Causes of Alzheimer’s Disease

The causes of Alzheimer’s disease are still in question, and the changes that take place in the brain are constantly being studied.  There are several theories about the causes underlying Alzheimer’s disease including:

1. The brain doesn’t make enough acetylcholine, a neurotransmitter.

2. Beta amyloid, shortened forms of a protein, join together to form plaques in the brain.

3. Myelin, an insulating material that surrounds neurons, breaks down.

4. Tau tangles form in the brain.

Let’s discuss that last theory, the tau theory, in more depth.  The tau protein interacts with and stabilizes microtubules, the scaffolding structure of cells.  It is found mostly in neurons.  Two different changes in the tau protein can affect its ability to function normally – isoforms and phosphorylation.

Different isoforms of the tau protein can be present in cells.  Isoforms of tau are different versions of the protein.  They are made when the gene from which the protein is created is cut in various places creating different sequences.  These isoforms have variable structures with different attributes.  Some of the isoforms of tau are more likely to form tangles than others.

The tau protein can also be changed after the protein is made through a process called phosphorylation.  Phosphorylation adds a phosphate group to the tau protein.  If several phosphate groups are added to the protein, tau can self-assemble into the tangles that are characteristic of Alzheimer’s patients.

Tau protein aggregates into filaments (left).  The filaments form tau tangles (right).

Tau tangles can lead to disintegration of microtubules in neurons.  This can then result in malfunctions in the communication between neurons leading to cell death and cognitive impairment seen in Alzheimer’s patients.

Memories of Grandma

I had another post planned for this week, a post about Alzheimer’s research and new advances in the field.  But on April 1st, I got a phone call.  My grandmother, who has been living with Alzheimer’s for several years, was getting moved to hospice and was not doing well.

The past nine days have been spent visiting her at hospice, hoping for peace and comfort to find her, spending time with aunts, uncles, and cousins, and remembering the grandma we all once knew.

The grandma we remember was the woman who would organize a gigantic garage sale every Memorial Day at their cottage home on the lake.  The woman who would cook in the tiny kitchen at the cottage and feed anyone and everyone who walked through the door.  The woman who would make the world’s best crepes and the most fantastic caramel brownies.  The woman who raised eight kids, took care of her husband, and entertained grandchild after grandchild and never seemed to grow tired.  The woman who always had a kind word and a hug at the ready.

I won’t let Alzheimer’s take my memories, and I will remember the strong, incredible, beautiful woman my grandmother will always be to me.  Even if she has forgotten.

The Costs of Alzheimer’s Disease

Alzheimer’s disease affects 5.3 million people in the United States, and it is the 7^th leading cause of death.  In Wisconsin alone, 110,000 people currently live with Alzheimer’s.  Despite its prevalence, effective treatments and cures have yet to be found.  Due to the lack of therapies, those diagnosed with the disease often require long-term care, and Alzheimer’s care is a significant cost for patients, the state, and the country.

While older Americans make up about 12 percent of the population, they account for 90 percent of nursing home residents.  In 2010, Alzheimer’s costs reached $172 billion dollars.  Additionally, there are an estimated 10.9 million unpaid caregivers in the US providing around 12.5 billion hours of care.  This contribution was valued at almost $144 billion, $2.6 billion in Wisconsin alone.

Long-term care and other Alzheimer’s costs are paid by a variety of sources including Medicare and Medicaid.  In 2004, Medicare costs per Alzheimer’s patient ($15,145) were almost three times higher than costs for other Medicare recipients of the same age ($5,272).  That same year, 28 percent of Medicare recipients aged 65 or older also received Medicaid benefits.  Medicaid payments per Alzheimer’s patient ($6,605) were more than nine times higher than payments for other elderly people of the same age ($718).

Although Medicare, Medicaid, and other funding sources provide support for much of Alzheimer’s care, patients and families still must pay high out-of-pocket costs.  These costs include premiums, co-payments, and services that are not covered by other sources.  In 2004, out-of-pockets costs for Medicare recipients with Alzheimer’s averaged $2,464.  Average out-of-pocket costs for patients living in nursing homes or assisted living facilities were significantly higher at $16,689.

Another cost accrued by Alzheimer’s patients is hospice care.  The average length of stay for hospice patients with a diagnosis of Alzheimer’s was 105 days in 2008.  Total payments for hospice care from all sources totaled $2.8 billion in 2004 with per person payments averaging $976 (compared to $120 per person for patients without Alzheimer’s).

Because the costs of Alzheimer’s care is so high, and because the aging of the baby boomer generation is expected to greatly increase the number of Alzheimer’s patients, strategies for decreasing Alzheimer’s care costs is necessary.  This decrease could be achieved by shortening the disease course through earlier detection of the disease and more effective treatments.  With these improvements, treatments would slow cognitive decline, delay the age at which the disease appears, and increase the years that Alzheimer’s patients can remain at home.

In a 2009 paper, two Wisconsin researchers addressed this issue and calculated the potential cost savings if early detection and treatment of Alzheimer’s were possible.  Using a statistical analysis, the authors found that early detection and effective treatment of a 70-year-old woman with mild cognitive impairment would lead to $5,000 in state savings and  $10,000 in federal savings.  When a program of caregiver support was added to early detection and treatment, the analysis yielded even higher savings.  The authors stated that, by their calculations, the state savings were higher than the cost of implementing an early diagnosis program.  Therefore, if the state paid all costs of implementing an early detection and caregiver intervention program not covered by federal funds, the state would still save approximately $10,000 per diagnosed patient.

Currently, there is little incentive for caregiver support.  This paper concludes that the lack of support for family and friends is fiscally irresponsible.  With the development of caregiver support programs, patients could remain out of nursing home care for a longer period of time, thus significantly decreasing long-term care costs.

The high costs of Alzheimer’s care will continue to rise as people live longer and baby boomers approach the age at which Alzheimer’s is diagnosed.  In addition to the impact on Medicare and Medicaid spending, out-of-pocket costs put another stress on patients and caregivers.  With the current economic climate across the country, cuts in support for Alzheimer’s care may become necessary.

However, many studies are now focusing on the ability to detect and treat Alzheimer’s early, before cognitive decline can be measured.  Through earlier detection, more effective treatment, and additional support for caregivers, the costs of Alzheimer’s care for the state, the country, and families would decline.  Such a program would also provide hope and reassurance to those affected by a disease currently surrounded by uncertainty.

Data for this post provided by the Alzheimer’s Association.

Imaging Brain Changes in Alzheimer’s Disease

Alzheimer’s research aims to decrease some of the uncertainty surrounding causes, diagnosis, and treatment of the disease.  Many researchers believe that an important aspect of treatment will involve identifying the disease early and treating those early changes in the brain.

Beta-amyloid plaques are aggregates found in the brain of Alzheimer’s patients. Historically, these plaques were only identifiable upon autopsy.

A beta-amyloid plaque

Recently, better techniques for imaging these plaques have been developed.  As techniques improve, more information about the effects of the development of the disease on the brain can be gathered.

In a recent paper in Brain: A Journal of Neurology (published online February 9^th), Gael Chetelat and colleagues use imaging techniques to more fully recognize early brain changes in Alzheimer’s progression and how those changes relate to memory decline.  Using magnetic resonance imaging (MRI), the researchers image and recognize a portion of the brain called grey matter.  They also use positron emission tomography (PET) to visualize a tracer that marks beta-amyloid deposits.  They aim to relate the breakdown of brain matter and the location of beta-amyloid plaques to the degree of memory loss in patients in the pre-dementia stage of Alzheimer’s disease.

The researchers find that memory performance of patients in the pre-dementia stage relates to two changes in the brain.  The first change is increased beta-amyloid deposition, specifically in the temporal neocortex.  The temporal neocortex is part of the outer layer of the brain located on either side, and it plays a critical role in visual processing, storage of language, and memory.

Labeling of temporal beta-amyloid deposition (left) and location of reduced grey matter in the hippocampus (right)

The second change in the brain is a decrease in grey matter in the hippocampus.  The hippocampus is located inside the brain structure with mirror-image halves in the right and left sides of the brain, and it is important in navigation and long-term memory.  The authors suggest that these insults to the brain structure should be considered separately as researchers look for possible targets of therapies.

The prospect of imaging specific changes in brain structure is exciting.  If these changes can be related to future Alzheimer’s progression or other forms of memory loss (which the authors caution cannot be done from their study), early identification of these insults may allow time for intervention and treatment that can slow or stop memory loss.  Knowledge of the specific locations of the insults as well as improvements in the techniques available to image the brain will be invaluable advances in the fight against dementia and Alzheimer’s.

Beta-amyloid photo here.  MRI photos from Chetelat study here.