Alzheimer’s Disease: The Physician’s Guide to Practical Management

The goal of this physician’s guide is to provide scientific and clinical knowledge about Alzheimer’s disease in comprehensible language. The editors have accomplished this with wonderfully succinct and short chapters. The focus of the presentations is to help practicing clinicians understand, diagnose, and treat Alzheimer’s disease, which is still underdiagnosed and undertreated.

The first section of the book covers the scientific background of Alzheimer’s disease. The first neuropathological hallmark of the disease is the presence of extracellular precipitations of beta-amyloid peptide. The second neuropathological hallmark is the presence of neurofibrillary inclusions composed of the tau protein. Lesions develop in the form of neurofibrillary tangles, first described by Aloys Alzheimer (1907), and threads. In addition to these hallmarks, Alzheimer’s disease brains also appear to exhibit evidence of reactive-oxygen-mediated injury (oxidative stress).

The epidemiology of Alzheimer’s disease indicates that 4%–10% of the population over 65 has the disease, and the percentage doubles every 5 years after age 65. In the United States, $174,000 is spent on each Alzheimer’s disease patient; with steadily increasing life expectancy, the number of patients is expected to rise from 9 million to 45 million by 2030. European studies indicate that women are at greater risk than men for developing Alzheimer’s disease after age 85; U.S. studies do not confirm this difference. There is no gender difference for rates and risks for vascular dementia. Interestingly, Native Americans appear to have a significantly lower rate of Alzheimer’s disease, although their aggregate rate of all dementias is similar to that of Caucasians. The economic burden of Alzheimer’s disease varies among countries; cost of illness studies indicate annual per patient costs of $6,500 (England), $24,400 (Sweden), $59,700 (Italy), and $53,300 (United States). Costs increase fourfold from the mild stage of Alzheimer’s disease to the severe stage.

The clinical assessment of Alzheimer’s disease is made by determining if there is an impairment of recent memory and at least one or more other cognitive disturbance: aphasia, apraxia, agnosia, and a disturbance in executive function. Folstein’s Mini-Mental State Examination (1) is a reliable and sophisticated test for assessing Alzheimer’s disease. A score of 24 out of 30 is usually indicative of Alzheimer’s disease, and a score of 20 or below will correlate to substantial impairment in activities of daily living.

Neuroimaging has the potential to go beyond its traditional role of simply ruling out mass lesions and stroke to helping diagnose specific dementing diseases. Research shows that magnetic resonance imaging (MRI) can identify early structural changes caused by Alzheimer’s disease. Furthermore, molecular neuroimaging techniques (single photon emission computed tomography [SPECT] and positron emission tomography [PET]) reveal characteristic focal abnormalities in neurodegenerative diseases that are unrecognized by other methods.

Vascular cognitive impairment (previously termed senility, multi-infarct dementia, and vascular dementia) is the second most common single cause of dementia after Alzheimer’s disease. Incidence rates are about 5% in the elderly. Clinical indicators are abrupt onset, stepwise deterioration, fluctuating course, prolonged plateaus, early gait, seizure, urinary disturbance, and a history of stroke. Cognitive deficits are patchy rather than diffuse. Vascular dementia patients have a higher mortality rate than Alzheimer’s disease patients and have a median survival of 3.31 years, as opposed to Alzheimer’s disease patients, who live an average of about 5 years and up to 20 years in rare cases. Vascular patients also typically have more medical diagnoses than Alzheimer’s disease patients.

The clinical laboratory workup for dementia varies with how well the physician knows the patient. A titer for Lyme disease may be appropriate in the Northeast. HIV testing may be needed (yes, for the elderly, too). For a patient not well-known, laboratory tests including SMAC 25 should be done. Vitamin B deficiency levels should be determined because B12 deficiency may produce significant neuropsychiatric symptoms. Elevated thyroid-stimulating hormone levels carry a greater risk for dementia.

Imaging techniques such as computerized tomography or MRI are now standard practice. Structural imaging will reveal brain atrophy, besides hematomas and tumors. Serial MRI may detect decreases in hippocampal volume. Measuring glucose metabolism with [¹⁸F]fluorodeoxyglucose PET is now recognized as a useful biological marker of dementia and for distinguishing the type of dementing neurodegenerative disease.

There are now drugs available to treat Alzheimer’s disease that do not stop the degenerative process but appear to delay it for up to 24 months. The most effective of these are the acetylcholinesterase inhibitors: donepezil, rivastigmine tartrate, and galantamine hydrobromide. Each has been shown to delay cognitive decline and improve global functioning. Galantamine hydrobromide, the most recent of these drugs, appears to be beneficial with both Alzheimer’s disease and cerebrovascular disease. The newest drug, an N-methyl-d-aspartic acid (NMDA) receptor antagonist, memantine, has demonstrated improvement in individual symptoms and clinical evidence for neuroprotection. It is believed that the NMDA drug protects the brain from glutamate-mediated neurotoxicity.

There are many interesting topics and brief chapters that contribute greatly to this book by providing much detail. Included are chapters on Lewy body disease, the transitional stage to Alzheimer’s disease, and distinguishing Alzheimer’s disease from normal aging. This is an excellent reference for the geriatric practitioner.