Alzheimer dementia and diabetes

Alzheimer’s disease [AD] is the most common cause of dementia in North America. Despite 30+ years of intense investigation, the field lacks consensus regarding the etiology and pathogenesis of sporadic AD, and therefore we still do not know the best strategies for treating and preventing this debilitating and costly disease. However, growing evidence supports the concept that AD is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor [IGF] stimulation. Moreover, AD is now recognized to be heterogeneous in nature, and not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides and hyperphosphorylated tau. Other factors, including impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to AD. Herein, the contributions of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism are reviewed. In addition, we discuss current therapeutic strategies and suggest additional approaches based on the hypothesis that AD is principally a metabolic disease similar to diabetes mellitus. Ultimately, our ability to effectively detect, monitor, treat, and prevent AD will require more efficient, accurate and integrative diagnostic tools that utilize clinical, neuroimaging, biochemical, and molecular biomarker data. Finally, it is imperative that future therapeutic strategies for AD abandon the concept of uni-modal therapy in favor of multi-modal treatments that target distinct impairments at different levels within the brain insulin/IGF signaling cascades.
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Alzheimers disease is a silent epidemic in Northern climates such as Upstate New York.

‘Silent epidemic’ already striking Western New York

Joseph Giel, 90, closes his eyes to recall something while he takes a mini-mental status exam at the UC Davis Alzheimer’s Disease Center in Sacramento, Calif. Past testing has shown Giel to be in good cognitive shape.Joseph Giel, 90, closes his eyes to recall something while he takes a mini-mental status exam at the UC Davis Alzheimer’s Disease Center in Sacramento, Calif. Past testing has shown Giel to be in good cognitive shape. McClatchy Newspapers
By Melinda Miller | News Staff Reporter | Google+
on May 30, 2014 – 7:30 PM

The first winds of the “silent epidemic” of dementia already are hitting Western New York and it will get worse before it gets better, local observers say.

“In the eight Western New York counties, we estimate about 55,000 people have Alzheimer’s or another form of dementia,” said Leilani Joven Pelletier, executive director of the regional chapter of the national Alzheimer’s Association. “We’re an older community here, which naturally increases our prevalence of the illness a little bit.”

The state Health Department expects the number of dementia patients to increase by about 8 percent by 2020, and by 2025, when the front line of the “gray tsunami” of baby boomers reaches 74 – the average age of onset for Alzheimer’s – the increase will be 20 percent.

But there is no need to look ahead. The demand for help and treatment is already here.

The Alzheimer’s Disease and Memory Disorders Center, a clinic and research facility operated through the University at Buffalo’s neurology department, opened in late 2011 on the Buffalo Niagara Medical Campus and already has a satellite clinic in Williamsville.

Dr. Kinga Szigeti, director of the center, said that the clinics have seen a change in their clientele in the short time they have been open, and she credits a better-informed public for the difference.

“Initially, the patients were largely people in mid to advanced stages of Alzheimer’s, but now we are getting more people with mild symptoms that might respond better to treatment,” she said. “With current medications we can change the slope of the decline. This is a very good change in our clinical practice.”

The success of early treatment in slowing the illness has helped some people overcome their avoidance of seeing a physician and receiving the frightening diagnosis.

“People realize that the decline rate can be cut in half,” Szigeti said. “With treatment, people are staying in ‘mild’ stages for many years. They can go to their grandchildren’s graduations, they can be active, they can be happy. Just by coming in early, the nursing home could be delayed by as much as two years.”

Delay, however, does not mean cure, and right now no cure exists.

“As far as science knows right now, exercise, healthy eating, lifelong learning, those types of things may reduce the incidence of Alzheimer’s somewhat, but the real risk factor is age,” said Pelletier of the Alzheimer’s Association.

Because the illness attacks the brain and memory functions, she said, it is believed that the best way to stave off its effects is by managing other diseases that affect brain function: heart disease, diabetes, high blood pressure.

International studies support those recommendations. ““New Insights Into the Dementia Epidemic,” a report in the February New England Journal of Medicine, evaluated the results of several research projects that indicate while the actual numbers of dementia cases will almost certainly increase as more people reach old-old age (over 80 years), the percentage of cases appears to be going down by as much as 4 percent.

The decrease was attributed to a generally healthier, better educated population and particularly to a measured reduction in vascular disease – meaning heart problems and stroke.

That remains only part of the puzzle, however.

At the UB center, researchers are focusing on the hereditary indicators for dementia.

“Genetics is a very useful tool to crack this disease,” Szigeti said. “Alzheimer’s is highly heritable – about 70 percent of cases.”

By defining genetic markers for the illness, she said, researchers and ultimately physicians will be able to tailor treatments to individual patients.

“It won’t be one simple solution,” Szigeti said. “It will be part of the battery of factors we consider. I imagine treatment will turn out like what we do for colon cancer: you turn 50 and get a colonoscopy. With this, you go in at 65 and get your dementia testing.”

Those tests could involve simple cognitive exercises, genetic evaluation of skin cells and even the “smell” test. Part of the UB research is examining olfactory receptors in the genome – Szigeti explained there are “smell receptors” on every chromosome – to look for correlations between variations in the receptors and the effectiveness of dementia medications.

That is just one of many problems researchers hope to solve. For all of them, though, one of the biggest difficulties continues to be funding.

UB has received money from the National Institutes of Health, the Alzheimer’s Association, the Community Foundation for Greater Buffalo along with other smaller grants, Szigeti said, and more would be better. She noted that, since the federal cutbacks, NIH funding has been cut about 74 percent, from the top 20 proposals to the top five.

“Money always helps. It accelerates the research. If I have four people working, and can add a fifth person to help analyze the data, it could go 20 percent faster,” she said.

Pelletier was even more blunt about the facts of funding.

“Alzheimer’s costs this country $214 billion per year,” she said, “and the government gives $566 million to research (about 0.25 percent).”

“The kind of movement we need is not going to come from some office in the capital. People need to start it,” she said.

For right now, families and individuals looking for help dealing with Alzheimer’s can call UB’s Alzheimer’s Disease and Memory Disorders Center at 859-3484 for information about treatment or to participate in research. For help in coping with the symptoms and day-to-day aspects of the disease, call the Western New York chapter of the Alzheimer’s Association at (800) 272-3900. Counselors there can offer advice on interacting with an Alzheimer’s sufferer, home security measures that are available to protect patients, and support groups for both patients and caregivers, among other things.

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Autoimmune disease, inflammation and the brain

Went to a fabulous lecture by  Dr. Souhel Najjar on autoimmune encephalitis this morning. As a reminder, bad relationships (including with one’s self-image etc.) can also cause/contribute to inflammatory burden. Below is a well-informed and written piece on Anti-NMDA-receptor encephalitis … Continue reading

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Low male sex hormones (“Low T”), heart attack risk, and social status

There has recently been more buzz around “low-T” and heart attack/stroke risk. Not usually mentioned is the fact that “T” (testosterone) is a social hormone (most hormones are). Low social status lowers “T”. Injecting/supplementing T without proper attention to the psychology of the situation may make things worse. Continue reading

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Association of Childhood Adversities and Early-Onset Mental Disorders With Adult-Onset Chronic Physical Conditions

Important paper on childhood adversities an adult-age chronic medical conditions, published just before our study on endogenous opioid dysregulation after early childhood adversity in psychiatrically and physically “healthy” adults.   Archives of General Psychiatry August 2011, Vol 68, No. 8 > < Previous ArticleNext … Continue reading

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