Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Acting Before; A Combined Strategy to Counteract the Onset and Progression of Dementia

Author(s): Stefano D. Pizzi , Alberto Granzotto, Manuela Bomba, Valerio Frazzini, Marco Onofrj and Stefano L. Sensi*

Volume 17, Issue 9, 2020

Page: [790 - 804] Pages: 15

DOI: 10.2174/1567205017666201203085524

Price: $65

Abstract

Brain aging and aging-related neurodegenerative disorders are posing a significant challenge for health systems worldwide. To date, most of the therapeutic efforts aimed at counteracting dementiarelated behavioral and cognitive impairment have been focused on addressing putative determinants of the disease, such as β-amyloid or tau. In contrast, relatively little attention has been paid to pharmacological interventions aimed at restoring or promoting the synaptic plasticity of the aging brain. The review will explore and discuss the most recent molecular, structural/functional, and behavioral evidence that supports the use of non-pharmacological approaches as well as cognitive-enhancing drugs to counteract brain aging and early-stage dementia.

Keywords: Aging, β-amyloid, cognitive-enhancing drugs, dementia, fMRI, hyper-connectivity, neuronal reserve, tau, excitotoxicity, glutamate, cognitive stimulation, exercise.

[1]
Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. N Engl J Med 2013; 368(14): 1326-34.
[http://dx.doi.org/10.1056/NEJMsa1204629] [PMID: 23550670]
[2]
Jack CR Jr, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer’s disease: An updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013; 12(2): 207-16.
[http://dx.doi.org/10.1016/S1474-4422(12)70291-0] [PMID: 23332364]
[3]
Herrup K. Reimagining Alzheimer’s disease--an age-based hypothesis. J Neurosci 2010; 30(50): 16755-62.
[http://dx.doi.org/10.1523/JNEUROSCI.4521-10.2010] [PMID: 21159946]
[4]
Damoiseaux JS. Effects of aging on functional and structural brain connectivity. Neuroimage 2017; 160: 32-40.
[http://dx.doi.org/10.1016/j.neuroimage.2017.01.077] [PMID: 28159687]
[5]
Logothetis NK. What we can do and what we cannot do with fMRI. Nature 2008; 453(7197): 869-78.
[http://dx.doi.org/10.1038/nature06976] [PMID: 18548064]
[6]
D’Esposito M, Deouell LY, Gazzaley A. Alterations in the BOLD fMRI signal with ageing and disease: A challenge for neuroimaging. Nat Rev Neurosci 2003; 4(11): 863-72.
[http://dx.doi.org/10.1038/nrn1246] [PMID: 14595398]
[7]
Gordon BA, Zacks JM, Blazey T, et al. Task-evoked fMRI changes in attention networks are associated with preclinical Alzheimer’s disease biomarkers. Neurobiol Aging 2015; 36(5): 1771-9.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.01.019] [PMID: 25708908]
[8]
Spreng RN, Turner GR. The shifting architecture of cognition and brain function in older adulthood. Perspect Psychol Sci 2019; 14(4): 523-42.
[http://dx.doi.org/10.1177/1745691619827511] [PMID: 31013206]
[9]
Damoiseaux JS, Smith SM, Witter MP, et al. White matter tract integrity in aging and Alzheimer’s disease. Hum Brain Mapp 2009; 30(4): 1051-9.
[http://dx.doi.org/10.1002/hbm.20563] [PMID: 18412132]
[10]
Li KZ, Lindenberger U. Relations between aging sensory/sensorimotor and cognitive functions. Neurosci Biobehav Rev 2002; 26(7): 777-83.
[http://dx.doi.org/10.1016/S0149-7634(02)00073-8] [PMID: 12470689]
[11]
Hillary FG, Grafman JH. Injured brains and adaptive networks: The benefits and costs of hyperconnectivity. Trends Cogn Sci 2017; 21(5): 385-401.
[http://dx.doi.org/10.1016/j.tics.2017.03.003] [PMID: 28372878]
[12]
Lipsitz LA, Goldberger AL. Loss of ‘complexity’ and aging. Potential applications of fractals and chaos theory to senescence. JAMA 1992; 267(13): 1806-9.
[http://dx.doi.org/10.1001/jama.1992.03480130122036] [PMID: 1482430]
[13]
Baltes PB, Lindenberger U. Emergence of a powerful connection between sensory and cognitive functions across the adult life span: A new window to the study of cognitive aging? Psychol Aging 1997; 12(1): 12-21.
[http://dx.doi.org/10.1037/0882-7974.12.1.12] [PMID: 9100264]
[14]
Park DC, Reuter-Lorenz P. The adaptive brain: Aging and neurocognitive scaffolding. Annu Rev Psychol 2009; 60: 173-96.
[http://dx.doi.org/10.1146/annurev.psych.59.103006.093656] [PMID: 19035823]
[15]
Turner GR, Spreng RN. Executive functions and neurocognitive aging: Dissociable patterns of brain activity. Neurobiol Aging 2012; 33(4): 1-13.
[http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.005]
[16]
Berlingeri M, Sacheli L, Danelli L, et al. Neurofunctional and neuromorphological evidence of the lack of compensation in pathological aging. Behav Neurol 2010; 23(4): 185-7.
[http://dx.doi.org/10.1155/2010/892373] [PMID: 21422550]
[17]
Rajah MN, D’Esposito M. Region-specific changes in prefrontal function with age: A review of PET and fMRI studies on working and episodic memory. Brain 2005; 128(Pt 9): 1964-83.
[http://dx.doi.org/10.1093/brain/awh608] [PMID: 16049041]
[18]
Cabeza R. Hemispheric asymmetry reduction in older adults: The HAROLD model. Psychol Aging 2002; 17(1): 85-100.
[http://dx.doi.org/10.1037/0882-7974.17.1.85] [PMID: 11931290]
[19]
Cappell KA, Gmeindl L, Reuter-Lorenz PA. Age differences in prefontal recruitment during verbal working memory maintenance depend on memory load. Cortex 2010; 46(4): 462-73.
[http://dx.doi.org/10.1016/j.cortex.2009.11.009] [PMID: 20097332]
[20]
Schneider-Garces NJ, Gordon BA, Brumback-Peltz CR, et al. Span, CRUNCH, and beyond: working memory capacity and the aging brain. J Cogn Neurosci 2010; 22(4): 655-69.
[http://dx.doi.org/10.1162/jocn.2009.21230] [PMID: 19320550]
[21]
Davis SW, Dennis NA, Daselaar SM, Fleck MS, Cabeza R. Que PASA? The posterior-anterior shift in aging. Cereb Cortex 2008; 18(5): 1201-9.
[http://dx.doi.org/10.1093/cercor/bhm155] [PMID: 17925295]
[22]
Grady CL, Maisog JM, Horwitz B, et al. Age-related changes in cortical blood flow activation during visual processing of faces and location. J Neurosci 1994; 14(3 Pt 2): 1450-62.
[http://dx.doi.org/10.1523/JNEUROSCI.14-03-01450.1994] [PMID: 8126548]
[23]
Cabeza R, Daselaar SM, Dolcos F, Prince SE, Budde M, Nyberg L. Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval. Cereb Cortex 2004; 14(4): 364-75.
[http://dx.doi.org/10.1093/cercor/bhg133] [PMID: 15028641]
[24]
Madden DJ, Connelly SL, Pierce TW. Adult age differences in shifting focused attention. Psychol Aging 1994; 9(4): 528-38.
[http://dx.doi.org/10.1037/0882-7974.9.4.528] [PMID: 7893424]
[25]
Grady CL. Functional brain imaging and age-related changes in cognition. Biol Psychol 2000; 54(1-3): 259-81.
[http://dx.doi.org/10.1016/S0301-0511(00)00059-4] [PMID: 11035226]
[26]
Levine BK, Beason-Held LL, Purpura KP, et al. Age-related differences in visual perception: A PET study. Neurobiol Aging 2000; 21(4): 577-84.
[http://dx.doi.org/10.1016/S0197-4580(00)00144-5] [PMID: 10924775]
[27]
Huettel SA, Singerman JD, McCarthy G. The effects of aging upon the hemodynamic response measured by functional MRI. Neuroimage 2001; 13(1): 161-75.
[http://dx.doi.org/10.1006/nimg.2000.0675] [PMID: 11133319]
[28]
Iidaka T, Okada T, Murata T, et al. Age-related differences in the medial temporal lobe responses to emotional faces as revealed by fMRI. Hippocampus 2002; 12(3): 352-62.
[http://dx.doi.org/10.1002/hipo.1113] [PMID: 12099486]
[29]
Nyberg L, Sandblom J, Jones S, et al. Neural correlates of training-related memory improvement in adulthood and aging. Proc Natl Acad Sci USA 2003; 100(23): 13728-33.
[http://dx.doi.org/10.1073/pnas.1735487100] [PMID: 14597711]
[30]
Meulenbroek O, Petersson KM, Voermans N, Weber B, Fernández G. Age differences in neural correlates of route encoding and route recognition. Neuroimage 2004; 22(4): 1503-14.
[http://dx.doi.org/10.1016/j.neuroimage.2004.04.007] [PMID: 15275907]
[31]
Grossman M, Cooke A, DeVita C, et al. Age-related changes in working memory during sentence comprehension: An fMRI study. Neuroimage 2002; 15(2): 302-17.
[http://dx.doi.org/10.1006/nimg.2001.0971] [PMID: 11798267]
[32]
Rypma B, D’Esposito M. Isolating the neural mechanisms of age-related changes in human working memory. Nat Neurosci 2000; 3(5): 509-15.
[http://dx.doi.org/10.1038/74889] [PMID: 10769393]
[33]
Anderson ND, Iidaka T, Cabeza R, Kapur S, McIntosh AR, Craik FI. The effects of divided attention on encoding- and retrieval-related brain activity: A PET study of younger and older adults. J Cogn Neurosci 2000; 12(5): 775-92.
[http://dx.doi.org/10.1162/089892900562598] [PMID: 11054920]
[34]
Grady CL, McIntosh AR, Horwitz B, et al. Age-related reductions in human recognition memory due to impaired encoding. Science 1995; 269(5221): 218-21.
[http://dx.doi.org/10.1126/science.7618082] [PMID: 7618082]
[35]
Gutchess AH, Welsh RC, Hedden T, et al. Aging and the neural correlates of successful picture encoding: Frontal activations compensate for decreased medial-temporal activity. J Cogn Neurosci 2005; 17(1): 84-96.
[http://dx.doi.org/10.1162/0898929052880048] [PMID: 15701241]
[36]
Cabeza R, Grady CL, Nyberg L, et al. Age-related differences in neural activity during memory encoding and retrieval: A positron emission tomography study. J Neurosci 1997; 17(1): 391-400.
[http://dx.doi.org/10.1523/JNEUROSCI.17-01-00391.1997] [PMID: 8987764]
[37]
Daselaar SM, Fleck MS, Dobbins IG, Madden DJ, Cabeza R. Effects of healthy aging on hippocampal and rhinal memory functions: An event-related fMRI study. Cereb Cortex 2006; 16(12): 1771-82.
[http://dx.doi.org/10.1093/cercor/bhj112] [PMID: 16421332]
[38]
Morcom AM, Henson RNA. Increased prefrontal activity with aging reflects nonspecific neural responses rather than compensation. J Neurosci 2018; 38(33): 7303-13.
[http://dx.doi.org/10.1523/JNEUROSCI.1701-17.2018] [PMID: 30037829]
[39]
Reuter-Lorenz PA, Park DC. How does it STAC up? Revisiting the scaffolding theory of aging and cognition. Neuropsychol Rev 2014; 24(3): 355-70.
[http://dx.doi.org/10.1007/s11065-014-9270-9] [PMID: 25143069]
[40]
Fabiani M. It was the best of times, it was the worst of times: A psychophysiologist’s view of cognitive aging. Psychophysiology 2012; 49(3): 283-304.
[http://dx.doi.org/10.1111/j.1469-8986.2011.01331.x] [PMID: 22220910]
[41]
Walhovd KB, Fjell AM, Espeseth T. Cognitive decline and brain pathology in aging-need for a dimensional, lifespan and systems vulnerability view. Scand J Psychol 2014; 55(3): 244-54.
[http://dx.doi.org/10.1111/sjop.12120] [PMID: 24730622]
[42]
Grady C. The cognitive neuroscience of ageing. Nat Rev Neurosci 2012; 13(7): 491-505.
[http://dx.doi.org/10.1038/nrn3256] [PMID: 22714020]
[43]
Kramer AF, Colcombe SJ, McAuley E, Scalf PE, Erickson KI. Fitness, aging and neurocognitive function. Neurobiol Aging 2005; 26(1): 124-7.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.09.009] [PMID: 16213062]
[44]
Pesonen AK, Eriksson JG, Heinonen K, et al. Cognitive ability and decline after early life stress exposure. Neurobiol Aging 2013; 34(6): 1674-9.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.12.012] [PMID: 23337341]
[45]
Martins R, Joanette Y, Monchi O. The implications of age-related neurofunctional compensatory mechanisms in executive function and language processing including the new Temporal Hypothesis for Compensation. Front Hum Neurosci 2015; 9: 221.
[http://dx.doi.org/10.3389/fnhum.2015.00221] [PMID: 25964754]
[46]
Braver TS. The variable nature of cognitive control: A dual mechanisms framework. Trends Cogn Sci 2012; 16(2): 106-13.
[http://dx.doi.org/10.1016/j.tics.2011.12.010] [PMID: 22245618]
[47]
Turner GR, Spreng RN. Prefrontal engagement and reduced default network suppression co-occur and are dynamically coupled in older adults: The default-executive coupling hypothesis of aging. J Cogn Neurosci 2015; 27(12): 2462-76.
[http://dx.doi.org/10.1162/jocn_a_00869] [PMID: 26351864]
[48]
Newman ME. Modularity and community structure in networks. Proc Natl Acad Sci USA 2006; 103(23): 8577-82.
[http://dx.doi.org/10.1073/pnas.0601602103] [PMID: 16723398]
[49]
Latora V, Marchiori M. Efficient behavior of small-world networks. Phys Rev Lett 2001; 87(19)198701
[http://dx.doi.org/10.1103/PhysRevLett.87.198701] [PMID: 11690461]
[50]
Achard S, Bullmore E. Efficiency and cost of economical brain functional networks. PLOS Comput Biol 2007; 3(2)e17
[http://dx.doi.org/10.1371/journal.pcbi.0030017] [PMID: 17274684]
[51]
Geerligs L, Renken RJ, Saliasi E, Maurits NM, Lorist MM. A brain-wide study of age-related changes in functional connectivity. Cereb Cortex 2015; 25(7): 1987-99.
[http://dx.doi.org/10.1093/cercor/bhu012] [PMID: 24532319]
[52]
Andrews-Hanna JR, Snyder AZ, Vincent JL, et al. Disruption of large-scale brain systems in advanced aging. Neuron 2007; 56(5): 924-35.
[http://dx.doi.org/10.1016/j.neuron.2007.10.038] [PMID: 18054866]
[53]
Allen EA, Erhardt EB, Damaraju E, et al. A baseline for the multivariate comparison of resting-state networks. Front Syst Neurosci 2011; 5: 2.
[http://dx.doi.org/10.3389/fnsys.2011.00002] [PMID: 21442040]
[54]
Bluhm RL, Osuch EA, Lanius RA, et al. Default mode network connectivity: Effects of age, sex, and analytic approach. Neuroreport 2008; 19(8): 887-91.
[http://dx.doi.org/10.1097/WNR.0b013e328300ebbf] [PMID: 18463507]
[55]
Damoiseaux JS, Beckmann CF, Arigita EJ, et al. Reduced resting-state brain activity in the “default network” in normal aging. Cereb Cortex 2008; 18(8): 1856-64.
[http://dx.doi.org/10.1093/cercor/bhm207] [PMID: 18063564]
[56]
Esposito R, Cilli F, Pieramico V, et al. Acute effects of modafinil on brain resting state networks in young healthy subjects. PLoS One 2013; 8(7)e69224
[http://dx.doi.org/10.1371/journal.pone.0069224] [PMID: 23935959]
[57]
Grady C, Sarraf S, Saverino C, Campbell K. Age differences in the functional interactions among the default, frontoparietal control, and dorsal attention networks. Neurobiol Aging 2016; 41: 159-72.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.02.020] [PMID: 27103529]
[58]
Hafkemeijer A, Altmann-Schneider I, Oleksik AM, et al. Increased functional connectivity and brain atrophy in elderly with subjective memory complaints. Brain Connect 2013; 3(4): 353-62.
[http://dx.doi.org/10.1089/brain.2013.0144] [PMID: 23627661]
[59]
Huang P, Fang R, Li BY, Chen SD. Exercise-related changes of networks in aging and mild cognitive impairment brain. Front Aging Neurosci 2016; 8: 47.
[http://dx.doi.org/10.3389/fnagi.2016.00047] [PMID: 27014055]
[60]
Koch W, Teipel S, Mueller S, et al. Effects of aging on default mode network activity in resting state fMRI: does the method of analysis matter? Neuroimage 2010; 51(1): 280-7.
[http://dx.doi.org/10.1016/j.neuroimage.2009.12.008] [PMID: 20004726]
[61]
Mevel K, Chételat G, Eustache F, Desgranges B. The default mode network in healthy aging and Alzheimer’s disease. Int J Alzheimers Dis 2011; 2011535816
[http://dx.doi.org/10.4061/2011/535816] [PMID: 21760988]
[62]
Mowinckel AM, Espeseth T, Westlye LT. Network-specific effects of age and in-scanner subject motion: A resting-state fMRI study of 238 healthy adults. Neuroimage 2012; 63(3): 1364-73.
[http://dx.doi.org/10.1016/j.neuroimage.2012.08.004] [PMID: 22992492]
[63]
Spreng RN, Stevens WD, Viviano JD, Schacter DL. Attenuated anticorrelation between the default and dorsal attention networks with aging: Evidence from task and rest. Neurobiol Aging 2016; 45: 149-60.
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.05.020] [PMID: 27459935]
[64]
Tomasi D, Volkow ND, Wang GJ, et al. Methylphenidate enhances brain activation and deactivation responses to visual attention and working memory tasks in healthy controls. Neuroimage 2011; 54(4): 3101-10.
[http://dx.doi.org/10.1016/j.neuroimage.2010.10.060] [PMID: 21029780]
[65]
Guise KG, Shapiro ML. Medial prefrontal cortex reduces memory interference by modifying hippocampal encoding. Neuron 2017; 94(1): 183-92.
[http://dx.doi.org/10.1016/j.neuron.2017.03.011]
[66]
Delli Pizzi S, Punzi M, Sensi SL. Alzheimer’s Disease Neuroimaging Initiative. Functional signature of conversion of patients with mild cognitive impairment. Neurobiol Aging 2019; 74: 21-37.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.10.004] [PMID: 30408719]
[67]
Zhou Y, Dougherty JH Jr, Hubner KF, Bai B, Cannon RL, Hutson RK. Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer’s disease and mild cognitive impairment. Alzheimers Dement 2008; 4(4): 265-70.
[http://dx.doi.org/10.1016/j.jalz.2008.04.006] [PMID: 18631977]
[68]
Grady CL, Protzner AB, Kovacevic N, et al. A multivariate analysis of age-related differences in default mode and task-positive networks across multiple cognitive domains. Cereb Cortex 2010; 20(6): 1432-47.
[http://dx.doi.org/10.1093/cercor/bhp207] [PMID: 19789183]
[69]
Lustig C, Snyder AZ, Bhakta M, et al. Functional deactivations: Change with age and dementia of the Alzheimer type. Proc Natl Acad Sci USA 2003; 100(24): 14504-9.
[http://dx.doi.org/10.1073/pnas.2235925100] [PMID: 14608034]
[70]
Persson J, Pudas S, Nilsson LG, Nyberg L. Longitudinal assessment of default-mode brain function in aging. Neurobiol Aging 2014; 35(9): 2107-17.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.03.012] [PMID: 24767950]
[71]
Sambataro F, Safrin M, Lemaitre HS, et al. Normal aging modulates prefrontoparietal networks underlying multiple memory processes. Eur J Neurosci 2012; 36(11): 3559-67.
[http://dx.doi.org/10.1111/j.1460-9568.2012.08254.x] [PMID: 22909094]
[72]
Anticevic A, Cole MW, Murray JD, Corlett PR, Wang XJ, Krystal JH. The role of default network deactivation in cognition and disease. Trends Cogn Sci 2012; 16(12): 584-92.
[http://dx.doi.org/10.1016/j.tics.2012.10.008] [PMID: 23142417]
[73]
Sala-Llonch R, Bartrés-Faz D, Junqué C. Reorganization of brain networks in aging: A review of functional connectivity studies. Front Psychol 2015; 6: 663.
[http://dx.doi.org/10.3389/fpsyg.2015.00663] [PMID: 26052298]
[74]
Li K, Laird AR, Price LR, et al. Progressive bidirectional age-related changes in default mode network effective connectivity across six decades. Front Aging Neurosci 2016; 8: 137.
[http://dx.doi.org/10.3389/fnagi.2016.00137] [PMID: 27378909]
[75]
Tsvetanov KA, Henson RN, Tyler LK, et al. The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults. Hum Brain Mapp 2015; 36(6): 2248-69.
[http://dx.doi.org/10.1002/hbm.22768] [PMID: 25727740]
[76]
Peng SL, Dumas JA, Park DC, et al. Age-related increase of resting metabolic rate in the human brain. Neuroimage 2014; 98: 176-83.
[http://dx.doi.org/10.1016/j.neuroimage.2014.04.078] [PMID: 24814209]
[77]
Lu B, Nagappan G, Guan X, Nathan PJ, Wren P. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci 2013; 14(6): 401-16.
[http://dx.doi.org/10.1038/nrn3505] [PMID: 23674053]
[78]
De Vis JB, Hendrikse J, Bhogal A, Adams A, Kappelle LJ, Petersen ET. Age-related changes in brain hemodynamics; A calibrated MRI study. Hum Brain Mapp 2015; 36(10): 3973-87.
[http://dx.doi.org/10.1002/hbm.22891] [PMID: 26177724]
[79]
Grinband J, Steffener J, Razlighi QR, Stern Y. BOLD neurovascular coupling does not change significantly with normal aging. Hum Brain Mapp 2017; 38(7): 3538-51.
[http://dx.doi.org/10.1002/hbm.23608] [PMID: 28419680]
[80]
Stagg CJ, Bachtiar V, Amadi U, et al. Local GABA concentration is related to network-level resting functional connectivity. eLife 2014; 3e01465
[http://dx.doi.org/10.7554/eLife.01465] [PMID: 24668166]
[81]
Delli Pizzi S, Chiacchiaretta P, Mantini D, et al. Functional and neurochemical interactions within the amygdala-medial prefrontal cortex circuit and their relevance to emotional processing. Brain Struct Funct 2017; 222(3): 1267-79.
[http://dx.doi.org/10.1007/s00429-016-1276-z] [PMID: 27566606]
[82]
Northoff G, Walter M, Schulte RF, et al. GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI. Nat Neurosci 2007; 10(12): 1515-7.
[http://dx.doi.org/10.1038/nn2001] [PMID: 17982452]
[83]
Delli Pizzi S, Chiacchiaretta P, Mantini D, et al. GABA content within medial prefrontal cortex predicts the variability of fronto-limbic effective connectivity. Brain Struct Funct 2017; 222(7): 3217-29.
[http://dx.doi.org/10.1007/s00429-017-1399-x] [PMID: 28386778]
[84]
Schultz AP, Chhatwal JP, Hedden T, et al. Phases of hyperconnectivity and hypoconnectivity in the default mode and salience networks track with amyloid and tau in clinically normal individuals. J Neurosci 2017; 37(16): 4323-31.
[http://dx.doi.org/10.1523/JNEUROSCI.3263-16.2017] [PMID: 28314821]
[85]
Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 280-92.
[http://dx.doi.org/10.1016/j.jalz.2011.03.003] [PMID: 21514248]
[86]
Katzman R, Terry R, DeTeresa R, et al. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 1988; 23(2): 138-44.
[http://dx.doi.org/10.1002/ana.410230206] [PMID: 2897823]
[87]
Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc 2002; 8(3): 448-60.
[http://dx.doi.org/10.1017/S1355617702813248] [PMID: 11939702]
[88]
Stern Y. Cognitive reserve and Alzheimer disease Alzheimer Dis Assoc Disord 2006; 20(3)(2):: S69-74.
[http://dx.doi.org/10.1097/00002093-200607001-00010] [PMID: 16917199]
[89]
Stern Y. Cognitive reserve. Neuropsychologia 2009; 47(10): 2015-28.
[http://dx.doi.org/10.1016/j.neuropsychologia.2009.03.004] [PMID: 19467352]
[90]
Nyberg L, Lövdén M, Riklund K, Lindenberger U, Bäckman L. Memory aging and brain maintenance. Trends Cogn Sci 2012; 16(5): 292-305.
[http://dx.doi.org/10.1016/j.tics.2012.04.005] [PMID: 22542563]
[91]
Barulli D, Stern Y. Efficiency, capacity, compensation, maintenance, plasticity: Emerging concepts in cognitive reserve. Trends Cogn Sci 2013; 17(10): 502-9.
[http://dx.doi.org/10.1016/j.tics.2013.08.012] [PMID: 24018144]
[92]
Habeck C, Hilton HJ, Zarahn E, Flynn J, Moeller J, Stern Y. Relation of cognitive reserve and task performance to expression of regional covariance networks in an event-related fMRI study of nonverbal memory. Neuroimage 2003; 20(3): 1723-33.
[http://dx.doi.org/10.1016/j.neuroimage.2003.07.032] [PMID: 14642482]
[93]
Habeck C, Rakitin BC, Moeller J, et al. An event-related fMRI study of the neural networks underlying the encoding, maintenance, and retrieval phase in a delayed-match-to-sample task. Brain Res Cogn Brain Res 2005; 23(2-3): 207-20.
[http://dx.doi.org/10.1016/j.cogbrainres.2004.10.010] [PMID: 15820629]
[94]
Stern Y. An approach to studying the neural correlates of reserve. Brain Imaging Behav 2017; 11(2): 410-6.
[http://dx.doi.org/10.1007/s11682-016-9566-x] [PMID: 27450378]
[95]
Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol 2012; 11(11): 1006-12.
[http://dx.doi.org/10.1016/S1474-4422(12)70191-6] [PMID: 23079557]
[96]
Blumen HM, Gazes Y, Habeck C, et al. Neural networks associated with the speed-accuracy tradeoff: Evidence from the response signal method. Behav Brain Res 2011; 224(2): 397-402.
[http://dx.doi.org/10.1016/j.bbr.2011.06.004] [PMID: 21699922]
[97]
Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol 2018; 14(11): 653-66.
[http://dx.doi.org/10.1038/s41582-018-0070-3] [PMID: 30291317]
[98]
Floud S, Simpson RF, Balkwill A, et al. Body mass index, diet, physical inactivity, and the incidence of dementia in 1 million UK women. Neurology 2020; 94(2): e123-32.
[http://dx.doi.org/10.1212/WNL.0000000000008779] [PMID: 31852815]
[99]
Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA 2018; 320(7): 657-64.
[http://dx.doi.org/10.1001/jama.2018.11499] [PMID: 30140876]
[100]
Sensi SL. Alzheimer’s Disease, time to turn the tide. Aging 2018; 10(10): 2537-8.
[http://dx.doi.org/10.18632/aging.101581] [PMID: 30317224]
[101]
Calfio C, Gonzalez A, Singh SK, Rojo LE, Maccioni RB. The emerging role of nutraceuticals and phytochemicals in the prevention and treatment of Alzheimer’s disease. J Alzheimers Dis 2020; 77(1): 33-51.
[http://dx.doi.org/10.3233/JAD-200443] [PMID: 32651325]
[102]
Poscia A, Milovanovic S, La Milia DI, et al. Effectiveness of nutritional interventions addressed to elderly persons: Umbrella systematic review with meta-analysis. Eur J Public Health 2018; 28(2): 275-83.
[http://dx.doi.org/10.1093/eurpub/ckx199] [PMID: 29228152]
[103]
Rosario D, Boren J, Uhlen M, et al. Systems biology approaches to understand the host-microbiome interactions in neurodegenerative diseases. Front Neurosci 2020; 14: 716.
[http://dx.doi.org/10.3389/fnins.2020.00716] [PMID: 32733199]
[104]
Scarmeas N, Anastasiou CA, Yannakoulia M. Nutrition and prevention of cognitive impairment. Lancet Neurol 2018; 17(11): 1006-15.
[http://dx.doi.org/10.1016/S1474-4422(18)30338-7] [PMID: 30244829]
[105]
Andrieu S, Guyonnet S, Coley N, et al. MAPT Study Group. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): A randomised, placebo-controlled trial. Lancet Neurol 2017; 16(5): 377-89.
[http://dx.doi.org/10.1016/S1474-4422(17)30040-6] [PMID: 28359749]
[106]
Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomized controlled trial. Lancet 2015; 385(9984): 2255-63.
[http://dx.doi.org/10.1016/S0140-6736(15)60461-5] [PMID: 25771249]
[107]
Hooshmand B, Mangialasche F, Kalpouzos G, et al. Association of vitamin B12, folate, and sulfur amino acids with brain magnetic resonance imaging measures in older adults: A longitudinal population-based study. JAMA Psychiatry 2016; 73(6): 606-13.
[http://dx.doi.org/10.1001/jamapsychiatry.2016.0274] [PMID: 27120188]
[108]
Onaolapo AY, Obelawo AY, Onaolapo OJ. Brain ageing, cognition and diet: A review of the emerging roles of food-based nootropics in mitigating age-related memory decline. Curr Aging Sci 2019; 12(1): 2-14.
[http://dx.doi.org/10.2174/1874609812666190311160754] [PMID: 30864515]
[109]
Bamidis PD, Vivas AB, Styliadis C, et al. A review of physical and cognitive interventions in aging. Neurosci Biobehav Rev 2014; 44: 206-20.
[http://dx.doi.org/10.1016/j.neubiorev.2014.03.019] [PMID: 24705268]
[110]
Boyke J, Driemeyer J, Gaser C, Büchel C, May A. Training-induced brain structure changes in the elderly. J Neurosci 2008; 28(28): 7031-5.
[http://dx.doi.org/10.1523/JNEUROSCI.0742-08.2008] [PMID: 18614670]
[111]
Pieramico V, Esposito R, Sensi F, et al. Combination training in aging individuals modifies functional connectivity and cognition, and is potentially affected by dopamine-related genes. PLoS One 2012; 7(8)e43901
[http://dx.doi.org/10.1371/journal.pone.0043901] [PMID: 22937122]
[112]
Grande G, Qiu C, Fratiglioni L. Prevention of dementia in an ageing world: Evidence and biological rationale. Ageing Res Rev 2020; 64101045
[http://dx.doi.org/10.1016/j.arr.2020.101045] [PMID: 32171784]
[113]
McMaster M, Kim S, Clare L, Torres SJ, D’Este C, Anstey KJ. Body, Brain, Life for Cognitive Decline (BBL-CD): Protocol for a multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment. Clin Interv Aging 2018; 13: 2397-406.
[http://dx.doi.org/10.2147/CIA.S182046] [PMID: 30538436]
[114]
Rosenberg A, Mangialasche F, Ngandu T, Solomon A, Kivipelto M. Multidomain interventions to prevent cognitive impairment, alzheimer’s disease, and dementia: From FINGER to World-Wide FINGERS. J Prev Alzheimers Dis 2020; 7(1): 29-36.
[PMID: 32010923]
[115]
Kivipelto M, Mangialasche F, Snyder HM, et al. World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia. Alzheimers Dement 2020; 16(7): 1078-94.
[http://dx.doi.org/10.1002/alz.12123] [PMID: 32627328]
[116]
Cotman CW, Berchtold NC. Exercise: A behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25(6): 295-301.
[http://dx.doi.org/10.1016/S0166-2236(02)02143-4] [PMID: 12086747]
[117]
van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2(3): 266-70.
[http://dx.doi.org/10.1038/6368] [PMID: 10195220]
[118]
Kleemeyer MM, Polk TA, Schaefer S, Bodammer NC, Brechtel L, Lindenberger U. Exercise-induced fitness changes correlate with changes in neural specificity in older adults. Front Hum Neurosci 2017; 11: 123.
[http://dx.doi.org/10.3389/fnhum.2017.00123] [PMID: 28360850]
[119]
Colcombe SJ, Kramer AF, Erickson KI, et al. Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci USA 2004; 101(9): 3316-21.
[http://dx.doi.org/10.1073/pnas.0400266101] [PMID: 14978288]
[120]
Suwabe K, Byun K, Hyodo K, et al. Rapid stimulation of human dentate gyrus function with acute mild exercise. Proc Natl Acad Sci USA 2018; 115(41): 10487-92.
[http://dx.doi.org/10.1073/pnas.1805668115] [PMID: 30249651]
[121]
World Health Organization. Risk reduction of cognitive decline and ementia: WHO guidelines. 2019.
[122]
Buchman AS, Yu L, Boyle PA, Schneider JA, De Jager PL, Bennett DA. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology 2016; 86(8): 735-41.
[http://dx.doi.org/10.1212/WNL.0000000000002387] [PMID: 26819457]
[123]
Canivet A, Albinet CT, André N, et al. Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: A cross sectional study. Eur Rev Aging Phys Act 2015; 12: 15.
[http://dx.doi.org/10.1186/s11556-015-0159-2] [PMID: 26865879]
[124]
Bomba M, Granzotto A, Castelli V, et al. Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis in adult mice. Neurobiol Aging 2018; 64: 33-43.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.12.009] [PMID: 29331730]
[125]
Choi SH, Bylykbashi E, Chatila ZK, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science 2018; 361(6406)eaan8821
[http://dx.doi.org/10.1126/science.aan8821] [PMID: 30190379]
[126]
Corona C, Masciopinto F, Silvestri E, et al. Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction. Cell Death Dis 2010; 1e91
[http://dx.doi.org/10.1038/cddis.2010.73] [PMID: 21368864]
[127]
Frazzini V, Granzotto A, Bomba M, et al. The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice. Sci Rep 2018; 8(1): 9768.
[http://dx.doi.org/10.1038/s41598-018-28083-9] [PMID: 29950603]
[128]
Weinstein G, Beiser AS, Choi SH, et al. Serum brain-derived neurotrophic factor and the risk for dementia: The Framingham Heart Study. JAMA Neurol 2014; 71(1): 55-61.
[http://dx.doi.org/10.1001/jamaneurol.2013.4781] [PMID: 24276217]
[129]
Mueller K, Arelin K, Möller HE, et al. Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain-a resting-state fMRI pilot study. Neurobiol Aging 2016; 38: 181-7.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.11.003] [PMID: 26827656]
[130]
Ashby FG, Valentin VV, von Meer SS. Differential effects of dopamine-directed treatments on cognition. Neuropsychiatr Dis Treat 2015; 11: 1859-75.
[http://dx.doi.org/10.2147/NDT.S65875] [PMID: 26251602]
[131]
Suo C, Singh MF, Gates N, et al. Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise. Mol Psychiatry 2016; 21(11): 1633-42.
[http://dx.doi.org/10.1038/mp.2016.19] [PMID: 27001615]
[132]
De Marco M, Meneghello F, Pilosio C, Rigon J, Venneri A. Up-regulation of DMN connectivity in mild cognitive impairment via network-based cognitive training. Curr Alzheimer Res 2018; 15(6): 578-89.
[http://dx.doi.org/10.2174/1567205015666171212103323] [PMID: 29231140]
[133]
Cao W, Cao X, Hou C, et al. Effects of cognitive training on resting-state functional connectivity of default mode, salience, and central executive networks. Front Aging Neurosci 2016; 8: 70.
[http://dx.doi.org/10.3389/fnagi.2016.00070] [PMID: 27148042]
[134]
Kirchhoff BA, Anderson BA, Barch DM, Jacoby LL. Cognitive and neural effects of semantic encoding strategy training in older adults. Cereb Cortex 2012; 22(4): 788-99.
[http://dx.doi.org/10.1093/cercor/bhr129] [PMID: 21709173]
[135]
Heinzel S, Rimpel J, Stelzel C, Rapp MA. Transfer effects to a multimodal dual-task after working memory training and associated neural correlates in older adults - A pilot study. Front Hum Neurosci 2017; 11: 85.
[http://dx.doi.org/10.3389/fnhum.2017.00085] [PMID: 28286477]
[136]
Kirchhoff BA, Anderson BA, Smith SE, Barch DM, Jacoby LL. Cognitive training-related changes in hippocampal activity associated with recollection in older adults. Neuroimage 2012; 62(3): 1956-64.
[http://dx.doi.org/10.1016/j.neuroimage.2012.06.017] [PMID: 22728150]
[137]
Luis EO, Arrondo G, Vidorreta M, et al. Successful working memory processes and cerebellum in an elderly sample: A Neuropsychological and fMRI Study. PLoS One 2015; 10(7)e0131536
[http://dx.doi.org/10.1371/journal.pone.0131536] [PMID: 26132286]
[138]
Battleday RM, Brem AK. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur Neuropsychopharmacol 2015; 25(11): 1865-81.
[http://dx.doi.org/10.1016/j.euroneuro.2015.07.028] [PMID: 26381811]
[139]
Brem AK, Sensi SL. Towards combinatorial approaches for preserving cognitive fitness in aging. Trends Neurosci 2018; 41(12): 885-97.
[http://dx.doi.org/10.1016/j.tins.2018.09.009] [PMID: 30343822]
[140]
Frey U, Morris RG. Synaptic tagging: Implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci 1998; 21(5): 181-8.
[http://dx.doi.org/10.1016/S0166-2236(97)01189-2] [PMID: 9610879]
[141]
Dannenberg H, Young K, Hasselmo M. Modulation of hippocampal circuits by muscarinic and nicotinic receptors. Front Neural Circuits 2017; 11: 102.
[http://dx.doi.org/10.3389/fncir.2017.00102] [PMID: 29321728]
[142]
Farr OM, Zhang S, Hu S, et al. The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults. Int J Neuropsychopharmacol 2014; 17(8): 1177-91.
[http://dx.doi.org/10.1017/S1461145714000674] [PMID: 24825078]
[143]
Linssen AM, Sambeth A, Vuurman EF, Riedel WJ. Cognitive effects of methylphenidate in healthy volunteers: A review of single dose studies. Int J Neuropsychopharmacol 2014; 17(6): 961-77.
[http://dx.doi.org/10.1017/S1461145713001594] [PMID: 24423151]
[144]
Klinge C, Shuttleworth C, Muglia P, Nobre AC, Harmer CJ, Murphy SE. Methylphenidate enhances implicit learning in healthy adults. J Psychopharmacol 2018; 32(1): 70-80.
[http://dx.doi.org/10.1177/0269881117731472] [PMID: 28946787]
[145]
Dockree PM, Barnes JJ, Matthews N, et al. The effects of methylphenidate on the neural signatures of sustained attention. Biol Psychiatry 2017; 82(9): 687-94.
[http://dx.doi.org/10.1016/j.biopsych.2017.04.016] [PMID: 28599833]
[146]
Drijgers RL, Verhey FR, Tissingh G, van Domburg PH, Aalten P, Leentjens AF. The role of the dopaminergic system in mood, motivation and cognition in Parkinson’s disease: A double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate. J Neurol Sci 2012; 320(1-2): 121-6.
[http://dx.doi.org/10.1016/j.jns.2012.07.015] [PMID: 22824349]
[147]
Müller U, Suckling J, Zelaya F, et al. Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes. Psychopharmacology (Berl) 2005; 180(4): 624-33.
[http://dx.doi.org/10.1007/s00213-005-2264-9] [PMID: 15830222]
[148]
Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ. Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl) 2003; 165(3): 260-9.
[http://dx.doi.org/10.1007/s00213-002-1250-8] [PMID: 12417966]
[149]
Carter RS, Geyer BC, Xie M, Acevedo-Suárez CA, Ballard DW. Persistent activation of NF-kappa B by the tax transforming protein involves chronic phosphorylation of IkappaB kinase subunits IKKbeta and IKKgamma. J Biol Chem 2001; 276(27): 24445-8.
[http://dx.doi.org/10.1074/jbc.C000777200] [PMID: 11325957]
[150]
Minzenberg MJ, Carter CS. Modafinil: A review of neurochemical actions and effects on cognition. Neuropsychopharmacology 2008; 33(7): 1477-502.
[http://dx.doi.org/10.1038/sj.npp.1301534] [PMID: 17712350]
[151]
Nagata T, Kobayashi N, Ishii J, et al. Association between DNA methylation of the BDNF promoter region and clinical presentation in Alzheimer’s disease. Dement Geriatr Cogn Disord Extra 2015; 5(1): 64-73.
[http://dx.doi.org/10.1159/000375367] [PMID: 25873928]
[152]
Dell’Osso B, Dobrea C, Cremaschi L, Arici C, Altamura AC. Wake-promoting pharmacotherapy for psychiatric disorders. Curr Psychiatry Rep 2014; 16(12): 524.
[http://dx.doi.org/10.1007/s11920-014-0524-2] [PMID: 25312027]
[153]
Schmidt KH, Gerlach D, Gubbe K, et al. Virulence of group A streptococci in fertile hens eggs is mainly effected by M protein and streptolysin O. Int J Med Microbiol 2001; 291(1): 45-56.
[http://dx.doi.org/10.1078/1438-4221-00102] [PMID: 11403411]
[154]
Punzi M, Gili T, Petrosini L, Caltagirone C, Spalletta G, Sensi SL. Modafinil-induced changes in functional connectivity in the cortex and cerebellum of healthy elderly subjects. Front Aging Neurosci 2017; 9: 85.
[http://dx.doi.org/10.3389/fnagi.2017.00085] [PMID: 28424611]
[155]
Lynch G, Cox CD, Gall CM. Pharmacological enhancement of memory or cognition in normal subjects. Front Syst Neurosci 2014; 8: 90.
[http://dx.doi.org/10.3389/fnsys.2014.00090] [PMID: 24904313]
[156]
Jurado S. AMPA receptor trafficking in natural and pathological aging. Front Mol Neurosci 2018; 10: 446.
[http://dx.doi.org/10.3389/fnmol.2017.00446] [PMID: 29375307]
[157]
Miyamoto S, Miyake N, Jarskog LF, Fleischhacker WW, Lieberman JA. Pharmacological treatment of schizophrenia: A critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry 2012; 17(12): 1206-27.
[http://dx.doi.org/10.1038/mp.2012.47] [PMID: 22584864]
[158]
Wezenberg E, Verkes RJ, Ruigt GS, Hulstijn W, Sabbe BG. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology 2007; 32(6): 1272-83.
[http://dx.doi.org/10.1038/sj.npp.1301257] [PMID: 17119538]
[159]
Beglinger LJ, Gaydos BL, Kareken DA, Tangphao-Daniels O, Siemers ER, Mohs RC. Neuropsychological test performance in healthy volunteers before and after donepezil administration. J Psychopharmacol 2004; 18(1): 102-8.
[http://dx.doi.org/10.1177/0269881104040248] [PMID: 15107192]
[160]
Wezenberg E, Verkes RJ, Sabbe BG, Ruigt GS, Hulstijn W. Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects. Psychopharmacology (Berl) 2005; 181(3): 582-94.
[http://dx.doi.org/10.1007/s00213-005-0083-7] [PMID: 16041534]
[161]
Yesavage JA, Friedman L, Ashford JW, et al. Acetylcholinesterase inhibitor in combination with cognitive training in older adults. J Gerontol B Psychol Sci Soc Sci 2008; 63(5): 288-94.
[http://dx.doi.org/10.1093/geronb/63.5.P288] [PMID: 18818443]
[162]
Sun Y, Yang Y, Galvin VC, Yang S, Arnsten AF, Wang M. Nicotinic α4β2 cholinergic receptor influences on dorsolateral prefrontal cortical neuronal firing during a Working Memory Task. J Neurosci 2017; 37(21): 5366-77.
[http://dx.doi.org/10.1523/JNEUROSCI.0364-17.2017] [PMID: 28450546]
[163]
Majdi A, Kamari F, Vafaee MS, Sadigh-Eteghad S. Revisiting nicotine’s role in the ageing brain and cognitive impairment. Rev Neurosci 2017; 28(7): 767-81.
[http://dx.doi.org/10.1515/revneuro-2017-0008] [PMID: 28586306]
[164]
Dunbar GC, Inglis F, Kuchibhatla R, Sharma T, Tomlinson M, Wamsley J. Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI). J Psychopharmacol 2007; 21(2): 171-8.
[http://dx.doi.org/10.1177/0269881107066855] [PMID: 17329297]
[165]
Dunbar GC, Kuchibhatla RV, Lee G. TC-1734 (AZD3480) AAMI Clinical Study Group (USA). A randomized double-blind study comparing 25 and 50 mg TC-1734 (AZD3480) with placebo, in older subjects with age-associated memory impairment. J Psychopharmacol 2011; 25(8): 1020-9.
[http://dx.doi.org/10.1177/0269881110367727] [PMID: 20542923]
[166]
Atri A, Frölich L, Ballard C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: Three randomized clinical trials. JAMA 2018; 319(2): 130-42.
[http://dx.doi.org/10.1001/jama.2017.20373] [PMID: 29318278]
[167]
Ly C, Greb AC, Cameron LP, et al. Psychedelics promote structural and functional neural plasticity. Cell Rep 2018; 23(11): 3170-82.
[http://dx.doi.org/10.1016/j.celrep.2018.05.022] [PMID: 29898390]
[168]
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums. Nat Rev Neurol 2018; 14(3): 168-81.
[http://dx.doi.org/10.1038/nrneurol.2017.185] [PMID: 29377010]
[169]
Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 2009; 5(6): 311-22.
[http://dx.doi.org/10.1038/nrneurol.2009.54] [PMID: 19498435]
[170]
Avgerinos KI, Kalaitzidis G, Malli A, Kalaitzoglou D, Myserlis PG, Lioutas VA. Intranasal insulin in Alzheimer’s dementia or mild cognitive impairment: A systematic review. J Neurol 2018; 265(7): 1497-510.
[http://dx.doi.org/10.1007/s00415-018-8768-0] [PMID: 29392460]
[171]
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: A pilot clinical trial. Arch Neurol 2012; 69(1): 29-38.
[http://dx.doi.org/10.1001/archneurol.2011.233] [PMID: 21911655]
[172]
Abbas T, Faivre E, Hölscher C. Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer’s disease. Behav Brain Res 2009; 205(1): 265-71.
[http://dx.doi.org/10.1016/j.bbr.2009.06.035] [PMID: 19573562]
[173]
Athauda D, Gulyani S, Karnati HK, et al. Utility of neuronal-derived exosomes to examine molecular mechanisms that affect motor function in patients With Parkinson Disease: A secondary analysis of the exenatide-PD trial. JAMA Neurol 2019; 76(4): 420-9.
[http://dx.doi.org/10.1001/jamaneurol.2018.4304] [PMID: 30640362]
[174]
Bomba M, Granzotto A, Castelli V, et al. Exenatide reverts the high-fat-diet-induced impairment of BDNF signaling and inflammatory response in an animal model of Alzheimer’s disease. J Alzheimers Dis 2019; 70(3): 793-810.
[http://dx.doi.org/10.3233/JAD-190237] [PMID: 31256135]
[175]
Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson’s disease: A randomised, double-blind, placebo-controlled trial. Lancet 2017; 390(10103): 1664-75.
[http://dx.doi.org/10.1016/S0140-6736(17)31585-4] [PMID: 28781108]
[176]
Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Exenatide and the treatment of patients with Parkinson’s disease. J Clin Invest 2013; 123(6): 2730-6.
[http://dx.doi.org/10.1172/JCI68295] [PMID: 23728174]
[177]
Bassil F, Fernagut PO, Bezard E, Meissner WG. Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: targets for disease modification? Prog Neurobiol 2014; 118: 1-18.
[http://dx.doi.org/10.1016/j.pneurobio.2014.02.005] [PMID: 24582776]
[178]
Haller S, Rodriguez C, Moser D, et al. Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: A BOLD and perfusion MRI study. Neuroscience 2013; 250: 364-71.
[http://dx.doi.org/10.1016/j.neuroscience.2013.07.021] [PMID: 23876323]
[179]
Villeda SA, Plambeck KE, Middeldorp J, et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med 2014; 20(6): 659-63.
[http://dx.doi.org/10.1038/nm.3569] [PMID: 24793238]
[180]
Sha SJ, Deutsch GK, Tian L, et al. Safety, tolerability, and feasibility of young plasma infusion in the plasma for alzheimer symptom amelioration study: A randomized clinical trial. JAMA Neurol 2019; 76(1): 35-40.
[http://dx.doi.org/10.1001/jamaneurol.2018.3288] [PMID: 30383097]
[181]
Greene JA, Loscalzo J. Putting the patient back together - social medicine, network medicine, and the limits of reductionism. N Engl J Med 2017; 377(25): 2493-9.
[http://dx.doi.org/10.1056/NEJMms1706744] [PMID: 29262277]
[182]
Loscalzo J, Kohane I, Barabasi AL. Human disease classification in the postgenomic era: A complex systems approach to human pathobiology. Mol Syst Biol 2007; 3: 124.
[http://dx.doi.org/10.1038/msb4100163] [PMID: 17625512]
[183]
Loscalzo J, Barabasi AL. Systems biology and the future of medicine. Wiley Interdiscip Rev Syst Biol Med 2011; 3(6): 619-27.
[http://dx.doi.org/10.1002/wsbm.144] [PMID: 21928407]
[184]
Scheltens P, Blennow K, Breteler MM, et al. Alzheimer’s disease. Lancet 2016; 388(10043): 505-17.
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[185]
Lane CA, Barnes J, Nicholas JM, et al. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. Lancet Neurol 2019; 18(10): 942-52.
[http://dx.doi.org/10.1016/S1474-4422(19)30228-5] [PMID: 31444142]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy