Life Extension Foundation
All aging humans will develop some degree of decline in cognitive capacity as time progresses. Data indicates that deterioration of the biological framework that underlies the ability to think and reason begins as early as the mid twenties and includes a drop in regional brain volume, loss of myelin integrity, cortical thinning, impaired serotonin, acetylcholine, and dopamine receptor binding and signaling, accumulation of neurofibrillary tangles, and altered concentrations of various brain metabolites. Cumulatively, these changes give rise to a variety of symptoms associated with aging, such as forgetfulness, decreased ability to maintain focus, and decreased problem solving capability. If left unchecked, symptoms oftentimes progress into more serious conditions, such as dementia and depression, or even Alzheimer’s disease.
Cognitive decline does not affect all individuals equally; clear associations exist between the rate and severity of cognitive decline and a variety of factors, including oxidative stress and free radical damage, chronic low-level inflammation, declining hormone levels, endothelial dysfunction, excess body weight, suboptimal nutrition, lifestyle, social network, other medical conditions, and various biomarkers. Fortunately, many of these factors are modifiable to a significant extent, and proactive lifestyle changes, cognitive training, and nutritional interventions have been shown to decrease the rate of intellectual decay and potentially reverse age-related cognitive decline.
The Aging Brain
The aging process profoundly impacts the brain in ways that can be observed on multiple levels, ranging from sub-cellularly to macro-structurally. On a diminutive scale, aging causes deterioration of neuronal and mitochondrial membranes, which leads to the loss of cellular integrity and impaired neuronal function. The physical structure of the brain as a whole also deteriorates with age. Even in healthy individuals, aging accounts for volume variances of 37% in the thalamus, which is involved in sight, hearing, and the sleep-wake cycle; 36% in the nucleus accumbens, which plays a major role in mood regulation (e.g. pleasure, fear, reward); and 33% in the hippocampus, a critical site for consolidation of short-term to long-term memory. Taken together, age related neuroanatomical changes account for an estimated 25% to 100% of the variance in cognitive ability between young and aged individuals. In other words, age related cognitive decline occurs in tandem with the physical degradation of brain structure. Thus, conserving cognitive vigilance into late life requires early and aggressive intervention to preserve the brain in its youthful physical and functional state.
Biological Risk Factors Contributing to Cognitive Decline
Various biological systems work in conjunction to maintain optimal brain function and cognitive ability. Perturbations in the harmony of these systems, caused by such age-associated insults as chronic inflammation oxidative stress, insulin resistance, declining hormone levels, and endothelial dysfunction, result in physical deterioration of the brain and subsequent cognitive decline.
Oxidative Stress. The brain is particularly susceptible to oxidative damage since it consumes roughly 20% of the oxygen used by the entire body, and because it contains high concentrations of phospholipids, which are especially prone to oxidative damage in the context of high metabolic rate. As we age, there is a significant and progressive increase in the level of oxidatively damaged DNA and lipids in the brain; this is true even for healthy individuals. Over time, this free radical damage leads to the death of neurons.Numerous studies have implicated oxidative stress in the pathology of mild cognitive impairment and Alzheimer’s disease alike.
Hormonal Imbalance.
Distributed throughout the brain are steroid hormone receptors which function to regulate the transcription of a vast array of genes involved in cognition and behavior. Adequate steroid hormone receptor activation in the brain is a fundamental determinant in many aspects of our lives that we take for granted. When hormonal imbalances or deficiencies disrupt receptor activation, cognitive deficits and emotional turmoil are the result.
Dehydroepiandrosterone (DHEA)
Age-associated decline in levels of the adrenal hormone dehydroepiandrosterone (DHEA), which is very active in the central nervous system, are also tied to worsening cognitive performance. In a study involving over 750 aging subjects, Mini-Mental State Examination (MMSE) scores were significantly associated with levels of DHEA-s, the sulfated metabolic derivate of DHEA, which is more highly concentrated in humans. Moreover, those individuals with the lowest levels of DHEA-s at baseline displayed greater cognitive decline over time than those with higher initial levels. In a separate community-based study involving nearly 300 healthy women, levels of DHEA-S correlated positively with superior executive function, concentration, and working memory. Accordingly, in a double-blind, placebo controlled clinical trial, six-months of supplementation with 25 mg of DHEA daily improved measures of cognitive function, especially verbal fluency, in aging women.
Thyroid hormones
During the developmental period thyroid hormones play a critical role in ensuring proper growth and maturation of the brain.91 Thyroid hormone levels may also be related to cognitive function in adults, though the evidence in this area is inconsistent. However, limited associations with both hypo- (low) and hyper- (high) thyroid function and cognitive impairment exist in the peer reviewed literature, thus maintaining levels of TSH, T3, and T4 within normal ranges is suggested.
Hypertension
Small, delicate capillaries, like those that perpetuate the flow of blood throughout the brain, are particularly susceptible to damage caused by elevated blood pressure. Chronic hypertension leads to the breakdown of cerebrocapillaries, a condition associated with the development neurodegenerative diseases and cognitive impairment.Evidence suggests that blood pressure of 115/75 mmHg significantly reduces the risk for cardiovascular disease,107 and thus may be an ideal target for those who wish to maintain optimal cognitive performance as well.
Diabetes and Insulin Resistance.
Due to the high metabolic demand for energy in the brain, even small perturbations in glucose metabolism can noticeably impact cognitive performance. Diabetes (hyperglycemia) has been linked with lower levels of neuronal growth factors, decreased brain volume, and higher incidence of all types of dementia.
Obesity.
Adipose tissue secretes molecules that directly influence multiple functions within the brain. There is a clearly established reciprocal relationship between adiposity (amount of body fat) and overall brain volume and cognitive function. In other words, as bodyweight increases, brain volume drops and cognitive function worsens.