Recent research on Alzheimer's Disease
October 02, 2007
Medicine | Science

A quick survey of some of the more interesting research on Alzheimer's Disease recently:

I. Causes and Disease Mechanisms
Alzheimer's Disease Could Be A Third Form Of Diabetes

Science Daily Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer's memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer's disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer's removes insulin receptors from nerve cells, rendering those neurons insulin resistant. ..

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Posted by ellen at October 02, 2007 12:07 PM

...With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer's disease, the Northwestern study sheds light on the emerging idea of Alzheimer's being a "type 3" diabetes.

Useful definitions for the next few articles:

  • Oxidative stress
    is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. All forms of life maintain a reducing environment within their cells. This reducing environment is preserved by enzymes that maintain the reduced state through a constant input of metabolic energy. Disturbances in this normal redox state can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA.
    In humans, oxidative stress is involved in many diseases, such as atherosclerosis, Parkinson's disease and Alzheimer's disease and it may also be important in ageing. However, reactive oxygen species can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. Reactive oxygen species are also used in cell signaling. This is dubbed redox signaling.
    (from the Wikipedia article on Oxidative Stress)

  • Mitogenic
    Causing mitosis or transformation.
    (from the

  • Alzheimer disease, the two-hit hypothesis: an update.
    we proposed a two-hit hypothesis 2 years ago stating that both oxidative stress and mitogenic dysregulation are necessary and sufficient to cause the disease and suggested that it may be a common mechanism for other neurodegenerative diseases as well (X. Zhu, A.K. Raina, G. Perry, M.A. Smith, Alzheimer's disease: the two-hit hypothesis, Lancet Neurol. 3 (2004) 219-226). Recent developments in the field confirm some important predictions of the hypothesis and shed new lights on potential mechanisms regarding how steady state may be achieved in sporadic AD cases and therefore, in our opinion, strengthen the hypothesis, which will be the focus of this review.

    Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease.

    Besides the genetic, biochemical and neuropathological analogies between Down's syndrome (DS) and Alzheimer's disease (AD), there is ample evidence of the involvement of oxidative stress (OS) in the pathogenesis of both disorders.

    The present paper reviews the publications on DS and AD in the past 10 years in light of the "gene dosage" and "two-hit" hypotheses, with regard to the alterations caused by OS in both the central nervous system and the periphery, and the main pipeline of antioxidant therapeutic strategies. OS occurs decades prior to the signature pathology and manifests as lipid, protein and DNA oxidation, and mitochondrial abnormalities. In clinical settings, the assessment of OS has traditionally been hampered by the use of assays that suffer from inherent problems related to specificity and/or sensitivity, which explains some of the conflicting results presented in this work. For DS, no scientifically proven diet or drug is yet available, and AD trials have not provided a satisfactory approach for the prevention of and therapy against OS, although most of them still need evidence-based confirmation. In the future, a balanced up-regulation of endogenous antioxidants, together with multiple exogenous antioxidant supplementation, may be expected to be one of the most promising treatment methods.

    II. Diagnosis and Disease markers

    Linguistic changes in verbal expression: a preclinical marker of Alzheimer's disease.

    The objective of this study was to determine whether changes in verbal expression occur in the preclinical phase of AD. ...

    The sample consisted of 40 healthy Spanish speakers from Antioquia, Colombia. A total of 19 were carriers of the E280A mutation in the Presenilin 1 gene, and 21 were noncarrier family members. ...
    ...All the participants were shown the Cookie Theft Picture Card from the Boston Diagnostic Aphasia Examination and were asked to describe the scene.

    ...Carriers of the mutation produced fewer semantic categories than noncarriers. In the preclinical phase of AD, changes in verbal expression are apparent and early detection of these differences may assist the early diagnosis of and intervention in this disease.

    Cognitive decline in Alzheimer disease: Impact of spirituality, religiosity, and QOL.

    ...we recruited 70 patients with probable AD. ...The Mini-Mental State Examination was used to monitor the rate of cognitive decline. Religiosity and spirituality were measured using standardized scales that assess spirituality, religiosity, and organizational and private religious practices. ...

    After controlling for baseline level of cognition, age, sex, and education, a slower rate of cognitive decline was associated with higher levels of spirituality (p < 0.05) and private religious practices (p < 0.005).
    ...There was no correlation between rate of cognitive decline and QOL. CONCLUSION: Higher levels of spirituality and private religious practices, but not quality of life, are associated with slower progression of Alzheimer disease.

    September 11, 2001, and flashbulb memory in Alzheimer's disease: tool for assessing memory problems in daily practice

    Public events memory" is a semantic memory that may have episodic components. One aspect involves what is called flashbulb memory, in which individuals retain vivid and detailed recollection of circumstances in which they learned of an event.

    The study examined questioned 30 subjects with AD and 36 control subjects about their memory of the terrorist attacks that day. RESULTS: Subjects with AD, even those in early disease, appeared to have less detailed recollections of the event, in terms of evocation, dating, and responses to questions. They also had flashbulb memories associated with it less often than controls (46% of cases compared with 97.3% of the control subjects). DISCUSSION: The excellent performance of control subjects underlines the memory impairment about this event in patients with AD. Questions about this topic may be a good tool for general practitioners assessing the need for further evaluation in patients with memory complaints.

    Conscientiousness and the Incidence of Alzheimer Disease and Mild Cognitive Impairment

    By Judith Groch, Senior Writer, MedPage Today

    A neat orderly mind augmented by a conscientious personality tends to resist Alzheimer's disease, researchers here found.

    Self-disciplined and goal-directed persons who scored high on a standard measure of conscientiousness had an 89% lower risk of developing Alzheimer's than those with low scores, Robert S. Wilson, Ph.D., of Rush University, and colleagues, reported in the October issue of the Archives of General Psychiatry.

    Epidemiologic research has shown that conscientiousness is associated with a wide range of mental and physical disorders, disability, and death, suggesting that the trait has some general role in health maintenance, the researchers said....

    ...Because mild cognitive impairment is increasingly viewed as a state that precedes clinically evident dementia in Alzheimer's, the researchers conducted a further analysis. They found that a higher level of conscientiousness was associated with a reduced risk of mild cognitive impairment (HR, 0.977, 95% CI, 0.956-0.999).

    ...There are several ways conscientiousness might protect against Alzheimer's disease, the researchers said. Controlling for cardiovascular health and lifestyle activity patterns did not substantially affect the findings, they found.

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