Alzheimer's & other dementias
Another study using a different strain of genetically engineered mice has confirmed the finding that the transplant drug rapamycin prevented cognitive impairment.
A few months ago, I reported on an exciting finding that rapamycin, a drug currently used in transplant patients, improved memory in Alzheimer's mice. Now a different strain of mice (ones engineered to have defects in the genes that make amyloid precursor protein) has also shown improvements in learning and memory, correlated with less damage in brain tissue, after rapamycin treatment lowered levels of amyloid-beta-42. The mice given the drug performed at levels comparable with normal mice.
 Spilman, P., Podlutskaya N., Hart M. J., Debnath J., Gorostiza O., Bredesen D., et al.
(2010). Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease.
PLoS ONE. 5(4), e9979 - e9979.
The American Academy of Neurology has updated its guidelines on when people with dementia should stop driving. The guidelines support caregivers’ instincts, but not use of the patient’s own self-rating.
The American Academy of Neurology has updated its guidelines on when people with dementia should stop driving. While the guidelines point out that this decision is a complex one that should be made by a doctor using the Clinical Dementia Rating scale, they also supported caregivers’ instincts, which have been found to often be correct. For caregivers and family members, the following warning signs are identified:
However, the patient’s own self-rating, and a lack of situational avoidance, are not regarded as useful evidence.
 Iverson, D. J., Gronseth G. S., Reger M. A., Classen S., Dubinsky R. M., & Rizzo M.
(2010). Practice Parameter update: Evaluation and management of driving risk in dementia: Report of the Quality Standards Subcommittee of the American Academy of Neurology.
Neurology. 74(16), 1316 - 1324.
Another gene has been identified that appears to increase risk of Alzheimer’s. The gene is involved in influencing the body's levels of homocysteine (high levels are known to be a strong risk factor), and have also been implicated in coronary artery disease.
Another gene has been identified that appears to increase risk of Alzheimer’s. The gene, MTHFD1L, is located on chromosome six. Comparison of the genomes of 2,269 people with late-onset Alzheimer's disease and 3,107 people without the disease found those with a particular variation in this gene were almost twice as likely to develop Alzheimer's disease as those people without the variation. The gene is involved in influencing the body's levels of homocysteine (high levels are known to be a strong risk factor), and have also been implicated in coronary artery disease.
The results were presented at the American Academy of Neurology's 62nd Annual Meeting in Toronto, April 10–17, 2010.
The Phase II clinical trial of a treatment using naturally occurring antibodies has been successful in slowing (and in some cases preventing) the progression of the disease in patients with mild-to-moderate Alzheimer's. A much larger trial is now being carried out.
The Phase II clinical trial of a treatment using naturally occurring antibodies (IGIV) has achieved significantly lower rates of ventricular enlargement (6.7% vs 12.7% per year) and less whole-brain atrophy (1.6% vs 2.2% per year) than control subjects who initially received placebo. The trial ran for 18 months and involved 24 patients with mild to moderate Alzheimer's disease, of whom 16 received IGIV once or twice a month for the whole period, and 8 received a placebo for the first 6 months. Those who responded best to IGIV did not measurably decline over 18 months, and had an average rate of brain shrinkage and average rate of ventricular enlargement comparable to the rate previously reported in normal elderly individuals. Most tellingly, differences in rates were associated with dosage rates (there were four different regimens). A much larger trial is now being carried out.
The results were presented April 13 at the American Academy of 62nd Annual Meeting in Toronto.
Previous research has found that unexplained weight loss is an early sign of Alzheimer's. Now a new study has revealed that it is not the overall weight or fat levels that are important, but the loss of lean mass (weight of an individual's bones, muscles and organs without body fat).
Previous research has found that unexplained weight loss is an early sign of Alzheimer's. Now a study involving 140 older adults (60+), of whom half had early-stage Alzheimer's disease, has revealed that it is not the overall weight or fat levels that are important, but the loss of lean mass (weight of an individual's bones, muscles and organs without body fat). This directly correlated with reductions in the volume of the whole brain and of white matter only, along with declines in cognitive performance. The finding is consistent with research suggesting that brain pathology contributes to a decline in body composition, perhaps by disrupting the regulation of energy metabolism and food intake, perhaps through behavioral changes (there is a strong association between loss of muscle mass and reductions in physical activity), or perhaps through a common underlying mechanism, such as inflammation.
 Burns, J. M., Johnson D. K., Watts A., Swerdlow R. H., & Brooks W. M.
(2010). Reduced Lean Mass in Early Alzheimer Disease and Its Association With Brain Atrophy.
Arch Neurol. 67(4), 428 - 433.
Alzheimer's mice significantly benefited from taking a drug used to treat hypertension.
Two mouse experiments have found that the drug carvedilol, prescribed for the treatment of hypertension, significantly improved synaptic transmission in Alzheimer's disease-type brains, and at a behavioral level significantly improved learning and memory.
 Wang, J., Ono K., Dickstein D. L., Arrieta-Cruz I., Zhao W., Qian X., et al.
(Submitted). Carvedilol as a potential novel agent for the treatment of Alzheimer's disease.
Neurobiology of Aging. In Press, Corrected Proof,
Arrieta-Cruz, I. et al. 2010. Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer’s Disease. Journal of Alzheimer's Disease, 21 (2), in press.
A study finds poor learning plus depression or slow processing speed predicts the development of amnestic mild cognitive impairment for seniors.
Amnestic mild cognitive impairment often leads to Alzheimer's disease, but what predicts aMCI? A study involving 94 older adults has revealed that lower performance on tests measuring learning, in conjunction with either slower visuomotor processing speed or depressive symptoms, predicted the development of aMCI a year later with an accuracy of 80-100%. It is worth emphasizing that poor learning alone was not predictive in that time-frame, although one learning measure was predictive of aMCI two years later. Interestingly, neither gender nor possession of the ‘Alzheimer’s gene’ —long believed to be risk factors for mild cognitive impairment — had any substantial influence on later impairment.
 Han, D. S., Suzuki H., Jak A. J., Chang Y-L., Salmon D. P., & Bondi M. W.
(2010). Hierarchical Cognitive and Psychosocial Predictors of Amnestic Mild Cognitive Impairment.
Journal of the International Neuropsychological Society. 16(04), 721 - 729.
A pilot study found daily apple juice improved behavioral and psychotic symptoms in those with moderate-to-severe Alzheimer’s.
A pilot study involving 21 institutionalized individuals with moderate-to-severe Alzheimer’s found that, although drinking two 4-oz glasses of apple juice daily for a month produced no change in the Dementia Rating Scale or in the Activities of Daily Living measure, there was a significant (27%) improvement in behavioral and psychotic symptoms. The largest changes occurred in anxiety, agitation, and delusion.
 Remington, R., Chan A., Lepore A., Kotlya E., & Shea T. B.
(2010). Apple Juice Improved Behavioral But Not Cognitive Symptoms in Moderate-to-Late Stage Alzheimer’s Disease in an Open-Label Pilot Study.
American Journal of Alzheimer's Disease and Other Dementias. 367 - 371.
Full text is available free for a limited time at http://aja.sagepub.com/cgi/reprint/25/4/367.
A pilot study found two weeks of daily repetitive transcranial magnetic stimulation to the prefrontal lobes improved speech comprehension in those with moderate Alzheimer's.
A pilot study involving 10 patients with moderate Alzheimer's disease, of whom half were randomly assigned to the treatment, has found that two weeks of receiving daily (25 minute) periods of repetitive transcranial magnetic stimulation to the prefrontal lobes produced a significant improvement in the patients’ ability to understand spoken language. Correct answers on a comprehension test rose from 66% to over 77%. Two further weeks of the treatment produced no further improvement, but the improvements were still evident eight weeks after the end of the treatment. The effect was limited to this specific cognitive function.
 Cotelli, M., Calabria M., Manenti R., Rosini S., Zanetti O., Cappa S. F., et al.
(2010). Improved language performance in Alzheimer disease following brain stimulation.
Journal of Neurology, Neurosurgery & Psychiatry.
The most common type of Alzheimer's drugs (cholinesterase inhibitors) was associated with improved attention and driving skills in those with early stage Alzheimer's.
A study involving outpatients with early stage Alzheimer’s found that their performance on some computerized tests of executive function and visual attention, including a simulated driving task, improved significantly after three months of taking cholinesterase inhibitors. Specifically, the drug treatment was associated with an improved ability to accurately maintain lane position during the simulated driving task; to accurately and quickly detect a target in a visual search task; to more quickly complete computerized mazes.
 Daiello, L. A., Ott B. R., Festa E. K., Friedman M., Miller L. A., & Heindel W. C.
(2010). Effects of Cholinesterase Inhibitors on Visual Attention in Drivers With Alzheimer Disease.
Journal of Clinical Psychopharmacology. 30(3), 245 - 251.
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