alzheimers write up discussion

Alzheimer’s dementia is an irreversible and progressive degenerative neurologic disorder that is insidious in onset and ultimately fatal. Alzheimer’s is most commonly associated with old age, and it is estimated that between 20-40% of those older than 85 have some form of this disease. I would like to briefly review the clinical presentation, pathology, and current efforts at treatment for this tragic disease.

Alzheimer’s first manifests through declarative memory impairment; patients will typically have word finding difficulties as well as problems naming common objects or names. Long-term memories from decades past are preserved (wedding dates, names of children) and a profound anterograde amnesia takes hold. However, motor task skills and basic social skills are normally preserved during this period, as are language and visuospatial skills. Patients are often disoriented, and although they are capable of spontaneous speech they can be wildly tangential. As the dementia progresses language skills inevitably regress. 10% of patients can demonstrate a phenomenon termed Capgras syndrome a delusional disorder characterized by the belief that their caretaker has been replaced by an imposter. Another characteristic of Alzheimer’s dementia is anosognosia, the patient lacks insight into their own dementia. As a result of this the patient’s may confabulate details or simply display a pleasant disorientation. Patients may wander, especially at night, and may become lost. Patients’ may also display a masked expressionless face, normally characteristic of Parkinsonism. Unfortunately as the disease progresses the dementia strips the patient of basic functioning and they can become rigid, bed bound, incontinent, and agitated. Death normally results from malnutrition, infection, or pulmonary embolus. The average time from onset of symptoms to death is between 8 to 10 years, however it can be as soon as 1 year and as long as 25 years.

The characteristic post mortem pathologies of Alzheimer’s patients are extracellular neuritic plaques and intracellular neurofibrillary tangles. The plaques are composed of aggregates of a transmembrane protein beta-amyloid. The intracellular neurofibrillary tangles are composed of twists of mictrotubules and their associated stabilizing protein Tau (except in this case the Tau is abnormally hyperphosphorylated, a state believed to contribute to its pathological effect). The current belief is that as these proteins accumulate they interfere with normal cellular functioning and eventually become toxic. On autopsy, brains of Alzheimer’s patients have greater plaque and tangle burdens in the hippocampus, tempo-parietal cortex and nucleus basalis of Meynert; neuroanatomical locations that accurately reflect the deficits during life.

Unfortunately there are no treatments that can improve, reverse, or halt the course the disease. Current treatments available for patients diagnosed with Alzheimer’s are primarily symptomatic. Acetylcholinesterase inhibtors such as donepezil, rivastigmine, and galantamine exert their effect by improving neurotransmission in the nucleus basailis of Meynert but their efficacy is limited. Memantine, an NMDA receptor antagonist blocks pathological glutamate excitotoxicity in hippocampal neurons and has been shown to have a small but significant effect in improving cognition, however side effects such as hallucination and agitation have been described. Finally, the well-known anti-oxidant Vitamin E (alpha tocopherol) has been shown to have a modest but measurable effect in delaying clinical endpoits in trials, and has been recommened as a treatment for those patients without heart disease.