Physiological Basis of Memory Dysfunction in Alzheimer’s Disease – An Overview

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A. S. V. Prasad


Alzheimer’s disease (AD) is a neuro-degenerative disease, causing gradual decline in memory function in the affected patients. The loss of memory makes their existence miserable. It is first noticed and reported by the patient’s care takers. The clinicians objectively assess the type and degree of the memory loss by a specific battery of tests, specially designed for the purpose (like Montreal Cognitive Assessment (MoCA) test., Mini-Mental State Exam (MMSE etc.)). Understanding the symptoms of AD, arising out of memory loss, requires deeper insights into what initiates the memory (the sensory inputs from the five sense organs), the different types of memories (explicit, implicit memories, their sub types and associative memory etc.), how the memory signals are modified at the level of the neuron, (analog to digital signals) and the synapse (sensitization, habituation and Long term potentiation / depression etc.), the processing that the inputs received , undergo (encoding, consolidation /organization, storage and retrieval) in higher brain centres (amygdala, hippocampus prefrontal vortex etc.) and also the role played by the various receptors (NMDA, AMPA and the kinase receptors), the neurotransmitters (acetylcholine, Norepineprine, Gama aminobutic acid, serotonin etc.), the central network systems involved (central executive network, salience network, and the default mode network). In short, it is the study all about, of the physiology of memory. The next step is to integrate this knowledge to interpret symptoms of patients with AD. Accordingly, the subject under discussion is dealt with in two parts. Firstly, how the memory is affected in AD and secondly the physiology behind these changes.

Memory, cognition, explicit and implicit memory, long term potentiation, memory processing, neurotransmitters, synaptic receptors, central executive network.

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Prasad, A. S. V. (2020). Physiological Basis of Memory Dysfunction in Alzheimer’s Disease – An Overview. International Journal of Biochemistry Research & Review, 29(2), 9-24.
Review Article


Richard Gross. Psychology: The Science of Mind and Behaviour 6E, Hachette UK.

Petersen RC. Mild cognitive impairment. N Engl J Med. 2011;364:2227–34.

Farias ST, Mungas D, Reed BR, Harvey D, DeCarli C. Progression of mild cognitive impairment to dementia in clinic- vs. community-based cohorts. Arch Neurol. 2009;66:1151–7.

Rahayel S, Frasnelli J, Joubert S. The effect of Alzheimer's disease and Parkinson's disease on olfaction: A meta-analysis. Behav Brain Res. 2012;231:60.

Dialogues Clin Neurosci. 2013;15(4):445–454.

Prasad ASV. Essentials of anatomy as related to Alzheimer’s disease: A review. J Alzheimer’s Dis Parkinsonism. 2020;10: 486.

Braak H, Braak E. Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathology. 1996;92:197–201.

Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathologica. 1991;82:239–259.

Hyman BT, Vanhoesen GW, Damasio AR, Barnes CL. Alzheimers-disease - cell-specific pathology isolates the hippocampal formation. Science. 1984; 225:1168–1170.

Bondareff W, Mountjoy CQ, Roth M. Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology. 1982;32:164–168.

Mann DM, Yates PO, Marcyniuk B. A comparison of changes in the nucleus basalis and locus caeruleus in Alzheimer & apos;s disease. J Neurol Neurosurg Psychiatry. 1984;47.

AMA and Archives Journals. Reduced brain volume may predict dementia in healthy elderly people. Science Daily; 2006.

Jennifer L. Whitwell. The protective role of brain size in Alzheimer disease. Expert Rev Neurother. 2010;10(12):1799–1801.
PMCID: PMC3920660

Tascone LdS, Payne ME, MacFall J, Azevedo D, de Castro CC, Steffens DC, et al. Cortical brain volume abnormalities associated with few or multiple neuropsychiatric symptoms in Alzheimer’s disease. PLoS ONE. 2017;12(5): e0177169.

Kodl CT, Seaquist ER. Cognitive dysfunction and diabetes mellitus. Endocr Rev. 2008;29:494–511.

De Felice FG, et al. Neuroinflammation at the basis of cognitive impairment in Alzheimer & apos;s disease. Front Aging Neurosci; 2015.

Cox DJ, Kovatchev BP, Gonder-Frederick LA, Summers KH, McCall A, Grimm KJ, et al. Relationships between hyperglycemia and cognitive performance among adults with type 1 and type 2 diabetes. Diabetes Care. 2005;28:71–7.

Cukierman-Yaffe T, Gerstein HC, Williamson JD, Lazar RM, Lovato L, Miller ME, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: The action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009;32(2):221-6.

DeFronzo RA. In resistance, lipotoxicity, type 2 diabetes and atherosclerosis: The missing links. Diabetologia; 2010.

Banks PA, et al. Classification of acute pancreatitis--2012: Revision of the Atlanta classification and definitions by international consensus. Gut; 2013.

Klein JP, Waxman SG. The brain in diabetes: Molecular changes in neurons and their implications for end-organ damage. Lancet Neurol. 2003;2:548–54.

Doyle P, Cusin I, Rohner-Jeanrenaud F, Jeanrenaud B. Four-day hyperinsulinemia in euglycemic conditions alters local cerebral glucose utilization in specific brain nuclei of freely moving rats. Brain Res. 1995;684:47–55.

Lucignani G, Namba H, Nehlig A, Porrino LJ, Kennedy C, Sokoloff L. Effects of insulin on local cerebral glucose utilization in the rat. J Cereb Blood Flow Metab. 1987;7:309–14.

Ramakrishnan R, Sheeladevi R, Suthanthirarajan N. PKC-alpha mediated alterations of indoleamine contents in diabetic rat brain. Brain Res Bull. 2004;64:189–94.

Kamal A, Biessels GJ, Urban IJA, Gispen WH. Hippocampal synaptic plasticity in streptozotocin-diabetic rats: Impairment of long-term potentiation and facilitation of long-term depression. Neuroscience. 1999;90:737–45.

Welsh B, Wecker L. Effects of streptozotocin-induced diabetes on acetylcholine metabolism in rat brain. Neurochem Res. 1991;16:453–60.

Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gispen WH. Cerebral function in diabetes mellitus. Diabetologia. 1994;37:643–50.

Prasad ASV. The essentials of biochemistry of the proteins as related to Alzheimer’s disease: A review. International Journal of Biochemistry Research & Review. 2020;29(1)34-49.

Wongupparaj, Kumari, Morris. The relation between a multicomponent working memory and intelligence: The roles of central executive and short-term storage functions. Intelligence. 2015;53:166-180.

Menon V, Uddin LQ. Saliency, switching, attention and control: A network model of insula function. Brain Structure & Function. 2010;214(5–6):655–67.

Peters SK, Dunlop K, Downar J. Cortico-Striatal-Thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment. Frontiers in Systems Neuroscience. 2016;10:104.

Menon V. Salience network. In: Arthur W. Toga, Editor. Brain Mapping: An Encyclopedic Reference, Academic Press. 2015;2:597-611.

Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: Anatomy, function and relevance to disease. Ann N Y Acad Sci. 2008;1124:1.

Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural and functional characterization of Alzheimer's disease: Evidence for a relationship between default activity, amyloid and memory. J Neurosci. 2005;25:7709–7717.

Herholz K, Salmon E, Perani D, et al Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage. 2002;17:302–316.

Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009;66:435–440.

Palop JJ, Mucke L. Synaptic depression and aberrant excitatory network activity in Alzheimer's disease: Two faces of the same coin? Neuromolecular. Med. 2010; 12:48–55.

Palop JJ, Mucke L, Roberson ED. Quantifying biomarkers of cognitive dysfunction and neuronal network hyperexcitability in mouse models of Alzheimer's disease: Depletion of calcium-dependent proteins and inhibitory hippocampal remodelling. Methods Mol Biol. 2011;670:245–262. [Habituation]

Graf P, Schacter DL. Implicit and explicit memory for new associations in normal and amnesic subjects (PDF). Journal of Experimental Psychology: Learning, Memory, and Cognition. 1985;11.

Szpunar, Karl K. Episodic future thought. Perspectives on psychological science. SAGE Publications. 2010;5(2):142– 162.

Foerde K, Knowlton BJ, Poldrack RA. Modulation of competing memory systems by distraction. Proceedings of the National Academy of Sciences of the United States of America. Proceedings of the National Academy of Sciences. 2006;103(31): 11778–11783.

Jenkins HM. Animal learning and behavior theory. Ch. 5 in Hearst, E. "The First Century of Experimental Psychology" Hillsdale N. J., Earlbaum; 1979.

Rankin. Habituation mechanisms and their importance for cognitive function i. Front Integr Neurosci. 2014;8:97.
(Published Online 2015 Jan 8)

Shettleworth SJ. Cognition, Evolution and Behavior (2nd Ed.). New York: Oxford; 2010.

Tsien JZ. Memory and the NMDA receptors. N. Engl. J. Med. 2009;361(3): 302–3.

Whitlock JR, Heynen AJ, Shuler MG, Bear MF. Learning induces long-term potentiation in the hippocampus. Science. 2006;313(5790):1093–7.

Hebb DO. The organization of behavior. New York: Wiley. Baddeley A. The episodic buffer: A new component of working memory? Trends Cogn. Sci. (Regul. Ed.). 2000;4(11):417–423.

Kemp JA, McKernan RM. NMDA receptor pathways as drug targets. Nature Neuroscience. 2002;5(11):1039–1042.

Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nature Reviews Drug Discovery. 2006;5(2):160–170.

Glutamate receptors: Structures and functions. University of Bristol Centre for Synaptic Plasticity. Archived from the Original on 15 September; 2007.

Song I, Huganir RL. Regulation of AMPA receptors during synaptic plasticity. Trends Neurosci. 2002;25(11):578–88.

Pereira Alfredo Jr, Maria Alice Ornellas Pereira, Fábio Augusto Furlan. Recent advances in brain physiology and cognitive. Processingo Mens Sana Monogr. 2011;9(1):183–192.

Malenka RC, Nestler EJ, Hyman SE. Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin. In Sydor A, Brown RY, (Eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd Ed.). New York: McGraw-Hill Medical. 2009;147–148,154–157.