin B12 and methylmalonic acid
• Syphilis serology
• HIV, sedimentation rate, urinalysis
IMAGING STUDIES
CT scan or MRI to rule out hydrocephalus and mass lesions and to document cerebral atropy
TREATMENT
NONPHARMACOLOGIC THERAPY
Patients must have a caregiver; enrollment in adult day care centers is helpful.
ACUTE GENERAL Rx
None
CHRONIC Rx
• Above all, make sure the patient does not have a treatable cause of dementia.
• Estrogen replacement may reduce incidence in women.
• Donepezil (Aricept) 5 mg PO at hs initially, subsequently increased to 10 mg qd may improve both cognition and global function in mild to moderate Alzheimer’s dementia. This drug is very expensive and may not be cost effective. Not indicated in severe Alzheimer’s.
• Rivastigmine (Exelon) is a reversible cholinesterase inhibitor recently approved for the treatment of mild to moderate dementia of Alzheimer’s type. Starting dose is 1.5 mg bid, gradually increasing to 3 mg bid if well tolerated after a minimum of 2 weeks. Not indicated in severe Alzheimer’s.
• Galantamine (Reminyl) is a newer agent for the treatment of mild to moderate dementia of the Alzheimer’s type. Its precise mechanism of action is unknown but is thought to include acetylcholinesterase inhibition. Initial starting dose is 4 mg PO bid. This medication is contraindicated in patients with severe hepatic or renal impairment.
• Language: patients with early stages of Alzheimer’s disease will have specific difficulty drawing a clock showing a given time. This is a measure of the characteristic visual-spatial impairment.
• Consider comprehensive neuropsychologic testing by a qualified neuropsychologist to confirm screening mental status testing. This testing can help differentiate parietal-temporal dementias (AD or PD) from frontal-temporal dementias, such as Pick’s, or focal dementias, such as vascular dementias.
DIAGNOSIS
WORKUP
Lumbar puncture if chronic CNS infection is suspected
LABORATORY TESTS
• CBC
• Serum electrolytes
• Glucose
• BUN/creatinine
• Liver and thyroid function tests
• Serum vitamin B12 and methylmalonic acid
• Syphilis serology
• HIV, sedimentation rate, urinalysis
IMAGING STUDIES
CT scan or MRI to rule out hydrocephalus and mass lesions and to document cerebral atropy
TREATMENT
NONPHARMACOLOGIC THERAPY
Patients must have a caregiver; enrollment in adult day care centers is helpful.
ACUTE GENERAL Rx
None
CHRONIC Rx
• Above all, make sure the patient does not have a treatable cause of dementia.
• Estrogen replacement may reduce incidence in women.
• Donepezil (Aricept) 5 mg PO at hs initially, subsequently increased to 10 mg qd may improve both cognition and global function in mild to moderate Alzheimer’s dementia. This drug is very expensive and may not be cost effective. Not indicated in severe Alzheimer’s.
• Rivastigmine (Exelon) is a reversible cholinesterase inhibitor recently approved for the treatment of mild to moderate dementia of Alzheimer’s type. Starting dose is 1.5 mg bid, gradually increasing to 3 mg bid if well tolerated after a minimum of 2 weeks. Not indicated in severe Alzheimer’s.
• Galantamine (Reminyl) is a newer agent for the treatment of mild to moderate dementia of the Alzheimer’s type. Its precise mechanism of action is unknown but is thought to include acetylcholinesterase inhibition. Initial starting dose is 4 mg PO bid. This medication is contraindicated in patients with severe hepatic or renal impairment.
c. Agnosia (failure to recognize or identify objects despite intact sensory function)
d. Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)
B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.
C. The course is characterized by gradual onset and continuing cognitive decline.
D. The cognitive deficits in criteria A1 and A2 are not a result of any of the following:
1. Other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson’s disease, Huntington’s disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)
2. Systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
3. Substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium.
F. The disturbance is not better accounted for by another Axis I disorder (e.g., major depressive disorder, schizophrenia).
EPIDEMIOLOGY & DEMOGRAPHICS
INCIDENCE (IN U.S.): 3.5% of Americans ages 65 to 74 yr
PREDOMINANT SEX: Female
PREDOMINANT AGE: 85+ yr
PEAK INCIDENCE: 65 to 74 yr
GENETICS: Patients with trisomy 21 (Down syndrome) develop Alzheimer’s in middle age. There is a gene on chromosome 109 that appears to be linked to increased levels of amyloid B42 , a neurotoxic molecule associated with both early-onset and late-onset Alzheimer’s disease.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
Families often bring patient to medical attention because of memory problems (e.g., repetitive questions, misplacement of items, missed appointments, getting lost away from home), hallucinations, disruptive behavior, insomnia, and anxiety/depression disorders. Initial screen of cognitive function: diagnosis requires a documentation of a decline in cognition from a previous level.
• Orientation to time and space: based on intact registration and recall (short-term memory); orientation to space is preserved longer than orientation to time.
• Registration: depends on hearing and paying attention; if patient unable to complete task, consider the diagnosis of delirium.
• Attention and calculation: to avoid educational bias, use simple tasks such as saying the days of the week forward and backward or counting backward from 20 to 0; because this function is preserved very late in Alzheimer’s disease, if patient unable to complete task, consider a frontal lobe dementia such as Pick’s disease or delirium.
d. Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)
B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning.
C. The course is characterized by gradual onset and continuing cognitive decline.
D. The cognitive deficits in criteria A1 and A2 are not a result of any of the following:
1. Other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson’s disease, Huntington’s disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)
2. Systemic conditions that are known to cause dementia (e.g., hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection)
3. Substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium.
F. The disturbance is not better accounted for by another Axis I disorder (e.g., major depressive disorder, schizophrenia).
EPIDEMIOLOGY & DEMOGRAPHICS
INCIDENCE (IN U.S.): 3.5% of Americans ages 65 to 74 yr
PREDOMINANT SEX: Female
PREDOMINANT AGE: 85+ yr
PEAK INCIDENCE: 65 to 74 yr
GENETICS: Patients with trisomy 21 (Down syndrome) develop Alzheimer’s in middle age. There is a gene on chromosome 109 that appears to be linked to increased levels of amyloid B42 , a neurotoxic molecule associated with both early-onset and late-onset Alzheimer’s disease.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
Families often bring patient to medical attention because of memory problems (e.g., repetitive questions, misplacement of items, missed appointments, getting lost away from home), hallucinations, disruptive behavior, insomnia, and anxiety/depression disorders. Initial screen of cognitive function: diagnosis requires a documentation of a decline in cognition from a previous level.
• Orientation to time and space: based on intact registration and recall (short-term memory); orientation to space is preserved longer than orientation to time.
• Registration: depends on hearing and paying attention; if patient unable to complete task, consider the diagnosis of delirium.
• Attention and calculation: to avoid educational bias, use simple tasks such as saying the days of the week forward and backward or counting backward from 20 to 0; because this function is preserved very late in Alzheimer’s disease, if patient unable to complete task, consider a frontal lobe dementia such as Pick’s disease or delirium.
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