User:Psyc4600/Group15

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As you age, you can expect gradual changes to occur at your body’s own pace. Although each individual is different, general trends of deterioration in many cognitive functions exist. There are various structural, chemical and genetic changes that occur in old age. Some changes in the ability to think are considered a normal part of the aging process. Abilities such as encoding new memories of episodes and facts, working memory, and processing speed are relatively impaired and tend to decline in old age. [1]. However, short-term memory, autobiographical memory, semantic knowledge and emotional processing remain relatively stable [1].

Structural Changes[edit]

Age and change seemingly go hand in hand. As one ages, there are a number of changes that take place, whether physical, chemical or biological. Therefore, it is logical to assume the brain is no exception to this phenomenon. Computed Tomography (CT) studies have found that the cerebral ventricles expand as a function of age, and this process is known as ventriculomegaly. Similarly, this pattern of increasing in size has been seen with the cerebral sulci [2]. In contrast to these age-related associations, recent in vivo MRI volumetry studies have reported age-related decreases in cerebral volume [2]. The brain is very complex, and is comprised of many different areas and types of tissue, or matter. Having said that, differing properties of different tissues in the brain may be more or less susceptible to age-induced changes [2]. The brain matter can be classified as either grey matter, or white matter. Grey matter consists of cell bodies in the cortex and subcortical nuclei, whereas white matter is comprised of tightly packed myelinated axons connecting the neurons of the cerebral cortex to each other and with the periphery [2].

Memory Loss[edit]

There have been many different types of memory identified in humans, such as episodic, semantic, strategic, working, source spatial, and non-declarative [2]. Studies done by Rapp et al, have found that memory functions, more specifically those associated with the medial temporal lobe are especially vulnerable to age-related decline [3]. A number of studies utilizing a variety of methods such as histological, structural imaging, functional imaging, and receptor binding have converging evidence that the frontal lobes and frontal-striatal dopaminergic pathways are especially affected by age-related processes resulting in memory [2].

Loss of Neural Circuits and Brain Plasticity[edit]

Brain plasticity refers to the brains ability to change structure and function [4]. This ties in to that old phrase “if you don’t use it, you lose it”, which is another way of saying, if you don’t use it, your brain will devote less somatotopic space for it. One proposed mechanism for the observed age-related plasticity deficits in animals is the result age-induced alterations in calcium regulation [5] The changes in our abilities to handle calcium will ultimately influence neuronal firing and the ability to propagate action potentials, which in turn would affect the ability of the brain to alter its structure or function (i.e. its plastic nature). Due to the complexity of the brain, with all of its structures and functions, it is logical to assume that some areas would be more vulnerable to aging than others. Two circuits worth mentioning here are the hippocampal and neocortical circuits [3]. It has been suggested that age-related cognitive decline is due in part not to neuronal death, but in fact, synaptic alterations. Evidence in support of this idea from animal work has also suggested that this cognitive deficit is due to functional and biochemical changes such as enzymatic activity, chemical messengers or gene expression, in cortical circuits [3].

Thinning of the Cortex[edit]

Advances in MRI technology have provided the ability to see the brain structure in great detail in an easy, non-invasive manor in vivo [6]. Bartzokis et al, has noted that there is a decrease in grey matter volume between adulthood an old age. Whereas, white matter volume was found to increase from age 19-40, and decline after this age [6]. Experiments using Voxel-based morphometry have identified areas such as the insula and superior parietal gyri as being especially vulnerable to age-related losses in grey matter of older adults [6]. Sowell et al, reported that the first 6 decades of an individuals’ life were correlated with the most rapid decreases in grey matter density, and this occurred over dorsal frontal, and parietal lobes on both interhemispheric and lateral brain surfaces. Also worth noting, that areas such as the cingulate gyrus, and occipital cortex surrounding the calcarine sulcus appear exempt from this decrease in grey matter density over time [6]. Age effects on grey matter density in the posterior temporal cortex appear more predominantly in the left versus right hemisphere, and were confined to posterior language cortices. Certain language functions such as word retrieval and production were found to be located to more anterior language cortices, and deteriorate as a function of age. Sowell et al, also reported that these anterior language cortices were found to mature and decline earlier than the more posterior language cortices [6].

Age-Related Neuronal Morphology[edit]

There is converging evidence from cognitive neuroscientists around the world that age-induced cognitive deficits are not due to neuronal loss or cell death, but is a result of small region-specific morphology of neurons [5]. Studies by Duan et al, have shown that dendritic arbors and dendritic spines of cortical pyramidal neurons decrease in size and/or number in specific regions and layers of human and non-human primate cortex as a result of age (Duan et al, 2003; morph). Interestingly, a 46% decrease in spine number and spine density has been reported in humans older than 50 compared with younger individuals [3]. An electron microscopy study in monkeys reported a 50% loss in spines on the apical dendritic tufts of pyramidal cells in prefrontal cortex of old animals (27–32 years old) compared with young ones (6–9 years old) [3].

Chemical Changes[edit]

In addition to the structural changes that the brain incurs with age, the aging process also entails a broad range of biochemical changes.

Changes in Chemical Messengers[edit]

Neurons communicate with each other via specialized chemical messengers called neurotransmitters. Several studies have identified a number of these neurotransmitters, as well as their receptors, that exhibit a marked alteration in different regions of the brain as part of the the normal aging process.

Dopamine[edit]

An overwhelming number of studies have reported age-related changes in dopamine synthesis, binding sites, and number of receptors. Studies using positron emission tomography (PET) in living human subjects have shown a significant age-related decline in dopamine synthesis[7], notably in the striatum and extrastriatal regions (excluding the midbrain)[8]. Significant age-related decreases in dopamine receptors D1, D2, and D3 have also been highly reported[9][10][11][12][13]. A general decrease in D1 and D2 receptors has been shown[11], and more specifically a decrease of D1 and D2 receptor binding in the caudate nucleus and putamen[13][10]. A general decrease in D1 receptor density has also been shown to occur with age. Significant age-related declines in dopamine receptors, D2 and D3 were detected in the anterior cingulate cortex, frontal cortex, lateral temporal cortex, hippocampus, medial temporal cortex, amygdala, medial thalamus, and lateral thalamus[9] One study also indicated a significant inverse correlation between dopamine binding in the occipital cortex and age[10]. Postmortem studies as well show that the number of D1 and D2 receptors decline with age in both the caudate nucleus and the putamen, although the ratio of these receptors did not show age-related changes[12]. The loss of dopamine with age is thought to be responsible for many neurological symptoms that increase in frequency with age, such as decreased arm swing and increased Rigidity (neurology)[14]. Changes in dopamine levels may also cause age-related changes in cognitive flexibility[14].

Serotonin[edit]

Decreasing levels of different serotonin receptors and the serotonin transporter, 5-HTT, have also been shown to occur with age. Studies conducted using PET methods on humans, in vivo, show that levels of the S2 receptor in the caudate nucleus, putamen, and frontal cerebral cortex, decline with age[13]. A decreased binding capacity of the 5-HT2 receptor in the frontal cortex was also found[11], as well as a decreased binding capacity of the serotonin transporter, 5-HHT, in the thalamus and the midbrain[15]. Postmortem studies on humans have indicated decreased binding capacities of serotonin and a decrease in the number of S1 receptors in the frontal cortex and hippocampus as well as a decrease in affinity in the putamen[16].

Glutamate[edit]

Glutamate is another neurotransmitter that shows a trend to decrease with age[17][18][19]. Studies have shown older subjects to have lower glutamate concentration in the motor cortex compared to younger subjects[19]A significant age-related decline especially in the parietal gray matter, basal ganglia, and to a lesser degree, the frontal white matter, has also been noted.[17][18]Although these levels were studied in the normal human brain, the parietal and basal ganglia regions are often affected in degenerating brian diseases associated with aging and it has therefore been suggested that brain glutamate may be useful as a marker of brain diseases that are affected by aging.[17].

Genetic Changes[edit]

Variation in the effects of cognitive aging in different individuals is attributable to both genetic and environmental factors. As in so many other science disciplines, the nature versus nurture debate is an ongoing conflict in the field of cognitive neuroscience. These factors relate to preferred strategies employed by individuals, as well as their susceptibility to neuropathology [1] and help determine whether a person ages gracefully or develops dementia [20].

The dexterity of aging is a spectrum between normal cognitive aging and outright clinical dementia. The search for genetic factors has always been an important aspect in trying to understand neuro-pathological diseases. In general, cognitive aging is related to an increased trend of developing both Alzheimer’s Disease (AD) and vascular pathologies [21]. Understanding the genetic component in developing AD has contributed greatly to the understanding the genetics behind normal or “non-pathological” aging [20].

The ability of an individual to endure this progressive pathology without demonstrating clinical cognitive symptoms is called cognitive reserve [22]. This hypothesis comes into play when two patients have the same brain pathology, one leading to noticeable clinical symptoms, while the other continues to function relatively normally. Cognitive reserve explores the specific differences between these two individuals, biologically, genetically and environmentally which makes one more susceptible to an increased decline in cognitive functioning, and allows the other to age more gracefully.

Environmental Influences[edit]

The anonymous division between genetic and environmental factors has been explored using twin studies. It’s unknown how much credit should be given to either genetics or environmental influences, but it is known that both play a significant part in cognitive aging and both areas should be studied thoroughly. Research by Anderton has clearly shown one important environmental power as being an individual’s level of education [20]. It has been made known that poor educational achievement quickens memory decline and increases the likelihood of dementia [20]. Not only this, research has shown that individuals with high levels of education, intellectual ability and social economic status are in general, more likely to engage in lifestyles that promote graceful cognitive aging [22].

Neurofibrillary Tangles[edit]

Age-related neuro-pathologies such as Alzheimer’s disease, Parkinson’s disease, diabetes, hypertension and arteriosclerosis make it difficult to distinguish the normal patterns of aging [1]. One of the important comparison aspects between normal aging and pathological aging are neurofibrillary tangles. Neurofibrillary tangles are composed of paired helical filaments (PHF) [20]. In normal, non-demented aging, the number of tangles in each affected cell body is relatively low [20] and restricted to the olfactory nucleus, parahippocampal gyrus, amygdala and entorhinal cortex [23]. As the non-demented individual ages, there is a general increase in the density of tangles, but no significant difference in WHERE tangles are found [23]. The other main neurodegenerative contributor commonly found in the brain of patients with AD is amyloid plaques. However, unlike tangles, plaques have not been found to be a consistent feature of normal aging [23].

Role of Oxidative Stress[edit]

Cognitive impairments has been attributed to oxidative stress, inflammatory reactions and changes in the cerebral microvasculature [21]. The exact intensity of each of these mechanisms in affecting cognitive aging is unknown. Oxidative stress is the most controllable risk factor and is the best understood. The online Merriam-Webster Medical Dictionary defines oxidative stress as, "physiological stress on the body that is caused by the cumulative damage done by free radicals inadequately neutralized by antioxidants and that is to be associated with aging." [24] Hence, simply put, oxidative stress is the damage done to the cells by free radicals that have been released from the oxidation process.

Compared to other tissues in the body, the brain is deemed abnormally sensitive to oxidative damage. [25]. Increased oxidative damage has been associated with neurodegenerative diseases, mild cognitive impairment and individual differences in cognition in healthy elderly people. In ‘normal aging’, the brain is undergoing oxidative stress in a multitude of ways. The main contributors include, protein oxidation, lipid peroxidation and oxidative modifications in nuclear and mitochondrial DNA [25]. Oxidative stress can damage DNA replication and inhibit repair through many complex processes. One of these processes includes telomere shortening in DNA components [26]. Each time a somatic cell replicates, the telomeric DNA component shortens. As telomere length is partly inheritable [26] , there is individual difference in the age of an individual and the onset of cognitive decline.

Delaying the Effects of Aging[edit]

The process of aging is inevitable, however, one may potentially delay the effects and severity of this progression. Some of the things that may be done to delay cognitive decline as one ages are;

  • Stay intellectually engaged i.e. Stay socially active, read newspapers and mental activities (such as crossword puzzles)
  • Exercise
  • Minimize the stressful events in your life
  • Maintain a healthy diet i.e. Omega-3 fatty acids, and protective antioxidants [1]

References[edit]

  1. ^ a b c d e Gabrieli, J. & Hedden, T. (2004). Insights into the ageing mind: a view from cognitive neuroscience. Nature Reviews, 5; 87-96
  2. ^ a b c d e f Craik, F. & Salthouse, T.(2000) The Handbook of Aging and Cognition, 2nd Edition. United States of America, Lawrence Erlbaum Associates, Inc
  3. ^ a b c d e Hof, P. & Morrison, J. (2004). The aging brain: morphomolecular senescence of cortical circuits. Trends in Neuroscience, 27(10); 607-613
  4. ^ Kolb, B. & Whishaw, I. (1988). Brain plasticity and behaviour. Annual Review of Psychology, 49; 43-64
  5. ^ a b Barnes, C. & Burke, S. (2006). Neural plasticity in the ageing brain. Nature Publishing Group, 7; 30-40
  6. ^ a b c d e Henkenius, A., Peterson, B., et al. (2003). Mapping cortical change across the human life span. Nature Neuroscience, 6(3); 309-315.
  7. ^ Hof, P. R., & Mobbs, C. V. (2009). Handbook of the neuroscience of aging. London, UK: Elsevier Inc.
  8. ^ Ota, M., Yasuno, F., Ito, H., Seki, C., Kozaki, S., Asada, T., & Suhara, T. (2006). Age-related decline of dopamine synthesis in the living human brain measured by positron emission tomography with L-[β- 11 C]DOPA. Life Sciences. 79; 730-736.
  9. ^ a b Kaasinen, V., Vilkman, H., Hietala, J., Någren, K., Helenius, H., Olsson, H., Farde, L., & Rinne, J.O. (2000). Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain. Neurobiology of Aging. 21; 683– 688.
  10. ^ a b c Wang, Y., Chan, G.L.Y., Holden, J.E., Dobko, T., Mak, E., Schulzer, M., Huser, J.M., Snow, B.J., & Ruth, T.J. (1998). Age-Dependent Decline of Dopamine D1 Receptors in Human Brain: A PET Study. Science. 30; 56-61.
  11. ^ a b c Iyo, M., & Yamasaki, T. (1993). The detection of age-related decrease of dopamine, D1, D2 and serotonin 5-HT2 receptors in living human brain. Prog. Neuro-Psycopharmacol & Biol. Psychait. 17; 415-421.
  12. ^ a b Juha O. Rinne, Pirkko Lonnberg and Paivi Marjamaiki (1989). Age-dependent decline in human brain dopamine D1 and D2 receptors. Brain Research. 508; 349-352.
  13. ^ a b c Wong, D.F., Wanger, H.N., Dannals, R.F., Links, J.M., Frost, J.J., Ravery, H.T., Wilson, A.A., Rosenbaum, A.E., Gjedde, A., Douglass, K.H., Petronis, J.D., Folstein, M.F., Toung, J.K.T., Burns, H.D., Kuhnar, M.J. (1984). Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science. 266; 1393-1396.
  14. ^ a b Wang, E., & Snyder, S. D. (1998). Handbook of the aging brain. San Diego, California: Academic Press.
  15. ^ Yamamoto, M., Suhara, T., Okubo, Y., Ichimiya, T., Sudo, Y., Inoue, Y., Takano, A., Yasuno, F., Yoshikawa, K., & Tanada, S. (2001). Age-related decline of serotonin transporters in living human brain of healthy males . Life Sciences. 71; 751-757.
  16. ^ Marcusson, J., Oreland, L., & Winblad, B. (1984). Effect of age on human brain serotonin (S-1) binding sites. Journal of Neurochemistry. 43; 1699-1705.
  17. ^ a b c Chang, L., Jiang, C.S., & Ernst, T. (2009). Effects of age and sex on brain glutamate and other metabolites. Magnetic Resonance Imaging. 27; 142-145.
  18. ^ a b Saliasuta, N., Chang, L., & Ernst, T. (2008). Regional variations and the effects of age and sex on brain glutamate and other metabolites. Magnetic Resonance Imaging. 26; 667-675.
  19. ^ a b Kaiser, L.G., Schuff, N., Cashdollar, N., Weiner, M.W. (2005). Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T. Neurobiology of aging. 26; 665-672.
  20. ^ a b c d e f Anderton, B. (2002). Ageing of the brain. Mechanisms of Ageing and Development. 123; 811-817
  21. ^ a b Appleton, C., Deary, I., et al. (2004). Cognitive reserve and the neurobiology of cognitive ageing. Ageing Research Reviews. 3; 369-382
  22. ^ a b Scarmeas, N. & Stern, Y. (2003). Cognitive reserve and lifestyle. Journal of Clinical and Experimental Neuropsychology, 25(5); 625-633
  23. ^ a b c Davis, P., Morris, J., et al. (1991). The distribution of tangles, plaques, and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiology of Aging, 12; 295-312
  24. ^ Oxidative Stress. (n.d.) In Merriam-Webster Dictionary online. Retrieved from http://www.merriam-webster.com/medical/oxidative stress
  25. ^ a b Butterfield, A., Ding, Q., et al. (2005). Evidence of increase oxidative damage in subjects with mild cognitive impairment. Neurology; 64; 1152-1156
  26. ^ a b Deary, I., Harris, S., et al. (2006). The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people. Neuroscience Letters, 406; 260-264.
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