Science and Research Questions

Niemann Pick Type C disease, a type of lysosomal storage disease, is often referred to as childhood Alzheimer's disease. It is a very rare and fatal genetic disorder in children, and those with NP-C usually do not survive past their teenager years. Because children afflicted with NP-C lack a specific protein critical for the processing and removal of complex lipids (cholesterols called gangliosides) from their nerve cells, the lipids accumulate and eventually kill the neurons. NP-C children display neurological symptoms similar to Alzheimer's disease, such as issues with balance, memory loss, and other cognitive problems. Unfortunately, there are no proven therapies for NP-C, nor is there a cure.

Valproic acid (VPA) is a drug that has been used to treat epilepsy and bipolar disorder. Researchers at Canada’s University of British Columbia in Vancouver recently discovered that VPA reduced and even slightly prevented the buildup of amyloid plaques in the brains of Alzheimer's disease-model mice when given early on in the disease. Mice given the drug also performed better on memory tests compared to mice given a placebo. VPA is thought to work by inhibiting the enzyme that produces beta amyloid, thereby preventing the accumulation of amyloid protein that becomes toxic to neurons. This study, conducted by Dr. Weihong Song, is published in The Journal of Experimental Medicine.

VPA was previously tested in Alzheimer's disease patients to assess for drug tolerability and to see whether it reduced agitation and aggression. These earlier studies did not look at VPA’s effects on brain plaques. Dr. Wong and his team are enthusiastic about the results in mice and think that the same strategy could prove effective in humans. In fact, a small clinical trial testing VPA’s efficacy on early-stage Alzheimer's disease patients is currently underway.

The gene called Apolipoprotein E (ApoE) appears to be a risk factor for the late-onset form of Alzheimer's disease. There are three forms of this gene: ApoE2, ApoE3 and ApoE4. Roughly one in four Americans has the ApoE4 gene and one in twenty has ApoE2. While inheritance of ApoE4 increases the risk of developing the late-onset form of Alzheimer's disease, inheritance of ApoE2 substantially protects against the disease.

Even though your father does not have the ApoE4 gene, you still could have inherited a copy of the gene from your mother (e.g., your genotype could be E2/E4 or E3/E4). The only way of really knowing which alleles you carry would be to perform an expensive genetic test. However, in your case the test is unnecessary because it will not tell you anything useful. Even if you were to find out that you have a single copy of the ApoE4 gene, it would only mean that you have a slightly higher risk of developing Alzheimer’s disease than the general population. Having the ApoE4 gene does not mean that a person will definitely get Alzheimer’s disease. Remember that about a quarter of the population have the ApoE4 gene—the majority of these people never go on to develop Alzheimer’s disease.

Both amyotrophic lateral sclerosis (ALS) and Alzheimer's disease are neurodegenerative disorders that cause a slow deterioration of a person’s physical and/or mental capacities. In ALS, there is loss of motor neurons mostly in the anterior horn of the spinal cord, accompanied by some inflammation and scarring (called gliosis) in the spinal cord. Alzheimer's disease is believed to be caused by a buildup of abnormally-folded proteins (amyloid and tau) that form plaques and tangles that are toxic to nerve cells, resulting in the loss of neurons in the brain.

At the molecular level, there may be a number of molecules with common or overlapping roles in either neurodegeneration or neuroprotection. For instance, oxidative stress may be at least partially the cause of neuronal cell death observed in both ALS and Alzheimer's disease. One molecule that has been proposed to play a role in this oxidative damage in both diseases is the enzyme Cu,Zn-superoxide dismutase (SOD1). Scientists are aware of certain mutations in the SOD1 gene that can cause familial ALS, and some studies have found the SOD1 protein to be aggregated with beta amyloid in plaques within Alzheimer's disease patients’ brains.

On the flip side, a molecule that may provide protection to neurons is SIRT1. The SIRT1 molecule was found to be upregulated in the brains of mice that were mouse models for Alzheimer's disease and for ALS, as well as in non-diseased neuronal cell cultures subjected to neurotoxic insults. Addition of SIRT1 or resveratrol (a SIRT1-activating compound) to these neuronal cell cultures was found to be neuroprotective, promoting the survival of the cells. These are but two of the many molecular links between the two diseases; there are probably dozens more links still waiting to be uncovered by scientists.

While it is rare, early-onset Alzheimer's disease can occur in an individual with no known family history of the disease. Less than 10 percent of all Alzheimer's disease cases are of this type.

There are many things that could be contributing to your lapses of memory—it may be premature to think it’s due to Alzheimer's disease. Have you been under an excessive amount of stress lately? Have you started taking any new medications? Do you get enough B12 vitamins? Are you in any way depressed? Believe it or not, stress, depression, B12 deficiency, interactions between medications (or side effects from a new drug), hypothyroidism, viral infections, etc.—can cause memory problems, confusion, and mood swings (all of which are also early symptoms of dementia). Because of the nature of your memory problem, I suggest you see your physician for a thorough examination.

According to the Alzheimer Society of Ireland, over 40,000 people in Ireland currently have dementia, and Alzheimer's disease accounts for half of these cases. Dementia affects approximately 5% of the population in Ireland over the age of 65 and 20% of the Irish population over 80 years of age. This year alone (2008), an estimated 4,000 new cases of dementia will be reported. And it is also estimated that by the year 2036, the number of dementia cases in Ireland will increase over 300 percent.

The Alzheimer Society of Ireland reports that family caregivers provide just over half (57%) of the value of informal care without compensation, with less than 10% of support coming from community care services. Because of the expected increase in patients with dementia over the next few decades, the Alzheimer Society of Ireland has made it a priority to increase government funding for community based services, research, early diagnosis and intervention, and education. Ireland is not alone in this dementia epidemic. Governments in all nations where care for patients with dementia is escalating at an ever-alarming rate would be wise to invest in sound preventative, diagnostic and management strategies.

The vagus nerve is a cranial nerve that originates in the brain and innervates the heart, lungs, gut, adrenals, and other organs and glands in the chest and abdomen. Vagus nerve stimulation (VNS) – which entails electrical stimulation by a device surgically implanted in the neck – has been used to treat refractory epilepsy and treatment-resistant depression. Because some studies have suggested that VNS might improve memory and cognition, a recent study looked at whether VNS could be used to help Alzheimer's patients. The study found that in 17 patients with probable Alzheimer's disease given VNS, about 40 percent of the patients improved and 70 percent did not decline mentally as measured by standard Alzheimer's disease cognitive assessment scales. Moreover, the investigators found that VNS was safe and well-tolerated even after one year of treatment. Further studies on VNS therapy for Alzheimer's disease are obviously warranted.

The study did not, however, indicate the mechanism by which vagal stimulation affected cognition. The researchers did not examine acetylcholine production or release by the vagus, so it is not possible to say whether or not this was a factor in helping these patients.

Patients suffering from Alzheimer's disease (AD) have low levels of acetylcholine in their brains, an important chemical involved in nerve cell communication. I am not aware of supplements or drugs that specifically stimulate the vagus to produce acetylcholine, and at present there are no studies to indicate that such drugs could be used to treat AD patients. But there are medications that help to maintain acetylcholine levels in the brain. These drugs, called cholinesterase inhibitors, slow the metabolic breakdown of acetylcholine and make more of this chemical available for communication between neurons. Cholinesterase inhibitors such as galantamine (Razadyne), rivastigmine (Exelon), donepezil (Aricept), and tacrine (Cognex) have been approved by the Food and Drug Administration (FDA) for the treatment of AD and are designed to regulate its symptoms and delay its course.

Unfortunately, there currently is no way to entirely prevent Alzheimer's disease. However, research findings suggest that the best approach to reducing your risk of developing Alzheimer's disease involves a combination of measures such as eating a healthy diet that is low in saturated and trans fats, and staying active with regular physical and mental exercise for your body and brain.