treatment

Montessori for Alzheimer's patients

Cameron Camp, director of the Myers Research Institute, began looking at the Montessori method as a way of helping Alzheimer's patients some 10 years ago. The Montessori method, developed for young children, is rooted in the senses, and involves manipulating everyday objects and following highly structured activities that engage children but rarely allow them to fail. Camp adapted these activities for Alzheimer's patients, tailoring them to the individual's background and interests. You can read about the program and its success in improving the quality of life for Alzheimer's patients and their caregivers in a number of online articles:

http://www.aarp.org/bulletin/longterm/Articles/alzheimer.html

http://www.providermagazine.com/pdf/cover-12-2005.pdf (pdf document)

http://www.nursinghomesmagazine.com/Past_Issues.htm?ID=3815

http://www.vcu.edu/vcoa/ageaction/AGEfa03.htm

Below are several manuals co-written by Cameron Camp. You can also read about these books at the Myers Research Institute site at http://www.myersresearch.org/manuals.html and listen to radio interviews given by Dr Camp at http://www.myersresearch.org/media.html

A Montessori Program is also now used at Truman Medical Center Lakewood for its Alzheimer residents. The program focuses on Montessori activities that will help each resident continue to be independent as long as possible. You can read about it here: http://www.trumed.org/sections/content.aspx?id=217&SID=92

Vascular & Mixed Dementia

Prevalence

Vascular dementia, as its name suggests, is caused by poor blood flow, produced by a single, localized stroke, or series of strokes.

It is the second most common dementia, accounting for perhaps 17% of dementias. It also co-occurs with Alzheimer's in 25-45% of cases. Although there are other types of dementia that also co-occur with Alzheimer's, mixed dementia generally refers to the co-occurrence of Alzheimer's and vascular dementia.

Risk factors

In general, unsurprisingly, vascular dementia has the same risk factors as cerebrovascular disease.

A study1 of 173 people from the Scottish Mental Survey of 1932 who have developed dementia has found that, compared to matched controls, those with vascular dementia were 40% more likely to have low IQ scores when they were children than the people who did not develop dementia. Because this was not true for those with Alzheimer's disease, it suggests that low childhood IQ may act as a risk factor for vascular dementia through vascular risks rather than the "cognitive reserve" theory.

Prevention

The exciting thing about vascular dementia is that it is far more preventable than other forms of dementia. As with risk, as a general rule, the same things that help you protect you from heart attacks and stroke will help protect you from vascular dementia. This means diet, and it means exercise.

A four-year study2 involving 749 older adults has found that the top one-third of participants who exerted the most energy in moderate activities such as walking were significantly less likely to develop vascular dementia than those people in the bottom one-third of the group.

Treatment

Apart from normal medical treatment for cerebrovascular problems, there are a couple of interesting Chinese studies that have looked specifically at vascular dementia.

The herb gastrodine has been used in China for centuries to treat disorders such as dizziness, headache and even ischemic stroke. A 12-week, randomized, double-blind trial3 involving 120 stroke patients who were diagnosed with mild to moderate vascular dementia has found that  gastrodine and Duxil® (a drug used to treat stroke patients in China) produced similar overall levels of cognitive improvement -- although more patients showed 'much improvement' with gastrodine (23% vs 14%).

A Chinese pilot study4 involving 25 patients with mild to moderate vascular dementia found that ginseng compound significantly improved their average memory function after 12 weeks, but more research (larger samples, placebo-controls) is needed before this finding can be confirmed. Five years on I have still not seen such a study.

References: 
  1. McGurn, B., Deary, I.J. & Starr, J.M. 2008. Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia. Neurology, first published on June 25, 2008 as doi: doi:10.1212/01.wnl.0000319692.20283.10
  2. Ravaglia, G. et al. 2007. Physical activity and dementia risk in the elderly. Findings from a prospective Italian study. Neurology, published online ahead of print December 19.
  3. Tian, J.Z. et al. 2003. A double-blind, randomized controlled clinical trial of compound of Gastrodine in treatment of mild and moderate vascular dementia in Beijing, China. Presented at the American Heart Association's Second Asia Pacific Scientific Forum in Honolulu on June 10.
  4. Tian, J.Z. et al. 2003. Presented at the American Stroke Association's 28th International Stroke Conference on February 14 in Phoenix. Press release

Movement with Meaning

Barbara Larsen is the creator of a program called "Movement with Meaning", that aims to help Alzheimer's sufferers "hold onto" themselves for as long as possible. She's also written a book about the program: Movement With Meaning: A Multisensory Program for Individuals With Early-stage Alzheimer's Disease. And she's kindly written an article about the program just for us. Here it is.

Movement with Meaning: A Multisensory Program for Individuals in Early-Stage Alzheimer's Disease

Those of us in the field of dementia care are reexamining our philosophical beliefs and exploring practical, hands-on approaches in our relationships with individuals living with Alzheimer's disease. We are creating innovative programs and developing a new framework for preserving the emotional health, autonomy, and dignity of those who need us to walk hand in hand with them, witnessing the process of their experiences with empathy and respect.

Movement with Meaning is one such program. Designed for persons in the early stage of Alzheimer's disease, Movement with Meaning reinforces the remaining strengths and abilities of people with dementia by using a multisensory approach that stimulates all five senses. Practical and interactive by nature, the curriculum is ideal for physical therapists, recreational instructors, and activity directors in adult day centers and assisted living facilities, as well as health care professionals who are senior trainers, music or dance therapists.

As the mind begins to slowly unravel, the body becomes the refuge - the container - the ground - the point of reference. In a Movement with Meaning class, the multisensory activities are divided into five segments that create a choreography of movements in which short, repetitive exercises increase a sense of well being. The program introduces simple breathing techniques, poetry, music, movement exercises (bilateral integration exercises and yoga postures), and sensory activities. Once the person with Alzheimer's disease experiences a sense of his or her inner landscape, anxiety and confusion begin to subside. Movement with Meaning provides an opportunity for the participants to recognize the abilities and talents lying dormant behind the disease and find a new path to connect and communicate with each other and their families.

What an opportunity we have with the advent of early diagnosis. So why wait? Because the long-term memory is not affected in the early stage of Alzheimer's disease, these memories are preserved. I have found that repetition is an effective method for not only retrieving these memories, but as an essential tool in a Movement with Meaning class.

A study published in the American Journal of Alzheimer's Disease and other Dementias (Jan-Feb, 2004 issue) shed light on the effectiveness of repetitive work on maintaining functional levels in Alzheimer's disease patients. In the Adapted Work Program participants were given jobs that included packaging, shredding, folding laundry, stamping and sending our mailings. The program was closed due to budget cuts in funding. The participants were transferred to a traditional day care program which included activities such as bingo, ceramics, music, and current events. Before moving to the traditional day care setting the participants were assessed with the MMSE (Mini-Mental Status Exam), the Cognitive Performance Test, and the Geriatric Depression Scale. And then reassessed again in 4 months, after being at the traditional day care facility. The MMSE and the Cognitive Performance Test scores were lower than expected. All the spouses of the participants reported declines in Activities of Daily Living. The conclusion of the study stated that activities that involve repetitive, sequencing skills promote better self-care at home than traditional day care environments. As mentioned above Movement with Meaning is divided into five segments, with a thematic thread that reinforces the continuity of the program.

The first segment in a Movement with Meaning class is "Centering through Breathing." When an individual with Alzheimer's disease experiences disorientation, has difficulty remembering names, or finding the right word, this can be unsettling and cause anxiety. The antidote to help diminish anxiety is mindful breathing. Once the mind is calm and relaxed concentration will follow. In his book, "Your Memory: How it Works, and How to Improve it," K. Higbee documents that high anxiety interferes with attention and concentration. Therefore, it is imperative to establish an environment that promotes a peaceful inner state. When participants feel relax and calm the ability retrieve firmly rooted songs, prayer, and poems begin to surface.

The second segment in a Movement with Meaning class is "Learning by Heart." The participants memorize a short poem or song. Poems and songs that were learned early in life are stored in the long-term memory and remain accessible to the person with early-stage Alzheimer's disease. Repetition is the method for learning a new poem or song. The rhythm patterns and cadence in each poem or song creates an atmosphere that is safe and nonthreatening and brings something to the lives of the participants that is representative of what was there before the disease. Included in the second segment is the use of visualization techniques to expand on the imagines evoked by a poem or song. Visualization increases concentration because it creates focus on the more subtle "mental pictures" and "feelings" of a poem or song.

The third segment is a Movement with Meaning class (A Delicate Balance and Nice and Easy Yoga) including both bilateral integration exercises and yoga postures. Problems with balance and coordination begin to occur in early-stage Alzheimer's disease. Muscles love rhythmic movement. By satiating the body with repetitive bilateral exercises or yoga postures, participants are not only integrating both left and right hemisphere of the brain but are also increasing their spatial awareness, balance, and coordination. These exercises and postures are similar to Tai Chi in that they help the participant identify the body's midline - the median plan where the left and right sides of the brain and body cross or overlap.

In a study in the Winter 2003-2004 issue of Generations an article titled: "Balance Intervention to Prevent Falls," addresses the importance of exercises that include flexibility, balance, and sensory awareness. A multidimensional program is important for fall reduction. By aligning the body with the earth, a nonverbal statement is made: "I know where my body is in time and space." By incorporating a physical component in a Movement with Meaning class, the transition from the cadence of a poem or the melody of a song is experienced as part of a continuum, unfolding a choreography of movements with a theme and purpose.

The fourth segment is a Movement with Meaning class, "A Sense of Timing," which introduces music and rhythmic exercises to help the participants integrate and embody a poem or song. The rhythm patterns are synchronized with the cadence and melody of the poem or song. Rhythmic instruments such as chimes, drums, bells, and claves are nonverbal ways of communicating. The repetition of a beat or dance evolves an inner musical sense, and inner timing. Without thinking, the participants begin to tap their feet or sway their bodies from side to side. Studies in Germany reveal that when individuals with Alzheimer's disease participate in music therapy that include rhythm instruments sensory and motor integration are promoted.

The last segment is a Movement with Meaning class, "Reawakening the Senses," devoted to using the senses of smell, taste, and touch, with attention to color, shape, and texture. Exploring the senses allows individuals with Alzheimer's disease to gain access to their own unique internal landscape. We make sense of the world through our senses. The body is the primary receptor and container of experience. Appropriate sensory stimulation is a main avenue to awakening latent memories, as well as supporting existing functional abilities.

When the elements Movement with Meaning are put together in a daily program, attention is refocused back to the body of the person with Alzheimer's disease. For whatever was lost in the cognitive realm can be recalled through the senses. As one participant in a Movement with Meaning stated when asked what she thought about the program, "I have enough to hold on to."

I'll ask the same question again: So why wait? The time is now, in the early stage, to reinforce remaining strengths and abilities. The time is now, while the individual is aware of his or her personal biography, to investigate the sense of the individual's inner landscape is changing. The time is now to create an environment that strives to preserve the identity and dignity of each individual affected by Alzheimer's disease.

Barbara Larsen, M.A., Ed.
Creator & Author, Movement with Meaning
P. O. Box 2636
Nevada City, CA 95959
blarsen@nccn.net

Unmet needs among those living at home with dementia

A study involving 254 people with dementia living at home has found that 99% of people with dementia and 97% of their caregivers had one or more unmet needs, 90% of which were safety-related. More than half of the patients had inadequate meaningful daily activities at a senior center or at home, one-third still needed a dementia evaluation or diagnosis, and more than 60% needed medical care for conditions related or unrelated to their dementia.

Prion proteins might help reduce amyloid-beta plaques

Grape skin extract may help treat diabetes

Preliminary studies have demonstrated that grape skin extract exerts a novel inhibitory activity on hyperglycemia and could be developed to aid in diabetes management.

http://www.eurekalert.org/pub_releases/2014-05/wsu--gse050814.php

Shift away from glycemic control in diabetes treatment

It is now realized that the focus in treating diabetes shouldn’t be so much on controlling blood sugar. New medical guidelines point to the importance of the following interventions (in order of benefit):

  1. smoking cessation (most important)
  2. blood pressure control
  3. metformin drug therapy
  4. lipid reduction
  5. glycemic control (least important).

This isn’t to say that blood sugar isn’t important; but the others should be dealt with first.

Cancer drug not fully confirmed for Alzheimer's treatment

Last year, a cancer drug, Bexarotene, was touted as a potential treatment for Alzheimer’s disease. However, four independent studies have now failed to replicate the most dramatic result of the original study: a claim that the drug could clear half the amyloid plaques

Alzheimer's drugs improve perception

photo of eagle

Most of the (few) approved Alzheimer’s drugs are cholinesterase inhibitors

Alzheimer's: Treatment - Neurological & surgical interventions


Older news items (pre-2010) brought over from the old website

Gene Therapy

Targeting a key enzyme with gene therapy reversed course of Alzheimer's disease in mouse models

A study using genetically engineered mice has reversed the rats' memory loss by silencing a gene that helps produce amyloid plaques. The size and number of plaques were reduced by two-thirds within a month.

Singer, O. et al. 2005. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nature Neuroscience, 8, 1343-1349.

http://www.eurekalert.org/pub_releases/2005-09/si-tak092005.php

Gene therapy slows cognitive decline in trial

The first human clinical trial of gene therapy for Alzheimer’s, involving 8 volunteers, has found an increase in the brain’s use of glucose — a sign of brain activity — and a significant slowing of the patients’ rate of cognitive decline in the 6 patients who completed the procedure safely.

Tuszynski, M.H. et al. 2005. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nature Medicine, 11(5), 551-555.

http://www.eurekalert.org/pub_releases/2005-04/uoc--acd041805.php

New gene therapy technique

A new technique using gene therapy to deliver nerve growth factor into regions of the brain where neurons are degenerating is being trialed in a two-year study. The technique, which requires neurosurgery to inject the drug precisely where it is required (the basal forebrain), uses a new drug called CERE-110. Extensive studies in several animal models, including primates, have showed that NGF gene delivery to the basal forebrain prevented the death of cholinergic neurons (which undergo severe degeneration and death in Alzheimer's disease patients).

http://www.eurekalert.org/pub_releases/2004-09/rpsl-seg092004.php

Preliminary results promising in Alzheimer's gene therapy trial

A small, preliminary study has had some success in delaying brain cell loss in early Alzheimer’s patients through the surgical placement of genetically modified tissue directly into their brains.

The study was reported on April 27 at the American Academy of Neurology meeting in San Francisco.

http://www.eurekalert.org/pub_releases/2004-04/uoc--pra042204.php

UCSD team performs first surgery in gene therapy protocol for Alzheimer's disease

In a groundbreaking procedure, physicians at the University of California, San Diego (UCSD) School of Medicine have surgically implanted genetically modified tissue into the brain of an Alzheimer's patient. This launches the first phase of an experimental gene therapy protocol for Alzheimer's disease. The therapy delivers a natural molecule called nerve growth factor (NGF) to the dying cells in the brain.
If the protocol is successful, implanted cells could begin to affect brain function in a month or two, but Tuszynski cautions that "it may take several years to test the procedure in a large enough number of patients to determine whether it will be useful therapy." The therapy is not expected to cure Alzheimer's disease, but it may restore some brain cells and alleviate symptoms such as short-term memory loss for several years.

Conner, J. M., Darracq, M. A., Roberts, J., & Tuszynski, M. H. (2001). Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation. Proceedings of the National Academy of Sciences, 98(4), 1941–1946. doi:10.1073/pnas.98.4.1941

http://www.eurekalert.org/pub_releases/2001-04/UNKN-Utpf-0904101.php

CSF shunt

Draining toxins from cerebrospinal fluid stabilizes cognitive decline

The ever-slowing capacity to clear the build-up of such toxins as isoprostanes and misfolded proteins that accumulate in the brains of Alzheimer's disease patients causes the death of cells involved in memory and language. A preliminary study has shown that reducing the levels of isoprostanes by draining cerebral spinal fluid can stave off future reductions in cognitive abilities. Cognitive scores in the 8 patients receiving the treatment were stable after one year, while scores in those not receiving the treatment declined 20%. The next phase of the study involves nearly 100 patients.

Praticò, D., Yao, Y., Rokach, J., Mayo, M., Silverberg, G.G. & McGuire, D. 2004. Reduction of brain lipid peroxidation by CSF drainage in Alzheimer’s disease patients. Journal of Alzheimer's Disease, 6(4), 385-389.

http://www.eurekalert.org/pub_releases/2004-08/uopm-dti082004.php

Can Alzheimer's disease be slowed by shunting cerebrospinal fluid?

A pilot study has tested the hypothesis that improving cerebrospinal fluid (CSF) turnover will slow or stop the progression of dementia in people with Alzheimer's disease. CSF shunting for dementia, described in 1969, was largely abandoned due to mixed clinical results and an unacceptably high incidence of adverse events. However recent clinical studies in which CSF shunting was used to treat patients with symptomatic hydrocephalus demonstrated a coincidental lack of cognitive decline in patients who also had Alzheimer's dementia. A pilot study has found Alzheimer's patients who were shunted experienced relative stability while the control group demonstrated a fairly robust decline in cognitive function over the 12 months of the study. A larger, multi-center, controlled clinical trial is now underway.

Silverberg, G.D., Levinthal, E., Sullivan, E.V., Bloch, D.A., Chang, S.D., Leverenz, J., Flitman, S., Winn, R., Marciano, F., Saul, T., Huhn, S., Mayo, M. & McGuire, D. 2002. Assessment of low-flow CSF drainage as a treatment for AD: Results of a randomized pilot study. Neurology, 59, 1139-1145.

http://www.eurekalert.org/pub_releases/2002-10/aaon-cad101502.php

Possible new surgical treatment

An 18-month, double-blind placebo study into a new surgical treatment for Alzheimer’s disease using a device called the COGNIShunt, is being undertaken by neurologists at Emory University. The shunt is designed to drain cerebrospinal fluid (CSF) from the skull and into the abdominal cavity. By reducing the build-up of CSF around the brain, doctors hope this device will help to stabilize the disease. In a pilot study of the COGNIShunt, the device was well tolerated by individuals with mild to moderate Alzheimer’s disease.

http://www.eurekalert.org/pub_releases/2002-03/euhs-esc032102.php

Animal studies

Neurogenesis improved in Alzheimer mice

Studies of adult neurogenesis in genetically engineered mice have revealed two main reasons why amyloid-beta peptides and apolipoprotein E4 impair neurogenesis, and identified drug treatments that can fix it. The findings point to a deficit in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission as an important contributor to impaired neurogenesis in Alzheimer’s. While stem cell therapy for Alzheimer’s is still a long way off, these findings are a big step toward that goal.

Gang Li et al. 2009. GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice. Cell Stem Cell, 5 (6), 634-645. Binggui Sun et al. 2009. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell, 5 (6), 624-633.

http://www.eurekalert.org/pub_releases/2009-12/gi-gsi113009.php

Neural stem cells offer potential treatment for Alzheimer's

Genetically engineered mice performed markedly better on memory tests a month after neural stem cells were injected into their Alzheimer-like brains. The stem cells secreted a protein that created more neural connections, improving cognitive function. Surprisingly, only 6% of the stem cells became neurons (most became ‘support cells’: astrocytes and oligodendrocytes). The benefit of stem cells seemed rather to lie in their secretion of BDNF, which encouraged the formation of new synapses. The direct injection of BDNF also had cognitive benefit, but not as much as with the neural stem cells, which provided a more long-term and consistent supply of the protein.

Norton, M.C. et al. 2009. Caregiver–Recipient Closeness and Symptom Progression in Alzheimer Disease. The Cache County Dementia Progression Study. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, Advance Access published on June 29, 2009. Full text available at http://www.pnas.org/content/106/32/13594.abstract 

http://www.eurekalert.org/pub_releases/2009-07/uoc--nsc072009.php

Growth factor protects key brain cells in Alzheimer's models

In a series of cell culture and animal studies, involving genetically engineered mice, rats, and rhesus monkeys, injections of brain-derived neurotrophic factor (BDNF) resulted in significant improvement in brain functioning and on learning and memory tests. The growth factor, important for neurogenesis, is normally produced in the entorhinal cortex, an area damaged early in Alzheimer’s disease.

Nagahara, A.H. et al. 2009. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nature Medicine, 15, 331–337.

http://www.eurekalert.org/pub_releases/2009-02/uoc--gfp020309.php

Inhibitor of amyloid-beta clearing enzyme found

A new way of destroying amyloid-beta proteins has been found. Following previous research showing that the enzyme cathepsin B destroys the protein, scientists have now succeeded in increasing the activity of the enzyme by reducing the activity of the protease inhibitors cystatin C, the enzyme’s natural inhibitor. In mice, this had the effect of improving memory and extending life.

Sun, B. et al. 2008. Cystatin C-Cathepsin B Axis Regulates Amyloid Beta Levels and Associated Neuronal Deficits in an Animal Model of Alzheimer's Disease. Neuron, 60 (2), 247-257.

http://www.eurekalert.org/pub_releases/2008-10/gi-gsf102008.php

New way to target Alzheimer's disease

In a series of studies in transgenic mice, a synthetic peptide designed to block the interaction between apolipoprotein E and amyloid-beta protein reduced the aggregation of toxic amyloid protein in the brain by around 50%. The treated mice showed no memory decline.

Sadowski, M.J. et al. 2006. Blocking the apolipoprotein E/amyloid- interaction as a potential therapeutic approach for Alzheimer's disease. Proceedings of the National Academy of Sciences, 103, 18787-18792. The full text is available at http://www.pnas.org/cgi/content/full/103/49/18787

http://www.eurekalert.org/pub_releases/2006-12/nyum-sda120406.php

Androgen therapy may slow progress of Alzheimer's disease

Recent studies have suggested a link between testosterone loss in men and Alzheimer’s. A new study has now found a correlation between low testosterone and elevated beta-amyloid, providing more support that testosterone depletion in aging men increases the risk of Alzheimer’s. Testosterone belongs to a group of steroid hormones called androgens. The mouse study found that androgen therapy was successful in preventing beta-amyloid accumulation and cognitive decline in castrated mice.

Rosario, E.R. et al. 2006. Androgens Regulate the Development of Neuropathology in a Triple Transgenic Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 26, 13384-13389.

http://www.eurekalert.org/pub_releases/2006-12/sfn-tm121906.php

Insulin receptor stops progression of Alzheimer's

Following previous research suggesting Alzheimer's might be a brain-specific neuroendocrine disorder, or a Type 3 diabetes, a new study has found that stimulation of a receptor in the brain that controls insulin responses prevents several components of neurodegeneration and preserves learning and memory in rats with induced Alzheimer's disease, raising the possibility that patients in the very early stages of Alzheimer’s might be treatable.

de la Monte, S.M. et al. 2006. Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. Journal of Alzheimer's Disease, 10 (1), 89-109.

http://www.eurekalert.org/pub_releases/2006-09/l-irs092106.php

Brain enzyme treatment for Alzheimer's

In a new approach to treating Alzheimer’s, increasing brain levels of ubiquitin C-terminal hydrolase L1 (Uch-L1) — an enzyme that helps neurons rid themselves of excess or aberrant proteins — has restored a great deal of brain activity to mice with Alzheimer's symptoms. The enzyme Uch-L1 is part of a network that controls a memory molecule called CREB, which is inhibited by amyloid beta proteins in people with Alzheimer's. Uch-L1 is found at reduced levels in the Alzheimer's brain. As well as improving memory in genetically engineered mice, treatments that restored Uch-L1 levels corrected deficits in nerve transmission both in brain slices treated with amyloid-beta and in slices taken from transgenic mice.

Gong, B. et al. 2006. Ubiquitin Hydrolase Uch-L1 Rescues B-Amyloid-Induced Decreases in Synaptic Function and Contextual Memory. Cell, 126, 775–788.

http://www.eurekalert.org/pub_releases/2006-08/cp-bet082106.php
http://www.eurekalert.org/pub_releases/2006-08/cumc-crr082206.php

Why chances of Alzheimer's increase with age

Experiments with roundworms have revealed two important proteins that help slow down the accumulation of amyloid-beta. HSF-1 breaks apart amyloid and disposes of it — but aging slows HSF-1, so it can't keep up. DAF-16 helps it out, by clumping extra amyloid together in a way that makes it less toxic. The finding supports recent research indicating amyloid clumps, or plaques, are not the main problem, rather, smaller amyloid tendrils inside cells are. The study also explains why aging increases the likelihood of Alzheimer’s. Most importantly of all, it suggests a new approach to treating Alzheimer’s.

Cohen, E. et al. 2006. Opposing Activities Protect Against Age-Onset Proteotoxicity. Science, 313 (5793), 1604–1610.

http://www.msnbc.msn.com/id/14290153/
http://www.boston.com/news/nation/articles/2006/08/11/scientists_find_natural_alzheimers_controls/

Potential new treatment strategy for Alzheimer's

A study has identified several new compounds that could play a role in preventing or treating Alzheimer's disease and other degenerative conditions of the nervous system. In culture, these compounds bind with a receptor called p75NTR; a receptor that in the body binds neurotrophins. There is some evidence that in Alzheimer's, some of the neurons that die express the p75NTR binding site, indicating they may be dying because neurotrophins are binding to them. Because the new compounds bind with p75NTR in place of neurotrophins, they may provide a means of preventing damage that neurotrophins would otherwise be causing. The compounds were also found to inhibit the death of oligodendrocytes.

Massa, S.M. et al. 2006. Small, Nonpeptide p75NTR Ligands Induce Survival Signaling and Inhibit proNGF-Induced Death. Journal of Neuroscience, 26, 5288-5300.

http://www.eurekalert.org/pub_releases/2006-05/uoc--pnt051706.php

Memory loss in genetically engineered mice reversed

Mice were genetically engineered to develop dementia; the transgene was designed to be able to be turned off. The researchers expected that when the transgene expressing the dementia was turned off, memory loss would stop. Instead, they were surprised to find the loss was reversed; the mice regained their memory. A further surprise occurred when it was found that the neurofibrillary tangles, thought to be one of the causes of dementia, remained, and even increased, suggesting that the tangles are not a cause of dementia.

SantaCruz, K. et al. 2005. Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function, Science, 309 (5733), 476-481.

http://www.eurekalert.org/pub_releases/2005-07/uom-uom071105.php

Inhibiting Apolipoprotein E possible means of therapeutic intervention

It has been known that the inflammatory protein ApoE can speed the buildup in the brain of amyloid plaques,but the mechanism has not been known. A mouse study found ApoE is responsible for converting harmless amyloid-beta into the toxic fibrous deposits known as filamentous amyloid. This process is needed to damage nerve cells in parts of the brain controlling memory and cognition. Mice with Alzheimer's disease showed memory deficits only when the ApoE gene was present. The study suggests that preventing ApoE from acting upon amyloid-beta may prove to be an effective means of therapeutic intervention.

Costa, D.A., Nilsson, L.N.G., Bales, K.R., Paul, S.M. & Potter, H. 2004. Apolipoprotein E is required for the formation of filamentous amyloid but not for amorphous AB deposition, in an Aâ PP/PS double transgenic mouse model of Alzheimer's disease. Journal of Alzheimer's Disease, 6, 509–514.

Nilsson, L.N.G., Arendash, G.W., Leighty, R.E., Costa, D.A., Garcia, M.F., Cracciola, J.R., Rojiani, A., Wu, X., Bales, K.R., Paul, S.M. & Potter, H. 2004. Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid. Neurobiology of Aging, 25 (9), 1153-1167.

http://www.eurekalert.org/pub_releases/2004-10/uosf-rur102904.php

Researchers identify brain protein that halts progression of Alzheimer's

Researchers have identified a protein in the brain, "transthyretin," that halts the progression of Alzheimer's disease in human brain tissue by blocking beta-amyloid.

The findings were presented on October 26 at the 34th annual meeting of the Society for Neuroscience in San Diego, Calif.

http://www.eurekalert.org/pub_releases/2004-10/nioe-rib102504.php

Early clinical treatment can halt progression of Alzheimer's disease

A study using genetically engineered mice has provided evidence that early clinical treatment of brain lesions (by injecting anti-beta-amyloid antibodies into the hippocampus) can halt the progression of Alzheimer's disease. The clearance of amyloid plaques led to the clearance of the lesions caused by neurofibrillary tangles. The effect on neurofibrillary tangles only occurs, however, if done at a particular stage of the tangle’s growth — the earlier the treatment begins, therefore, the better the chance of success. The demonstration that early treatment of amyloid plaques stops the progression of Alzheimer’s provides support for the controversial theory that the accumulation of amyloid plaques is the initiating trigger of the disease process.

Oddo, S., Billings, L., Kesslak, P., Cribbs, D.H. & LaFerla, F.M. 2004. Aβ Immunotherapy Leads to Clearance of Early, but Not Late, Hyperphosphorylated Tau Aggregates via the Proteasome. Neuron, 43, 321-332.

http://www.eurekalert.org/pub_releases/2004-08/uoc--ect072804.php

Buildup of amyloid plaques linked to gene inhibition

Examination of genetically engineered mice and of brain tissue from deceased Alzheimer's patients has found that the buildup of amyloid plaques in the brain dramatically inhibits six genes known to be important for the formation of new memories. The finding suggests a new approach to the treatment of Alzheimer’s disease, combining amyloid-lowering treatment with other strategies designed to block the effect of amyloid on these genes.

Dickey, C.A. et al. 2003. Selectively Reduced Expression of Synaptic Plasticity-Related Genes in Amyloid Precursor Protein + Presenilin-1 Transgenic Mice. Journal of Neuroscience, 23, 5219-5226.

http://www.eurekalert.org/pub_releases/2003-06/uosf-sla062503.php

A new approach to slowing the progression of Alzheimer’s

Researchers have discovered the molecules that play a critical role in making the brain think it is under attack from the amyloid plaques characteristic of Alzheimer’s disease. Microglial cells detect beta amyloid plaques and gear up to fight them as foreign invaders. However, for some unknown reason, they don’t follow through on the attack, but remain inflamed. It is this inflammation that causes a lot of the problem. Research has now shown that the microglial cells at least four different receptor proteins to bind to the amyloid. Each one of these receptor proteins act together at the same time to drive the inflammation. This discovery suggests a new approach to treating Alzheimer’s — finding a means to block these receptors.

Bamberger, M.E., Harris, M.E., McDonald, D.R., Husemann, J. & Landreth, G.E. 2003. A Cell Surface Receptor Complex for Fibrillar b-Amyloid Mediates Microglial Activation. Journal of Neuroscience, 23, 2665-2674.

http://www.eurekalert.org/pub_releases/2003-04/cwru-mti042903.php

Gene transfer reduces levels of key Alzheimer's disease protein

An animal study has found that a molecule that naturally degrades of the protein beta-amyloid (the substance in the amyloid plaques indicative of Alzheimer’s) appears to reduce the levels of that protein by nearly 50% when delivered by gene therapy.

Marr, R.A., Rockenstein, E., Mukherjee, A., Kindy, M.S., Hersh, L.B., Gage, F.H., Verma, I.M. & Masliah, E. 2003. Neprilysin Gene Transfer Reduces Human Amyloid Pathology in Transgenic Mice. Journal of Neuroscience, 23, 1992-1996.

http://www.eurekalert.org/pub_releases/2003-03/si-gtr032003.php

Growth factor creates new neurons; may aid treatment of neurological diseases

In a series of studies, a growth factor (BDNF) was introduced into the adult rat brain, and was found to produce new neurons in various brain regions. BDNF is reduced in parts of the brain of those with Huntington’s disease and Alzheimer’s disease. These studies indicate that supplementing the adult brain with BDNF not only supports neurons in those brains, but also induces new neurons from precursor cells.

Pencea, V., Bingaman, K. D., Wiegand, S. J., & Luskin, M. B. (2001). Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus. The Journal of Neuroscience, 21(17), 6706–6717. Retrieved from http://www.jneurosci.org/content/21/17/6706

Benraiss, A., Chmielnicki, E., Lerner, K., Roh, D., & Goldman, S. A. (2001). Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain. The Journal of Neuroscience, 21(17), 6718–6731. Retrieved from http://www.jneurosci.org/content/21/17/6718

http://www.eurekalert.org/pub_releases/2001-08/sfn-nnm083101.php

Transplanted human neural stem cells improve memory in rats

Laboratory-grown human neural stem cells, the building blocks of the brain, were successfully transplanted for the first time into the brains of aged rats and dramatically improved the animals' cognitive function. The results of the study could lay the foundation for new treatments in diseases such as Alzheimer's and Parkinson's.
Neural cell transplant studies recently suffered a setback when transplanted fetal cells worsened symptoms in Parkinson's patients. However, such fetal cells are already differentiated. Laboratory-grown stem cells are not differentiated, allowing the host brain to take over, dictating where the stem cells should migrate and what types of cells they should become. As a result, the transplanted cells became functionally integrated into the neuronal circuitry of the host animal. Postmortem examination of the rats' brains demonstrated that the transplanted human brain cells had not only differentiated and were thriving in the new environment, but that the rats' own neuronal fibers had grown dramatically in areas associated with spatial memory.

Qu,T, Brannen, C.L., Kim, H.M., & Sugay, K. (n.d.). Human neural stem cells improve cognitive function of aged brain. Retrieved 27 April 2013, from http://journals.lww.com/neuroreport/Fulltext/2001/05080/Human_neural_ste...

http://www.eurekalert.org/pub_releases/2001-04/UoIa-Thns-2304101.php

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