Welcome back to the Carbohydrates Can Kill Show on Alzheimer’s Disease and Carbohydrates. I am Robert Su, M.D. Let’s continue the discussion about history of dementia.

Alzheimer’s disease or AD is another of the most common types of dementia among older people nowadays. According to history, during the ancient time, dementia was linked to old age because it was observed mostly among older people who were 65 years of age or older. In 1901, a German psychiatrist, Alois Alzheimer identified a case of dementia in a woman, and followed her up till 1906 when she died. Dr. Alzheimer reported this case in detail. Because of that, this disease was named after him. This disease is regarded as senile dementia. Years later, a subtype of this disease found in the younger population and was named as presenile dementia. During the 20^th century, Alzheimer’s disease was used for all the cases, which shared similar clinical and pathological manifestations regardless of the patient’s age.

Alzheimer’s disease, as described earlier, progresses slowly with loss of cognitive functions. Recent studies have shown that accumulation of beta-amyloid plaques in the brain is the characteristic pathological finding. It is thought that the plaques built up surrounding the neurons or nerve cells cause these neurons or nerve cells to lose their functions. Consequently, the victim of Alzheimer’s disease loses his cognitive functions. I’ll discuss more about its possible cause or causes and pathological findings later.

It is interesting to note in my discussion earlier about the causes of dementia that include changes in blood sugar, sodium, and calcium levels, and use of certain medications including cimetadine, and some cholesterol-lowering drugs. Cimetadine is an antacid drug. In fact, studies have linked the prevalence of Alzheimer’s disease to those who are diabetics or have a low level of serum cholesterol.

In the January-February 2005 issue of Psychosomatic Medicine, Elias PK et al published an article, “Serum cholesterol and cognitive performance in the Framingham Heart Study.” They followed 789 men and 1,105 women from the Framingham Heart Study who were free of stroke or dementia and received biennial total cholesterol evaluations for a surveillance period of 16 to 18 years. Four years after the surveillance, these participants underwent cognitive tests. They demonstrated a positive leaner relationship between the readings of total serum cholesterol and the performance of cognitive functions. Those whose total cholesterol were at 240 mg% performed the best, and followed by those whose total cholesterol were 200-239 mg%, and 200 mg% or less, respectively.

For at least the past two to three decades, we have been bombarded with the hypes that fats, which include cholesterol and triglycerides, are responsible for cardiovascular diseases, particularly coronary artery disease and atherosclerosis. Organized medicine has continued to scare us with the horrors of having a high level of cholesterol and further to brainwash us with the benefits of a low cholesterol level that would prevent coronary artery disease and atherosclerosis. It has urged us to restrict dietary fats including both cholesterol and triglycerides, and to use statin drugs for lowering our serum cholesterol levels.

To our disappointment, organized medicine has forgot to let us know that dietary cholesterol and triglycerides provide only a small fraction of total serum cholesterol and triglycerides. The majority of fats or cholesterol and triglycerides are produced by the liver with the abundant supply of glucose from excess carbohydrate foods. Non-alcoholic fatty liver is the prime case in point for the consequence of consuming diet high in carbohydrate and low in fat.

Besides, cholesterol is a major component of cellular membrane, especially important in maintaining cellular functions including the conduction of signals by neurons or nerve cells. The endless efforts in lowering the serum cholesterol level may contribute into the unfortunate health consequence — the increasing prevalence of Alzheimer’s disease nowadays.

Recent studies have also revealed the association between diabetes mellitus and the prevalence of Alzheimer’s disease. Yutaka Kiyohara, MD, PhD, of Kyushu University in Fukuoka, Japan, and associates reported in the September 20, 2011 issue of Neurology that, in their 15 years of follow-up, diabetic patients were 74% more likely to develop any types of dementia. And diabetic patients were 2.5 folds more often to develop Alzheimer’s disease than those who had normal glucose tolerance.

In the February 2004 issue of Diabetes, Janson J et al published an article, “Increased Risk of Type 2 Diabetes in Alzheimer Disease.” The article notes that both Alzheimer’s disease and type 2 diabetes share similar characteristics that include “increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in

the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes).”

Based on the clinical data and pathological study from the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), Janson and associates found, that among a total of 100 participants who suffered with Alzheimer’s disease, 81 had either type 2 diabetes or IFG (Impaired Fasting Glucose). Over a period of 10 years, the mean slope of increase of FPG (Fasting Plasma Glucose) was also greater in Alzheimer disease than non–Alzheimer disease control subjects. In autopsy, amyloid found in the Langerhans islet of the pancreas was “more frequent and extensive in patients with Alzheimer disease than in non–Alzheimer disease control subjects.” The degree of diffuse and neuritic plaques was positively correlated with the duration of type 2 diabetes. With these findings, the prevalence of Alzheimer’s disease is increased in those with diabetes mellitus and impaired fasting blood glucose concentration.

One important point that I wish to stress here is that 19 participants with Alzheimer’s disease had neither type 2 diabetes nor impaired fasting blood glucose concentration. Because of such cases, a group of researchers thought Alzheimer’s disease might be a type of diabetes mellitus solely involving the brain but not the pancreas. Thus, they proposed to name Alzheimer’s disease as type 3 diabetes mellitus. However, those patients had likely had repeated postprandial hyperglycemia, which sufficed for developing Alzheimer’s disease, but their blood tests might not meet the diagnostic criteria for diabetes mellitus or pre-diabetes. These situations are also found in the cases such as retinopathy and the diseases, which are strongly linked to diabetes mellitus as co-morbidities.

Before I begin to discuss the cause or causes of Alzheimer’s disease, let me recapture its clinical description here.

Generally, Alzheimer’s disease or AD is regarded as an age-related and slowly progressive disease, which is considered non-reversible with a poor prognosis. Its cause or causes are still unclear, despite that there are several emerging hypotheses and pathological findings that continue to help understand this puzzling and yet detrimental disease.

Clinically, patients with Alzheimer’s disease would initially notice some memory loss and a bit of confusion at times. Gradually, they would have problems in language skills, reasoning, decision-making, recognizing their surrounds and people including their own family members. Their family members and friends would notice changes in their behaviors and personalities. Eventually, their symptoms would worsen. Alzheimer’s disease would lead them to a major loss of mental functions.

Although Alzheimer’s disease is age-related, studies have indicated that the disease begins to develop at a much younger year, around the 30’s or 40’s of age. This constitutes a major challenge in psychiatric practice, which needs to differentiate those young adults who are diagnosed with psychiatric disorders from those who are about to develop Alzheimer’s disease and change their behaviors and personalities.

We’ll be back in a moment.