Review ArticleClinical Review

Managing Alzheimer Dementia Tomorrow

Thomas C. Rosenthal and Natan Khotianov
The Journal of the American Board of Family Practice September 2003, 16 (5) 423-434; DOI: https://doi.org/10.3122/jabfm.16.5.423

Article Figures & Data

Figures

  • Figure 1.
    Figure 1.

    Secretase and Alzheimer disease. Amyloid precursor proteins (APP) serve active and passive structural functions in the cell wall of neurons. To be activated, they are cleaved by α-secretase fragments that may play a role in cell adhesion. β-Secretase cleaves APP at a different site, producing a 42-amino acid fragment that can further be acted on by γ-secretase to produce β-amyloid, a protein fragment with low solubility that can aggregate and adhere to the neuron cell wall causing damage.

  • Figure 2.
    Figure 2.

    τ-Protein phosphorylation. The role of τ-protein in the cell is to provide structural support to microtubules. In the presence of kinase, τ can become phosphorylated, causing microtubules to disorganize and form tangles that disrupt intracellular transport. Phosphorylation seems to be influenced by the presence of β-amyloid.

  • Figure 3.
    Figure 3.

    Clock drawing test. The patient is asked to draw clock displaying the time 2:45. This simple test has been shown to be more sensitive of early Alzheimer dementia than several other screening tools and can be scored according to standard protocols.43

Tables

  • Table 1.

    Strategies to Slow the Onset or Progression of Dementia

    StrategyCommentsEvidence
    Maintain general healthDiet, exercise, cardiovascular risk factorsLevel B
    Intellectual achievementChallenging work.Level B
    Memory games have been shown to increase dendrites.
    Acetylcholinesterase inhibitorsInduce limited improvement in responders that can last 1 or more years.Level A
    β-Secretase inhibitionCritical enzyme in the production of β-amyloid.Basic research
    Inhibitors capable of crossing the blood-brain barrier are under development.
    ImmunotherapyAntibodies to β-amyloid increase its clearance from the brain in mice.Basic research in humans has begun.
    Vitamin E (antioxidant)Has been demonstrated to slow Alzheimer disease progression in humans but did not improve function.Level A
    Other antioxidants (ginkgo biloba, vitamin C, selegiline)Results are inconsistent, ranging from no benefit to minimal delayed progression.Inconsistent, probably not effective.
    EstrogenAlters cholinergic, serotonergic, and catecholaminergic neurotransmitter systems but increases incidence of ASHD.Inconsistent, possibly limited by side effects.
    Nonsteroidal anti-inflammatory drugs (NSAIDs)Effective only if started in the preclinical phase and used for a minimum of 2 yearsLevel B but limited by side effects. Some inconsistency in clinical trials, especially with cyclooxygenase 2 inhibitors.
    3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins)There is observational evidence that aggressive treatment of hypertension and hyperlipidemia retards onset of Alzheimer disease.Level B
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