Alzheimers Disease
Copyright 2010
Definition
Alzheimer?s is a degenerative disorder of the brain that is most commonly caused by the aging process and is one of the commonest diseases of the elderly. It results in progressive loss of brain function.
Structurally it is characterized by the presence of neuritic plaques of amyloid that surrounds blood vessels, and neurofibrillary tangles in the neuronal cytoplasm. Functionally it is characterized by short term memory loss and behavioral symptoms.
Clinically the patients present with language disorders and impairment in their visuospatial skills and executive functions. Psychiatric changes are also noted, with changes in behavior, accompanied by depression, insomnia, delusions and hallucinations (mostly secondary to the loss of memory).
The diagnosis is made by MRI identifying cortical and hippocampal atrophy associated with prominent atrophy in the temporal and parietal lobes and, later in the course, in the frontal lobe are the typical findings that go along the usual course.
No effective treatment is known to date. Most of the current therapies can only mildly address the symptoms, through modulation of neurotransmitters – either acetylcholine or glutamate, because some of the symptoms are due to loss of cholinergic innervation to the cerebral cortex.
Background
The disorder was described in 1907 by the German psychiatrist and neuropathologist Alois Alzheimer.
In 1901, Alzheimer observed a patient named Mrs. Auguste Deter, who had strange behavioral symptoms, and short-term memory loss. Alzheimer had the patient records and the brain from autopsy later was sent to Munich where, with Dr. Kraepelin, he used staining techniques that revealed neuritic plaques clustered around a central amyloid core, along with generalized brain atrophy.
The disease, which was considered rare and confined to the persons younger than 65 years of age, had been described in the mid-20th century in not more than 100 people. Alzheimer’s has presently become one of the most common diseases of the elderly.
Cause
In Alzheimer’s, as described below, there is a progressive loss of brain functions which are explained by the presence of neuritic plaques seen microscopically containing Ab amyloid, silver-staining neurofibrillary tangles in neuronal cytoplasm, and accumulation of Ab42 amyloid in arterial walls of cerebral blood vessels.
Alzheimer’s prevalence increases dramatically after the age of 65, doubling every 5-year age group. The are around 3 new cases yearly per 100,000 persons younger than age 60 years, and 125 new cases per 100,000 of people older age 60 years. Besides age, risk factors are lower education level, family history, coronary artery disease, and carrying the apoE4 allele.
The disease usually appears late in life, but if occurring earlier, than an autosomal dominant inheritance can be involved.
The disease seems to be more prevalent in women rather than men. As the aging population is increasing radically by the next 50 years, Alzheimer’s will be an ever-increasing public health problem in the decades to come.
Resulting in
A progressive loss of brain functions that start with deterioration of recent episodic memory.
Presentation
Patients may gradually develop language disorders and impairment in their visuospatial skills and executive functions. Psychiatric changes are also noted, with changes in behavior, accompanied by depression, insomnia, delusions and hallucinations (mostly secondary to the loss of memory). Actually, up to 20% of patients present initially with organizational complaints or navigational difficulty rather than loss of memory, though a clue may be a problem finding words. Some patients are unaware of their losses, while others have considerable insight of the situation
Diagnosis
Radiologic imaging has aided the accurate diagnosis of Alzheimer’s. The most striking feature is a generalized cerebral atrophy, that may not be present in early stages of the disease however. Cortical and hippocampal atrophy associated with prominent atrophy in the temporal and parietal lobes and, later in the course, in the frontal lobe are the typical findings that go along the usual course. Also, it can provide and increase accuracy in diagnosis by ruling out other pathologies that enter in the differential diagnoses, mostly structural lesions such as tumors, hydrocephalus, subdural hemorrhage. Vascular dementia is also properly evaluated through MRI.
Treatment
No effective treatment is known to date. Most of the current therapies can only mildly address the symptoms, through modulation of neurotransmitters – either acetylcholine or glutamate, because some of the symptoms are due to loss of cholinergic innervation to the cerebral cortex.
Alzheimer’s Disease beta-amyloid plaques and neurofibrillary tangles cause dementia in patients over 60, ApoE4 is a high risk allele