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Chapter 15 - Mechanisms of Aging-Related Cognitive Decline

Published online by Cambridge University Press:  30 November 2019

Kenneth M. Heilman
Affiliation:
University of Florida
Stephen E. Nadeau
Affiliation:
University of Florida
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Summary

Unlike the degenerative disorders that cause dementias, which stem from a modest number of aberrant processes, aging-related cognitive changes reflect a host of mechanisms. These include mechanisms associated with a person’s condition, e.g., drugs, pain, depression, and sleep disorders. They include mechanistic changes linked to the aging process, e.g., enhanced neural network noise, increased neighborhood density, age of acquisition effects, degraded selective engagement of neural networks, alteration of the balance between volitional and reactive intention and attention, declines in neurotransmitter function, and brain ontogenesis over the life span. They include changes best characterized as senescent physiology and best demonstrated in decline in functions essential to episodic memory formation related to impaired encoding in the hippocampal cornu amonis (CA) fields and slowed neurogenesis in the hippocampal dentate gyrus. Finally, they include processes best characterized as senescent pathology, the best understood being degradation of myelin and associated reduction of central conduction velocities and slowing of processing speed. No longer should cognitive changes associated with aging be viewed as a simple manifestation of a unitary aging process. The large number of mechanisms at play and their complexity offer many opportunities for therapeutic intervention.

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Publisher: Cambridge University Press
Print publication year: 2019

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References

Nelson, PT, Trojanowski, JQ, Abner, EL, Al-Janabi, OM, Jicha, GA, Schmitt, FA, et al. “New old pathologies”: AD, PART, and cerebral age-related TDP-43 with sclerosis [CARTS]. Journal of Neuropathology and Experimental Neurology. 2016;75:482–98.CrossRefGoogle ScholarPubMed
Neltner, JH, Abner, EL, Jicha, GA, Schmitt, FA, Patel, E, Poon, LW, et al. Brain pathologies in extreme old age. Neurobiology of Aging. 2016;37:111.Google Scholar
Kryscio, RJ, Abner, EL, Nelson, PT, Benbnett, D, Schneider, Js, Yu, L, et al. The effect of vascular neuropathology on late-life cognition: results from the SMART Project. Journal of Prevention of Alzheimer’s Disease. 2016;3:8591.Google Scholar
Lodato, MA, Rodin, RE, Bohrson, CL, Coulter, ME, Barton, AR, Kwon, M, et al. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science. 2018;359:555–9.Google Scholar
Chancellor, MB, Staskin, DR, Kay, GG, Sandage, BW, Oefelein, MG, Tsao, JW. Blood–brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder. Drugs Aging. 2012;29:259–73.Google Scholar
Richardson, K, Fox, C, Maidment, I, Steel, N, Loke, YK, Arthur, A, et al. Anticholinergic drugs and risk of dementia: a case-control study. British Medical Journal. 2018;360:k1315.Google Scholar
Nadeau, SE, Bowers, D, Jones, TL, Wu, SS, Triggs, WJ, Heilman, KM. Cognitive effects of treatment of depression with repetitive transcranial magnetic stimulation. Cognitive and Behavioral Neurology. 2014;27:7787.Google Scholar
Langer, N, Hänggi, J, Müller, NA, Simmen, HP, Jäncke, L. Effects of limb immobilization on brain plasticity. Neurology. 2012;78:182–8.Google Scholar
Maguire, EA, Woollett, K, Spiers, HJ. London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis. Hippocampus. 2006;16:1091–101.Google Scholar
Jenkins, WM, Merzenich, MM, Recanzone, G. Neocortical representational dynamics in adult primates: implications for neuropsychology. Neuropsychologia. 1990;28:573–84.Google Scholar
Henley, JM, Wilkinson, KA. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging. Dialogues in the Clinical Neurosciences. 2013;15:1127.Google Scholar
Vasic, N, Wolf, ND, Sosic-Vasic, Z, Connemann, BJ, Sambataro, F, von Strombeck, A, et al. Baseline brain perfusion and brain structure in patients with major depression: a multimodal magnetic resonance imaging study. Journal of Psychiatry and Neuroscience. 2015;40:412–21.Google Scholar
Goodkind, M, Eickhoff, SB, Oathes, DJ, Jiang, Y, Chang, A, Jones-Hagata, LB, et al. Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry. 2015;72:305–15.Google Scholar
Mitchell, AJ, Vaze, A, Rao, S. Clinical diagnosis of depression in primary care: a meta-analysis. Lancet. 2009;374:609–19.Google ScholarPubMed
Mander, BA, Winer, JR, Walker, MP. Sleep and human aging. Neuron. 2017;94:1936.Google Scholar
Leger, D, Debellemaniere, E, Rabat, A, Bayon, V, Benchenane, K, Chennaoui, M. Slow-wave sleep: from the cell to the clinic. Sleep Medicine Reviews. 2018.Google Scholar
Alvarez, P, Squire, LR. Memory consolidation and the medial temporal lobe: a simple network model. Proceedings of the National Academy of Sciences. 1994;91:7041–5.CrossRefGoogle ScholarPubMed
McClelland, JL, McNaughton, BL, O’Reilly, RC. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psych Rev. 1995;102:419–57.CrossRefGoogle ScholarPubMed
Rolls, ET. Cerebral Cortex: Principles of Operation. Oxford: Oxford University Press; 2016.Google Scholar
Squire, LR, Zola-Morgan, S. The medial temporal lobe memory system. Science. 1991;253:1380–6.Google Scholar
Tononi, G, Cirelli, C. Sleep and the price of plasticity; from synaptic and cellular homeostasis to memory consolidation and integration. Neuron. 2014;81:1234.Google Scholar
Allen, RP, Walters, AS, Montplaisir, J, Hening, W, Myers, A, Bell, TJ, et al. Restless legs syndrome prevalence and impact. Archives of Internal Medicine. 2005;165:1286–92.Google Scholar
Lin, CM, Davidson, TM, Ancoli-Israel, S. Gender differences in obstructive sleep apnea and treatment implications. Sleep Med Rev. 2008;12:481–96.Google Scholar
Voytek, B, Kramer, MA, Case, J, Lepage, KQ, Tempesta, ZR, Knight, RT, et al. Age-related changes in 1/f neural electrophysiological noise. Journal of Neuroscience. 2015;23:13257–65.Google Scholar
Yerkes, RM, Dodson, JD. The relation of strength of stimulus to rapidity of habit formation. Journal of Comparative Neurology and Psychology. 1908;18:459–82.Google Scholar
Devilbiss, DM, Waterhouse, BD. Norepinephrine exhibits two distinct profiles of action on sensory cortical neuron responses to excitatory synaptic stimuli. Synapse. 2004;37:273–82.Google Scholar
Devilbiss, DM, Berridge, CW. Cognition-enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness. Biological Psychiatry. 2008;64:626–35.CrossRefGoogle ScholarPubMed
Durstewitz, D, Seamans, J. The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia. Biological Psychiatry. 2008;64:739–49.Google Scholar
Cools, R, D’Esposito, M. Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biological Psychiatry. 2011;2011:e113e125.CrossRefGoogle Scholar
Conley, P, Burgess, C. Age effects on a computational model of memory. Brain and Cognition. 2000;43:104–8.Google ScholarPubMed
Nadeau, SE. Attractor basins: a neural basis for the conformation of knowledge. In: Chatterjee, A, Coslett, HB, editors. The Roots of Cognitive Neuroscience. Oxford: Oxford University Press; 2014, pp. 305–33.Google Scholar
Dumutriu, D, Hao, J, Hara, Y, Kaufmann, J, Janssen, WGM, Lou, W, et al. Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-relating cognitive impairment. Journal of Neuroscience. 2010;30:7507–15.Google Scholar
Nadeau, SE, Crosson, B. Subcortical aphasia. Brain and Language. 1997;58:355402, 436–58.Google Scholar
Desimone, R, Duncan, D. Neural mechanisms of selective visual attention. Annual Reviews of Neuroscience. 1995;18:193222.Google Scholar
Moran, J, Desimone, R. Selective attention gates visual processing in extrastriate cortex. Science. 1985;229:782–4.CrossRefGoogle ScholarPubMed
Rolls, ET, Deco, G. Stochastic cortical neurodynamics underlying the memory and cognitive changes in aging. Neurobiology of Learning and Memory. 2015;118:150–61.CrossRefGoogle ScholarPubMed
Nadeau, SE, Heilman, KM. Frontal mysteries revealed. Neurology. 2007;68:1450–3.Google Scholar
Chavis, DA, Pandya, DN. Further observations on corticofrontal connections in the rhesus monkey. Brain Research. 1976;117:369–86.Google Scholar
Goldman-Rakic, PS. Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. Prog Brain Res. 1990;85:325–36.Google Scholar
Ongür, D, Price, JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cerebral Cortex. 2000;10:206–19.Google Scholar
Kumar, A. NMDA receptor function during senescence: implication on cognitive performance. Front Neurosci. 2015;9:473.CrossRefGoogle ScholarPubMed
Onur, OA, Schlaepfer, TE, Kukolja, J, Bauer, A, Jeung, H, Patin, A, et al. The N-methyl-D aspartate receptor co-agonist d-cycloserine facilitates declarative learning and hippocampal activity in humans. Biological Psychiatry. 2010;67:1205–11.Google Scholar
Feld, GB, Lange, T, Gais, S, Born, J. Sleep-dependent declarative memory consolidation – unaffected after blocking NMDA or AMPA receptors but enhanced by NMDA coagonist D-cycloserine. Neuropsychopharmacology. 2013;38:2688–97.Google Scholar
Kuriyama, K, Honma, M, Shimazaki, M, Horie, M, Yoshiike, T, Koyama, S, et al. An N-methyl-D-aspartate receptor agonist facilitates sleep-independent synaptic plasticity associated with working memory capacity enhancement. Scientific Reports. 2011:1–7.Google Scholar
Kuriyama, K, Honma, M, Koyama, S, Kim, Y. D-cycloserine facilitates procedural learning but not declarative learning in healthy humans: a randomized controlled trial of the effect of D-cycloserine and valproic acid on overnight properties in the performance of non-emotional memory tasks. Neurobiology of Learning and Memory. 2011;95:505–9.Google Scholar
Skvarc, DR, Dean, OM, Byrne, LK, Gray, L, Lane, S, Lewis, M, et al. The effect of N-acetylcysteine on human cognition – a systematic review. Neuroscience and Biobehavioral Reviews. 2017;78:4456.CrossRefGoogle ScholarPubMed
Lauterborn, JC, Palmer, LC, Jia, Y, Pham, DT, Hou, B, Wang, W, et al. Chronic ampakine treatments stimulate dendritic growth and promote learning in middle-aged rats. Journal of Neuroscience. 2016;36:1636–46.Google Scholar
Sarter, M, Bruno, JP. Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Research Reviews. 1997;23:2846.Google Scholar
Kilgard, MP, Merzenich, MM. Cortical map reorganization enabled by nucleus basalis activity. Science. 1998;279:1714–18.Google Scholar
Conner, JM, Culberson, A, Packowski, C, Chiba, AA, Tuszynski, MH. Lesions of the basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning. Neuron. 2003;38:819–29.Google Scholar
Drachman, DA, Leavitt, J. Human memory and the cholinergic system. Archives of Neurology. 1974;30:113–21.Google Scholar
Schneider, LS. Treatment of Alzheimer’s disease with cholinesterase inhibitors. Clin Geriatr Med. 2001;17:337–58.Google Scholar
Doody, RS, Geldmacher, DS, Gordon, B, Perdomo, CA, Pratt, RD, Donepezil Study Group. Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Archives of Neurology. 2001;58:427–33.Google Scholar
Grothe, M, Heinsen, H, Teipel, SJ. Atrophy of the cholinergic basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biological Psychiatry. 2012;71:805–13.Google Scholar
Repantis, D, Laisney, O, Heuser, I. Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacological Research. 2010;61:473–81.Google Scholar
Manye, Kf, McIntire, DD, Mann, DM, German, DC. Locus coeruleus cell loss in the aging human brain: a nonrandom process. Journal of Comparative Neurology. 1995;358:7987.Google Scholar
Ding, Y-S, Singhal, T, Planeta-Wilson, B, Gallezot, J-D, Nabulsi, N, Labaree, D, et al. PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S,S)-[(11)C]O-methylreboxetine and HRRT. Synapse. 2010;64:30–8.Google Scholar
Adhikarla, V, Zeng, F, Votaw, JR, Goodman, MM, Nye, JA. Compartmental modeling of [11C]MENET binding to the norepinephrine transporter in the healthy human brain. Nuclear Medicine and Biology. 2016;43:318–23.Google Scholar
Wang, M, Gamo, NJ, Yang, Y, Jin, LE, Wang, X-J, Laubach, M, et al. Neuronal basis of age-related working memory decline. Nature. 2011;476:210–13.Google Scholar
Wilson, RS, Nag, S, Boyle, PA, Hizel, LP, Yu, L, Buchman, AS, et al. Neural reserve, neural density in the locus ceruleus, and cognitive decline. Neurology. 2013;80:1202–8.Google Scholar
Barcelos, NM, Van Ness, PH, Wagner, AF, MacAvoy, MG, Mecca, AP, Anderson, GM, et al. Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial. Neurobiology of Aging. 2018;70:117–24.Google Scholar
Bäckman, L, Karlsson, S, Fischer, H, Karlsson, P, Brehmer, Y, Rieckmann, A, et al. Dopamine D1 receptors and age differences in brain activation during working memory. Neurobiology of Aging. 2011;32:1849–56.Google Scholar
Karrer, TM, Josef, AK, Mata, R, Morris, ED, Samanez-Larkin, GR. Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis. Neurobiology of Aging. 2017;57:3646.Google Scholar
Vihayraghavan, S, Wang, M, Birnbaum, SG, Williams, GV, Arnsten, AFT. Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nature Neuroscience. 2007;10:376–84.Google Scholar
Rodríguez, JJ, Noristani, HN, Verkhratsky, A. The serotonergic system in ageing and Alzheimer’s disease. Progress in Neurobiology. 2012;99:1541.Google Scholar
Nadeau, SE. Intentional disorders. In: Noseworthy, JH, editor. Neurological Therapeutics Principles and Practice, 2nd ed, vol. 3. Oxon: Informa Healthcare; 2006, pp. 3108–23.Google Scholar
Elithorn, A, Partridge, M, McKissock, W, Knight, GC. Discussion on psychosurgery. Proceedings of the Royal Society of Medicine. 1959;52:203–10.Google Scholar
Bechara, A, Damasio, H, Damasio, AR. Manipulation of dopamine and serotonin causes different effects on covert and overt decision-making. Society for Neuroscience Abstracts. 2001;27:126.Google Scholar
Miu, AC, Crisan, LG, Chis, A, Ungureanu, L, Druga, B, Vulturar, R. Somatic markers mediate the effect of serotonin transporter gene polymorphisms on Iowa Gambling Task. Genes, Brain and Behavior. 2012;11:398403.Google Scholar
McIntyre, RS, Lophaven, S, Olsen, CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. International Journal of Neuropsychopharmacology. 2014;17:1557–67.Google Scholar
Lisman, J, Grace, AA, Duzel, E. A neoHebbian framework for episodic memory: role of dopamine-dependent late LTP. Trends in Neuroscience. 2011;34:536–47.Google Scholar
Chowdhury, R, Guitart-Masip, M, Bunzeck, N, Dolan, RJ, Düzel, E. Dopamine modulates episodic memory persistence in old age. Journal of Neuroscience. 2012;32:14193–204.Google Scholar
Knecht, S, Breitenstein, C, Bushuven, S, Wailke, S, Kamping, S, Flöel, A, et al. Levodopa: faster and better word learning in normal humans. Annals of Neurology. 2004;56:20–6.Google Scholar
Flöel, A, Breitenstein, C, Hummel, F, Celnik, P, Gingert, C, Sawaki, L, et al. Dopaminergic influences on formation of a motor memory. Annals of Neurology. 2005;58:121–30.Google Scholar
Fresnoza, S, Paulus, W, Mitsche, MA, Kuo, M-F. Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans. Journal of Neuroscience. 2014;34:2744–53.Google ScholarPubMed
Brickman, AM, Khan, UA, Provenzano, FA, Yeung, L-K, Suzuki, W, Schroeter, H, et al. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nature Neuroscience. 2014;12:1798–803.Google Scholar
Spalding, KL, Bergmann, O, Alkass, K, Bernard, S, Salehpour, M, Huttner, HB, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell. 2013;153:1219–27.Google Scholar
Salvadores, N, Sanhueza, M, Manque, P, Court, FA. Axonal degeneration during aging and its functional role in neurodegenerative disorders. Frontiers in Neuroscience. 2017;11:121.Google Scholar
Clarke, LE, Liddelow, SA, Chakraborty, C, Münch, AE, Heiman, M, Barres, BA. Normal aging induces A1-like astrocyte reactivity. Proceedings of the National Academy of Sciences USA. 2018;115(8):e1896e1905.Google Scholar
Davidson, T, Tremblay, F. Age and hemispheric differences in trancallosal inhibition between motor cortices: an ipsilateral silent period study. BMC Neuroscience. 2013;14:62.Google Scholar
Shibuya, K, Park, SB, Geevasinga, N, Huynh, W, Simon, NG, Menon, P, et al. Threshold tracking transcranial magnetic stimulation: Effects of age and gender on motor cortical function. Clinical Neurophysiology. 2016;127:2355–61.CrossRefGoogle ScholarPubMed
Liu, H, Yang, Y, Xia, Y, Zhu, W, Leak, RK, Wei, Z, et al. Aging of cerebral white matter. Ageing Research Reviews. 2017;34:6476.Google Scholar
Bennett, IJ, Madden, DJ, Vaidya, CJ, Howard, DV, Howard, JH. Age-related differences in multiple measures of white matter integrity: a diffusion tensor imaging study of healthy aging. Human Brain Mapping. 2010;31:378–90.Google Scholar
Yeatman, JD, Wandell, BA, Mezer, AA. Lifespan maturation and degeneration of human brain white matter. Nature Communications. 2014 Sep 17;5:4932.Google Scholar
Serbruyns, L, Leunissen, I, van Ruitenbeek, P, Pauwels, L, Caeyenberghs, K, Solesio-Jofre, E, et al. Alterations in brain white matter contributing to age-related slowing of task switching performance: the role of radial diffusivity and magnetization transfer ratio. Human Brain Mapping. 2016;37:4084–98.Google Scholar
Shrager, Y, Levy, DA, Hopkins, RO, Squire, LR. Working memory and the organization of brain systems. J Neuroscience. 2008;28:4818–22.CrossRefGoogle ScholarPubMed
Macpherson, SE, Philips, LH, Della Sala, S. Age, executive function and social decision making: a dorsolateral prefrontal theory of cognitive aging. Psychology and Aging. 2002;17:598609.Google Scholar
Nadeau, SE. Hemispheric asymmetry: what, why, and at what cost? Journal of the International Neuropsychological Society. 2010;27:13.Google Scholar
Mascalchi, M, Toschi, N, Ginestroni, A, Giannelli, M, Nicolai, E, Aiello, M, et al. Gender, age-related, and regional differences of the magnetization transfer ratio of the cortical and subcortical brain gray matter. Journal of Magnetic Resonance Imaging. 2014;40:360–6.Google Scholar
Ramon y Cajal, S. Degeneration and Regeneration of the Nervous System. London: Oxford University Press; 1928.Google Scholar

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