~Mild Cognitive Impairment

~Mild Cognitive Impairment
Reprinted with permission of Life Extension®.

Nutrition to Stay Sharp

It is estimated that up to one third of adults will experience a gradual decline in cognitive function known as mild cognitive impairment as they age (Low LF et al 2004; Busse A et al 2003). Less severe than dementia, mild cognitive impairment is defined as cognitive defects that do not interfere with daily living. It may include slower thinking, a reduced ability to learn, and impaired memory. While many conventional physicians view these defects as an inevitable consequence of aging, newer research has uncovered possible reasons for mild cognitive impairment and has also identified potential therapies that may enable people to battle age-related mental decline more effectively than ever before. Minimizing cognitive defects will become even more important as the average life span continues to lengthen and hundreds of thousands of people head into their 80s and 90s, when the risk for cognitive decline is greatest.

Researchers have discovered multiple factors that influence our ability to think and remember as we age. These include well-known culprits such as alcohol abuse, and also newly discovered causes of mental decline, including chronic inflammation, vascular diseases, and even stress.

Physical changes that occur in the aging brain are also implicated in mild cognitive impairment. For example, the number of nerve impulses and nerve cells decreases with age (Beers MH et al 1999). Also, levels of neurotransmitters such as serotonin and acetylcholine, a primary transmitter for learning and memory, decrease. This loss of acetylcholine was noticed three decades ago, giving rise to a theory that coupled the loss of acetylcholine with cognitive decline. Once acetylcholine had been identified as a possible target for improving brain function, researchers began looking for ways to boost acetylcholine levels. At least three supplements have been discovered that do just that.

Blood flow to the brain is also an important factor in brain health. Blood delivers the oxygen and nutrients necessary for normal functioning. Unfortunately, even during normal aging, blood flow to the brain may decrease by an average of 20 percent. The decreased blood flow that results from aging and associated diseases can cause nerve cells in the brain to be lost prematurely. This loss may contribute to the decline of cognitive function (Beers MH et al 1999).

Possible Causes of Mental Decline

Of course, the best strategy for treating mild cognitive impairment is to avoid it in the first place. This means getting plenty of exercise and good sleep, eating a healthy diet, keeping body weight down, avoiding diabetes, and taking the right nutritional supplements before you experience any signs of cognitive decline.

Researchers have identified a number of factors that may contribute to cognitive decline:

Diet. In one prospective study, more than 500 participants age 55 or older without clinical symptoms of dementia were evaluated. Their diets were assessed at the onset of the study, and participants were screened for symptoms of dementia an average of two years later. After adjusting for other factors, participants with the highest total fat intake were found to have a significantly elevated relative risk of dementia. An increased risk of dementia was also associated with a high dietary intake of saturated fat and cholesterol. On the other hand, a high intake of fish was associated with a significantly lower risk of dementia (Kalmijn V et al 1997). These findings have been supported in several other studies (Solfrizzi V et al 2005; Solfrizzi V et al 2003; Solfrizzi V et al 1999; Panza F et al 2004; Capurso A et al 2000).

Inflammation. The theory linking inflammation to cognitive decline is relatively new, but it appears to be consistent with our increasing understanding of the damage of chronic inflammation (as measured by C-reactive protein or interleukin-6 levels). Various studies have examined the association between inflammation and mild cognitive impairment and found compelling evidence. For example, one study of 2632 participants (mean age: 74 years) found that people who had both metabolic syndrome and high inflammation levels were more likely to experience cognitive impairment than were patients who suffered from neither. Metabolic syndrome is a cluster of abnormalities including high blood pressure, high insulin levels, obesity, and abnormal blood lipid levels. It is closely associated with increased risk of heart attack and stroke. In contrast, those with metabolic syndrome and low inflammation were not at increased risk of mild cognitive impairment (Yaffe K et al 1998).

Free radical damage. Free radicals are highly unstable molecules that react with other molecules in a damaging process known as oxidation. Areas of the body with high energy output, such as the brain, are particularly vulnerable to damage from free radicals. The body normally defends itself against the harmful effects of free radicals with antioxidants, including superoxide dismutase and glutathione peroxidase, as well as vitamins C and E. Animal studies have suggested that diets high in antioxidants can delay age-related memory loss (Joseph JA et al 1998; Perrig WJ et al 1997).

Vascular disease. Atherosclerosis that occurs in the arteries serving the brain (cerebrovascular disease) can reduce blood flow to the aging brain and increase the risk of stroke. The decreased blood flow can cause nerve cells in the brain to be lost prematurely. Consequently, mental function may decline. One study of 400 men (40 to 80 years old) found that vascular risk factors, such as excessive alcohol intake and elevated homocysteine levels, were associated with reduced processing capacity and speed of information processing (Aleman A et al 2005).

Stress. One interesting new theory about cognitive impairment associates it with stress. Studies have shown that older men with elevated levels of epinephrine (a stress hormone) are more likely to suffer from mild cognitive impairment than are their peers with normal levels (Karlamangla AS et al 2005). It has also been shown that everyday stresses combined with major stressful events may exert a cumulative effect over a lifetime that exacerbates cognitive decline (VonDras DD et al 2005).

Dehydroepiandrosterone deficiency. Dehydroepiandrosterone (DHEA) levels naturally decline as people age. Numerous studies have connected lowered DHEA levels to memory loss and decreased cognitive function (Racchi M et al 2001; Tan RS et al 2001).

Thyroid hormone. Hypothyroidism (low levels of thyroid hormone) is associated with poor concentration, memory disturbances, and depression. Low levels of thyroid hormone have also been linked to impaired cognitive function (Schindler AE 2003; Luboshitzky R et al 1996).

Tracking Mental Function

Screening for cognitive changes should be done even before overt changes in cognitive ability are apparent so that diet and lifestyle changes, as well as supplementation, can be started early.

The test most often used to evaluate memory and cognitive function is the Mini-Mental Status Examination, which tests multiple aspects of cognitive function, including orientation to time, place, and person; memory; verbal and mathematical abilities; judgment; and reasoning. In elderly patients, the clinician should differentiate early-stage dementia from normal age-associated memory impairment. People with memory impairment have a relative deficiency in recall compared with others their age. They also tend to learn new information more slowly, but if they are given extra time for such tasks, their intellectual performance is usually adequate.

Medical Treatment of Cognitive Decline

Age-related cognitive decline presents a clinical challenge, and there are no drugs approved by the FDA specifically for mild cognitive impairment. However, several drugs are regularly used in Europe for cognitive enhancement but are not approved for this use in the United States. The following drugs are commonly used to combat cognitive decline:

Piracetam. Piracetam has been shown to improve many cognitive activities, especially higher cortical functions. The evidence for piracetamís effectiveness comes from animal studies and from human studies in Alzheimerís disease and other organic brain disorders. It may enhance memory, particularly when used in combination with choline; increase attention and cognition; improve spatial learning; improve the brainís ability to utilize glucose; and improve circulation of blood in the brain (Bartus RT et al 1981; Pragina LL et al 1990; Senin U et al 1991; Gallai V et al 1991; Canonico PL et al 1991; Heiss WD et al 1988, 1991; Qian ZN et al 1992).

One study showed that after two months of oral treatment with piracetam in older human volunteers, single photon emission computed tomography imaging of the brain indicated a regional improvement in cerebral blood flow, particularly in the cerebellum (Dormehl IC et al 1999). It has also been shown to improve mild cognitive impairment and dementias among older study participants (Tariska P et al 2000).

Despite its extensive clinical use in Europe, piracetam has not been approved by the Food and Drug Administration (FDA) in the United States. For more information, visit www.piracetam.com.

Hydergine. Hydergine was discovered in the 1940s and later approved by the FDA to treat individuals over age 60 with signs or symptoms of mental incapacity. Unfortunately, when one study showed that hydergine was not effective in treating Alzheimerís disease, U.S. physicians virtually stopped prescribing it, even though the drug was never approved for the treatment of Alzheimerís disease. However, hydergine remains a popular prescription medication among health-conscious people seeking to slow age-related mental decline. Studies have revealed several mechanisms by which hydergine may protect against brain aging:
  • Increasing blood supply and oxygen to the brain (Emmenegger H et al 1968)
  • Enhancing metabolism in brain cells (Emmenegger H et al 1968)
  • Protecting the brain from damage during periods of decreased or insufficient oxygen supply (Boismare F et al 1978)
  • Slowing the deposit of age pigment (lipofuscin) in the brain (Amenta D et al 1988)
  • Preventing free radical damage to brain cells (Cahn J et al 1983)
  • Increasing intelligence, memory, learning, and recall (Ditch M et al 1971)
  • Enhancing the use of glucose by brain cells (Nagasawa H et al 1990)
  • Normalizing the brain levels of serotonin (Markstein R 1985)
  • Increasing superoxide dismutase and catalase in the brain while decreasing toxic levels of monoamine oxidase (MAO) (Sozmen EY et al 1998)
A review of existing studies found that hydergine might help prevent dementia (Olin J et al 2001). Although generally well tolerated, hydergine may induce mild nausea in approximately 5 percent of people.

L-deprenyl hydrochloride. MAO A and B are the primary enzymes that degrade neurotransmitters in the central nervous system and peripheral tissues. Elevated MAO levels may be associated with age-related neuronal deterioration. Elevated MAO levels are also associated with Parkinsonís disease. L-deprenyl hydrochloride (deprenyl), an MAO inhibitor, may be prescribed for Parkinsonís disease (Orru S et al 1999; Abell CW et al 2001).

Deprenyl has also been shown to induce rapid increases in nitric oxide production in blood vessels in the brain, which causes them to expand and increases blood flow to the brain. It was also shown to protect the endothelium from the toxic effects of amyloid beta-peptide, which is the main component of the plaques associated with Alzheimerís disease (Thomas T 2000). Another study showed that deprenyl protected cells from cell death caused by a neurotoxin, N-methyl(R)-salsolinol, and reactive oxygen species nitric oxide and peroxynitrite (Naoi M et al 2000).

Centrophenoxine. Centrophenoxine (meclofenoxate), a nootropic drug that enhances blood flow to the brain and acts as a free radical scavenger, is widely used in Europe in combination with piracetam to improve memory. Although centrophenoxine is readily available in Europe, it is not sold in the United States.

Researchers have proposed several mechanisms of action for centrophenoxine, including the following:
  • Increasing activity of free radical scavengers, especially in rat brain and heart tissues (al-Zuhair H et al 1998).
  • Providing antioxidant action (Zs-Nagy I 1989)
  • Increasing acetylcholinesterase activity in the brain of rats (Sharma D et al 1995)
  • Decreasing the deposition of the age-pigment lipofuscin, which has been shown to cause neuronal damage (Patro N et al 1992)
  • In animals, inhibiting total MAO, MAO-A, and MAO-B, which have been shown to damage brain cells (Stancheva SL et al 1988)
  • In animals, increasing the level of serotonin, a key neurotransmitter that can be depleted by elevated MAO levels (Stancheva SL et al 1988)
  • In animals, significantly increasing the fluidity of brain membranes, which can reverse the dehydration of nerve cells (Lustyik G et al 1985; Wood WG et al 1986)
Memory Drugs on the Horizon

One of the most promising memory-enhancing drugs is a group of compounds called ampakines, first developed by researchers at the University of California, Irvine. Ampakines work by enhancing communication among brain cells, which scientists believe gradually weaken or fail. A recent study in primates showed that ampakine (Ampakine CX717) improved cognitive performance and reversed the deleterious effects of sleep deprivation (Porrino LJ et al 2005).

At the University of Vermont, scientists are studying the connection between loss of nicotinic receptors on the one hand and cognitive impairment and Alzheimerís disease on the other. These receptors, located on the surface of neuron cells in the brain, modulate neuronal transmission. They bind acetylcholine and nicotine. Scientists have shown that nicotinic receptors appear to be important in regulating learning and memory, anxiety, and motor performance. Stimulation of these receptors with nicotine or novel nicotinic agonists improves certain aspects of attention and memory functioning in normal individuals as well as in patients with Alzheimerís disease, attention deficit/hyperactivity disorder, and schizophrenia. The group is now recruiting patients with amnesiac mild cognitive impairment for a six-month trial of transdermal nicotine to demonstrate cognitive symptom relief.

Natural Hormone Replacement

Fortunately, there are a number of strategies people can use to slow age-related memory loss and cognitive decline. Chief among them is bioidentical hormone replacement. As we age, levels of virtually all hormones decline. Ideally, hormone replacement with bioidentical hormones seeks to restore hormone levels to those of a healthy person in his or her mid-20s.

Testosterone. Testosterone may provide a protective mechanism against age-related mental decline as well as Alzheimerís disease. Researchers in England found that lower levels of testosterone were present in men with Alzheimerís disease than in controls (Hogervorst E et al 2001). It appears that normal testosterone levels protect brain cells from a toxic peptide called beta-amyloid, which tends to accumulate in certain regions of an aging brain. Beta-amyloid has been implicated in the development of Alzheimerís disease. One study observed the effects on cultured neurons exposed to beta-amyloid in the presence of testosterone. The resulting toxicity from beta-amyloid was significantly reduced by testosterone (Pike CJ 2001). Other researchers have found that testosterone supplementation in elderly men may be beneficial in preventing beta-amyloid buildup in the brain and possibly in treating Alzheimerís disease (Goodenough S et al 2000; Gouras GK et al 2000).

Several effects of low testosterone have been reported. These effects include a decreased ability to concentrate, moodiness and emotionality, reduced intellectual agility, feelings of weakness, passive attitudes, and reduced interest in surroundings (Wright AS et al 1999). A consistent finding in the scientific literature is that testosterone replacement therapy produces an increased feeling of well-being, just as low testosterone levels correlate with symptoms of depression and other psychological disorders (Moger WH 1980; Barrett-Connor E et al 1999; Rabkin JG et al 1999; Schweiger U et al 1999; Seidman SN et al 1999).

Testosterone supplementation should be carried out only under the supervision of a qualified physician and after comprehensive blood testing. Some cancers are hormone dependent, and the growth of certain hormone-dependent cancers may be increased by testosterone therapy.

Melatonin. Melatonin, a pineal hormone that regulates the bodyís circadian rhythm, should also be considered. Decreased levels of melatonin may result in poor sleep quality, decreased immune system function, and reduced scavenging of free radicals (Karasek M 2004).

Pregnenolone. Pregnenolone is a neurosteroid hormone that is produced from cholesterol and that has been shown to have a direct influence on brain function. In animal studies, pregnenolone was found to boost levels of the vital neurotransmitter acetylcholine, which is deficient in animal models of Alzheimerís disease and cognitive decline. In the same study, it also boosted the animalsí ability to sleep, which is connected to memory (Mayo W et al 2001). Other animal studies have demonstrated that pregnenolone levels decline in Alzheimerís patients and that this hormone has a neuroprotective effect (Weill-Engerer S et al 2002).

DHEA. DHEA levels have been shown to decline significantly with advanced age (Ferrari E et al 2001; Ferrari E et al 2004). One of the effects of DHEA replacement therapy is an enhanced sense of general well-being. This effect was found at doses of 50 mg and 100 mg daily (Yen S et al 1995). Very few adverse side effects have been reported with DHEA, although in women, androgenic side effects such as facial hair growth and acne can occur with doses as low as 50 mg (Casson P et al 1995). Life Extension suggests periodic, systematic blood testing to assess an individualís response to DHEA dosing.

Thyroid hormone. Hypothyroidism is a well-known and relatively common cause of reversible dementia and the most treatable cause of cognitive decline in the older population. A recent study indicates that even subclinical hypothyroidism may be a predisposing factor for depression, cognitive impairment, and dementia (Davis JD et al 2003).

Thyroid hormone blood tests can help detect suboptimal hormone levels and confirm the diagnosis of hypothyroidism. Thyroid peroxidase antibodies should be measured in all patients with subclinical hypothyroidism because these patients are at greatest risk of progressing to overt hypothyroidism (Beers MH et al 1999). Several thyroid hormone preparations are available, including synthetic preparations of L-thyroxine (T4), triiodothyronine (T3), combinations of the two synthetic hormones, and desiccated animal thyroid.

Most physicians specializing in antiaging recommend a combination of T4 and T3 rather than T4 alone in treating hypothyroidism or subclinical hypothyroidism. Furthermore, thyroid function should be evaluated by measuring thyroid-stimulating hormone, T4, and free T3 levels. Since T3 is the most metabolically active form of thyroid hormone and mediates effects at the cellular level, physicians should consider restoring thyroid hormone in patients with clinical symptoms consistent with low thyroid hormone and restoring normal thyroid-stimulating hormone levels if T4 and T3 levels are low. Physicians specializing in antiaging should also consider prescribing T3 if thyroid-stimulating hormone and T4 levels are normal but T3 levels are low and the patient manifests signs and symptoms consistent with hypothyroidism.

Continued . . .


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