For those of us who lobby for resources, it is no overstatement to say that Alzheimer’s disease has reached crisis proportions in the United States.

As we are getting older, the incidence, prevalence and mortality of Alzheimer’s disease are all rising.

The 2007 Alzheimer’s Disease Facts and Figures report by the Alzheimer’s Association makes sobering reading. Here are some of the headline facts:

• Alzheimer’s disease is the most common cause of dementia
• At the present rate, one in 85 people will have the disease in 40 years
• There are now more than 5 million people suffering from Alzheimer’s disease, and the report projects an increase of 16 million cases by 2050 unless preventive measures are taken and/or science is able to come up with a prevention or cure
• One person is now diagnosed with dementia every seven seconds
• One in every four American families is affected by dementia
• The incidence of dementia is one in 1,000 before age 65 and one in 20 after age 65.
• More than $100 billion is spent per year on dementia, which is about 10 percent of all healthcare expenditures

As we have discussed before, the symptoms of dementia may be delayed for 3 to 5 years through healthy lifestyles and behavior modification, and there are many new treatment approaches in the pipeline.

The huge issue is that statistic about one in four families being affected by the disease. And it is a disease: it is not part of normal aging.

Caregivers can suffer terribly.

The Alzheimer’s Association also has some information for those who care for people with Alzheimer’s.

There is also some food information here concerning caregiver stress.

I would also like to direct you to some of the things that I have written here about the wellness of caregivers.

And for everyone, don’t wait until you are thirsty before you dig that well. Work on building you personal resilience and follow the simple lifestyle guidelines that may significantly reduce your risk of developing Alzheimer’s disease.

Alzheimer’s disease remains a puzzle.

Although there are plenty of people who claim that “The Cause” of Alzheimer’s is… and here you can take your pick of three-dozen theories.

The truth of the matter is that simple explanations - Aluminum, lead, stress, pollution, mycoplasma infections and the rest – fail to explain many of the established observations about the causes of the disease.

From what we know about the genes in the brain, it is highly likely that “Alzheimer’s disease” represents a group of disorders that follow an interaction of sets of genetic and environmental factors.

This notion is supported by a report from investigators at Washington University School of Medicine, St. Louis and several other prominent research centers. The study is published in today’s issue of the journal Neuron and indicates that there a biological link between a protein mutation that causes early-onset Alzheimer’s disease (AD) and a gene variant linked to late-onset AD.

The investigators tried to link the function of two known causative factors in AD. Mutations in amyloid precursor protein (APP) cause early-onset Alzheimer’s disease (AD), but
the only genetic risk factor for late-onset AD is the ɛ4 allele of apolipoprotein E (apoE), a major carrier of cholesterol in the circulation and in cell membranes.

Previous research has shown that mutations in APP can cause early-onset AD when the protein is “cleaved” or split, producing a short toxic protein that builds up in the brain and kills neurons.

In their experiments with mice and cultured mouse cells, the researchers linked APP to the regulation of apoE and its cholesterol transport function. They found that the normal cleavage of APP in the cell gives rise to a nontoxic fragment (called AICD) that suppresses the gene that produces the cell receptor for apoE, known as LRP1. Crouching in nerve cell membranes, this receptor enables the apoE protein to transport its cholesterol cargo into the cell.

The researchers speculated that the loss of LRP1 function in AD might cause a loss of cholesterol that causes malfunction of neurons.

These observations may turn out to be extremely important. If we can restore the activity of the receptor gene, we might have a new treatment strategy for AD.

I have a keen interest in healthy aging, and we have talked before about some of the strategies that can help protect you against developing cognitive decline.

New research now shows for the first time that, of all lifelong activities, only a high level of mental or cognitive activity protects against the devastating memory loss of Alzheimer’s disease. High levels of social or physical activity are not enough.

Researchers from the Byrd Alzheimer’s Institute bred mice that are genetically predisposed to developing the pathological changes of Alzheimer’s diseases in their brains.

They then kept the mice in one of four housing environments — high social activity, high physical activity, high cognitive activity, or a single housing control environment and watched them from young adulthood through old age.

When the researchers tested the mice in a battery of memory tasks in old age, only the mice given a lifelong high level of cognitive activity were protected against memory impairment. In fact, these “high cognitive activity” mice performed as well as normal mice that do not develop Alzheimer’s disease. However the Alzheimer’s mice raised in one of the other three environments performed poorly in multiple memory tasks.

Not only was memory protected in Alzheimer’s mice by a high level of cognitive activity, but also brain levels of the abnormal protein beta-amyloid were substantially reduced. This protein, thought to be key for Alzheimer’s development, remained at soaring levels in the brains of Alzheimer’s mice raised in social or physical activity environments. Moreover, the researchers found that only the Alzheimer’s mice raised with high cognitive activity had an increase in connections between brain cells. Alzheimer’s mice raised in one of the other three housing environments had much fewer connections between their brain cells.

The new study is published in the Neurobiology of Learning and Memory Journal.

The lead researcher is Gary Arendash, and he had this to say:

“Our results call into question the earlier human studies suggesting social or physical activity provides protection against Alzheimer’s. Alzheimer’s begins in the brain several decades before any symptoms´ show up. That means adults in their forties and fifties need to make lifestyle choices now to decrease their risk of getting Alzheimer’s disease later.”

This is all correct, but there is still an important question: can we really extrapolate from mice to humans? Mice are social creatures, but not to the same extent as humans beings. The lion’s share of the human brain is dedicated to social activities, so you would expect that social activities will be particularly important in the maintenance of the human brain.

Insulin may have some extremely important roles in the mind as well as the body.

Though best known for its role in promoting glucose uptake into cells, insulin has at least five hundred known functions in the human body. For many years nobody was sure whether insulin was important to the brain: neurons in the brain are unusual in that they do not need insulin to enter them. But then we discovered that insulin acts on other important metabolic processes in neurons. In the brain it also does duty as a chemical messenger and as a growth factor, and brain insulin signaling is crucial for the creation of memory. Over the years a number of theorists have suggested that some neurological and psychiatric illnesses could be a result of disturbances in insulin-related processes in the brain.

It is now beginning to look as if they may have been correct.

Some recent evidence has suggested that Alzheimer’s disease and diabetes mellitus share a number of common pathways and Alzheimer’s disease is associated with peripheral insulin resistance.

New research has been published by investigators from Northwestern University in the FASEB Journal - the journal of the Federation of American Societies for Experimental Biology – that may finally nail down the reason why insulin signaling may stop working in Alzheimer’s disease.

The research team used mature cultures of neurons from the hippocampus of the brain to study synapses – the connection between neurons - that have been implicated in learning and memory mechanisms. They wanted to examine the effect of a toxic protein, known to attack memory-forming synapses, that is called “ADDL” for “amyloid ß-derived diffusible ligand.” ADDLS are small, soluble aggregated proteins that accumulate in the earliest stages of Alzheimer’s disease. The researchers had previously found that ADDLs bind very specifically at synapses, which in turn initiates deterioration of their function, shape and composition. They now went on and studied the synapses and their insulin receptors before and after ADDLs were introduced. Regions of the nerve with normal numbers of insulin receptors have no ADDL binding, but when the ADDLs are added they remove insulin receptors from nerve cells, effectively making them insulin resistant.

And an insulin resistant neuron cannot participate in the formation of memories.

This finding implies that there is a fundamental connection between diabetes and Alzheimer’s disease, and this may in turn help us to see whether existing diabetes treatments might protect neurons from ADDLs and improve insulin signaling in people with Alzheimer’s disease.

The first type of diabetes is Type 1, a.k.a. insulin-dependent or juvenile onset. The second is Type 2, a.k.a. non-insulin-dependent diabetes. So is Alzheimer’s Type 3?

It has also been known for some time that physical exercise is one of the factors that may help reduce the chance of developing Alzheimer’s disease, and we may now have a mechanism by which it can help.

This is an extraordinarily interesting and important discovery that should lead to a whole new research angle, perhaps with medicines that are already available.

There is a fascinating study by colleagues from University College London (UCL) that has just been published in the Proceedings of the National Academy of Sciences that has found a “clear link between what causes Alzheimer’s and one of the basic mechanisms behind glaucoma.”

The research could speed up the development of new treatments for Alzheimer’s and revolutionize the treatment of glaucoma, the most common cause of blindness in the Western world.

If glaucoma is indeed confirmed as a marker or risk factor for Alzheimer’s then the early warning signs it gives could help ensure that patients have more opportunities to delay the onset of dementia.

The researchers discovered that the same “plaque” proteins are a key process in the development of both diseases. Clumps - or plaques - of beta-amyloid proteins that kill brain cells in Alzheimer’s patients, also kill optic nerve cells in the eyes of glaucoma sufferers. A link has bee suspected for some time: around 1.8-2.0% of the population will develop glaucoma, the figures in Alzheimer’s is as high as 25%.

Dr Francesca Cordeiro, who led the team at UCL’s Institute of Ophthalmology, said:

“We’ve seen for the first time that there is a clear link between what causes Alzheimer’s and one of the basic mechanisms behind glaucoma.”

Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. People with glaucoma gradually lose their wider field of vision. Many do not realize it until they barge into things.

The textbooks will tell you that glaucoma is caused by increased pressure in the eye, known as intraocular pressure. Standard treatments attempt to lower this pressure, but with only limited success. People with normal pressure can also suffer from glaucoma, suggesting it is not the only cause.

The researchers have shown that drugs that prevent the build-up of “plaque” proteins in the brains of people with Alzheimer’s disease were successful in treating glaucoma in rats. One such drug, bapineuzumab, is already being used to treat Alzheimer’s patients in clinical trials in Britain and the United States.

The UCL researchers showed that the effects on glaucoma were even stronger when combined with two other novel Alzheimer’s treatments - “Congo Red” and a drug called a beta-secretase inhibitor.

This is very exciting work and we should know fairly soon whether these new approaches to treatment will help both glaucoma and Alzheimer’s disease.

Clearly this does not mean that everyone with Alzheimer’s will develop glaucoma or vice versa. Both problems have multiple causes and can follow quite different trajectories. But links like these are the stuff of medical progress.