Alzheimer’s disease (AD) is the most common cause of dementia in Western countries.
Alzheimer’s disease occurs almost exclusively above the age of 60 and increases with age, affecting approximately 5% of all persons over the age of 70. The course of AD is progressive.
In the early stages of the disease, the memory loss may go unrecognized or may be ascribed to benign forgetfulness. Slowly the cognitive problems begin to interfere with daily activities, such as keeping track of finances, following instructions on the job, driving, shopping, and housekeeping. Some patients are unaware of these difficulties (agnosognosia), and others have considerable insight, resulting in frustration and anxiety. These major differences in insight have no clear explanation.
The most important risk factors for AD are old age and a positive family history. The frequency of AD increases with each decade of adult life to reach 20 to 40% of the population over the age of 85. A positive family history of dementia suggests a genetic cause of AD.
AD is characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins. Three genes have been discovered that cause early onset (familial) AD. Other genetic mutations that cause excessive accumulation of amyloid protein are associated with age-related (sporadic).
Although the pathophysiology of AD is not well understood, histopathologic examination of affected brain tissue clearly indicates a selective loss of cholinergic neurons. This is the rationale behind the use of anticholineesterases in the treatment of AD.
A progressive dementia that presents without sensorimotor affection in patients >70 years old. President Ronald Reagan is a famous example.
- Neat appearance, social amenities preserved until late
- Personality changes + affective shallowness
- Disoriented due to loss of spatial or event memory loss
- Language defects
- Little insight (although some patients have insight)
A Mini-mental status examination (MMSE) score < 24 (out of a total score of 30) is suggestive of dementia. If the mini-mental status examination scores normal in patients presenting with intellectual deficits a formal neuropsychological evaluation conducted by a neuropsychologist should be performed.
MRI of the brain is mainly done to exclude other causes (tumor, subdural hematoma, normal pressure hydrocephalus). Early in the disease course the MRI is normal, while later the imaging findings are not specific with generalized cortical and subcortical atrophy slightly greater than the general population. The atrophy may be more prominent in the parietal and temporal lobes of the brain. The most characteristic focal finding in AD is reduced hippocampal volume or medial temporal lobe atrophy.
Parietal hypometabolism shown on PET or parietal hypoperfusion shown on SPECT or PET support the diagnosis of Alzheimer’s disease
The management of Alzheimer’s disease is difficult and frustrating, because there is no specific treatment and no way to slow the progression of the disease. The primary focus is on long-term amelioration of associated behavioral and neurologic problems. For some people (approximately 10 to 20%) in the early or middle stages of AD, medication with anticholineesterases such as tacrine (Cognex) may alleviate some cognitive symptoms. Other anticholineesterases include donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) may keep some symptoms from becoming worse for a limited time.
A fifth drug, memantine (Namenda), was recently approved for use in the United States. Memantine blocks a is a glutamate receptor known as N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR). Combining memantine with other anticholineesterase AD drugs may be more effective than any single therapy. One controlled clinical trial found that patients receiving donepezil plus memantine had better cognition and other functions than patients receiving donepezil alone. Also, other medications may help control behavioral symptoms such as sleeplessness, agitation, wandering, anxiety, and depression.
Haloperidol is useful in relieving agitation later in the course of the disease.
AD is a progressive disease, but its course can vary from 5 to 20 years. The most common cause of death in AD patients is infection.