1. Murray, ME, Graff-Radford, NR, Ross, OA, Petersen, RC, Duara, R, Dickson, DW. Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011;10(9):785–796.
Google Scholar | Crossref | Medline | ISI2. v, an der Flier, WM, Pijnenburg, YA, Fox, NC, Scheltens, P. Early-onset versus late-onset Alzheimer’s disease: the case of the missing APOE ε4 allele. Lancet Neurol. 2011;10(3):280–288.
Google Scholar | Crossref | Medline3. Barnes, J, Dickerson, BC, Fr, ost, C, Jiskoot, LC, Wolk, D, van der Flier, WM. Alzheimer’s disease first symptoms are age dependent: evidence from the NACC dataset. Alzheimer’s Dement. 2015;11(11):1349–1357.
Google Scholar | Crossref | Medline4. Bolton, C, Lowe, J, Kutnar, K, Lane, C, Pyykkonen, B. Neuropsychological differentiation of early-onset and late-onset Alzheimer’s disease in autopsy-confirmed cases. Clin Neuropsychol. 2018;32(4):585.
Google Scholar5. Bolton, C, Pyykkonen, B. The relation of age and APOE genotype to clinical heterogeneity in early onset Alzheimer’s disease. Alzheimer’s Dement. 2019;15(7):449.
Google Scholar | Crossref6. Dickerson, BC, Brickhouse, M, McGinnis, S, Wolk, DA. Alzheimer’s disease: the influence of age on clinical heterogeneity through the human brain connectome. Alzheimers Dement Diagn Assess Dis Monit. 2016;6:122–135.
Google Scholar | Medline7. Joubert, S, Gour, N, Guedj, E, et al. Early-onset and late-onset Alzheimer’s disease are associated with distinct patterns of memory impairment. Cortex. 2016;74(Supplement C):217–232. doi:10.1016/j.cortex.2015.10.014
Google Scholar | Crossref | Medline8. Koedam, ELGE, Lauffer, V, Van der Vlies, AE, Van der Flier, WM, Scheltens, P, Pijnenburg, YAL. Early-versus late-onset Alzheimer’s disease: more than age alone. J Alzheimers Dis. 2010;19(4):1401–1408.
Google Scholar | Crossref | Medline | ISI9. Palasí, A, Gutiérrez-Iglesias, B, Alegret, M, et al. Differentiated clinical presentation of early and late-onset Alzheimer’s disease: is 65 years of age providing a reliable threshold? J Neurol. 2015;262(5):1238–1246.
Google Scholar | Crossref | Medline10. Smits, LL, Pijnenburg, YAL, van der Vlies, AE, et al. Early onset APOE E4-negative Alzheimer’s disease patients show faster cognitive decline on non-memory domains. Eur Neuropsychopharmacol. 2015;25(7):1010–1017.
Google Scholar | Crossref | Medline11. Mendez, MF, Lee, AS, Joshi, A, Shapira, JS. Nonamnestic presentations of early-onset Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2012;27(6):413–420.
Google Scholar | SAGE Journals | ISI12. Frisoni, GB, Pievani, M, Testa, C, et al. The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain. 2007;130(3):720–730.
Google Scholar | Crossref | Medline13. Karas, G, Scheltens, P, Rombouts, S, et al. Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study. Neuroradiology. 2007;49(12):967–976.
Google Scholar | Crossref | Medline | ISI14. Möller, C, Vrenken, H, Jiskoot, L, et al. Different patterns of gray matter atrophy in early- and late-onset Alzheimer’s disease. Neurobiol Aging. 2013;34(8):2014–2022.
Google Scholar | Crossref | Medline | ISI15. Verclytte, S, Lopes, R, Lenfant, P, et al. Cerebral hypoperfusion and hypometabolism detected by arterial spin labeling MRI and FDG-PET in early-onset Alzheimer’s disease. J Neuroimaging. 2016;26(2):207–212.
Google Scholar | Crossref | Medline16. Braak, H, Thal, DR, Ghebremedhin, E, Del Tredici, K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70(11):960–969.
Google Scholar | Crossref | Medline17. Zarow, C, Lyness, SA, Mortimer, JA, Chui, HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol. 2003;60(3):337. doi:10.1001/archneur.60.3.337
Google Scholar | Crossref | Medline18. Aston-Jones, G, Cohen, JD. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci. 2005;28:40–450.
Google Scholar | Crossref19. Coull, JT, Büchel, C, Friston, KJ, Frith, CD. Noradrenergically mediated plasticity in a human attentional neuronal network. NeuroImage. 1999;10(6):705–715.
Google Scholar | Crossref | Medline20. Murphy, PR, Robertson, IH, Balsters, JH, O’connell, RG. Pupillometry and P3 index the locus coeruleus-noradrenergic arousal function in humans. Psychophysiology. 2011;48(11):1532–1543.
Google Scholar | Crossref | Medline21. Sara, SJ . The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009;10(3):211–223.
Google Scholar | Crossref | Medline22. Moret, C, Briley, M. The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7(suppl 1):9–13.
Google Scholar | Medline23. Jacobs, D, Sano, M, Marder, K, et al. Age at onset of Alzheimer’s disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology. 1994;44(7):1215–1220.
Google Scholar | Crossref | Medline | ISI24. Ballarini, T, Iaccarino, L, Magnani, G, et al. Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer’s disease. Hum Brain Mapp. 2016;37(12):4234–4247.
Google Scholar | Crossref | Medline25. Hyman, BT, Trojanowski, JQ. Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the national institute on aging and the Reagan institute working group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol. 1997;56(10):1095–1097. doi:10.1097/00005072-199710000-00002
Google Scholar | Crossref | Medline26. Hyman, BT, Phelps, CH, Beach, TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8(1):1–13. doi:10.1016/j.jalz.2011.10.007
Google Scholar | Crossref | Medline | ISI27. Ellison, D, Love, S, Chimelli, L, et al. Parkinsonism and akinetic–rigid disorders. In: Neuropathology. 3rd ed. Elsevier; 2013, 567–585.
Google Scholar28. Weintraub, S, Salmon, D, Mercaldo, N, et al. The Alzheimer’s disease centers’ uniform data set (UDS): the neuropsychological test battery. Alzheimer Dis Assoc Disord. 2009;23(2):91–101.
Google Scholar | Crossref | Medline | ISI29. Shirk, SD, Mitchell, MB, Shaughnessy, LW, et al. A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery. Alzheimers Res Ther. 2011;3(6):32.
Google Scholar | Crossref | Medline30. Folstein, MF, Folstein, SE, McHugh, PR. “Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res. 1975;12(3):189–198.
Google Scholar | Crossref | Medline | ISI31. Wechsler, D . Wechsler Memory Scale-Revised Manual. The Psychological Corporation; 1987.
Google Scholar32. Wechsler, A . Wechsler Adult Intelligence Scale-Revised. Psychological Corporation; 1987.
Google Scholar33. Reitan, RM . Trail Making Test: Manual for Administration and Scoring. Reitan Neuropsychology Laboratory; 1992.
Google Scholar34. Kaplan, E, Goodglass, H, Weintraub, S. The Boston Naming Test. Philadelphia: Lea & Febiger; 1983.
Google Scholar35. Helmstaedter, C, Wietzke, J, Lutz, MT. Unique and shared validity of the “Wechsler logical memory test,” the “California verbal learning test,” and the “verbal learning and memory test” in patients with epilepsy. Epilepsy Res. 2009;87(2-3):203–212. doi:10.1016/j.eplepsyres.2009.09.002
Google Scholar | Crossref | Medline36. Adriaanse, SM, Binnewijzend, MAA, Ossenkoppele, R, et al. Widespread disruption of functional brain organization in early-onset Alzheimer’s disease. PLoS One. 2014;9(7):e102995.
Google Scholar | Crossref | Medline37. Chung, J, Yoo, K, Kim, E, Na, DL, Jeong, Y. Glucose metabolic brain networks in early-onset vs. Late-onset Alzheimer’s disease [Internet]. Front Aging Neurosci. 2016;8:159. Accessed December 21, 2017. https://www.frontiersin.org/articles/10.3389/fnagi.2016.00159/full
Google Scholar38. Gour, N, Felician, O, Didic, M, et al. Functional connectivity changes differ in early and late-onset Alzheimer’s disease. Hum Brain Mapp. 2014;35(7):2978–2994.
Google Scholar | Crossref | Medline | ISI39. Satoh, A, Iijima, KM. Roles of tau pathology in the Locus Coeruleus (LC) in age-associated pathophysiology and Alzheimer’s disease pathogenesis: potential strategies to protect the LC against aging. Brain Res. 2019;1702:17–28.
Google Scholar | Crossref | Medline40. Vlies, AE, van der, Koedam, ELGE, Pijnenburg, Ya L, Twisk, JWR, Scheltens, P, Flier, WM, van der. Most rapid cognitive decline in APOE ε4 negative Alzheimer’s disease with early onset. Psychol Med. 2009;39(11):1907–1911.
Google Scholar | Crossref | Medline41. Wilson, RS, Nag, S, Boyle, PA, et al. Neural reserve, neuronal density in the locus ceruleus, and cognitive decline. Neurology. 2013;80(13):1202–1208.
Google Scholar | Crossref | Medline42. Chalermpalanupap, T, Weinshenker, D, Rorabaugh, JM. Down but not out: the consequences of pretangle tau in the locus coeruleus [Internet]. Neural Plast. 2017. Accessed April 1, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605916/
Google Scholar43. Callahan, PM, Plagenhoef, MR, Blake, DT, Terry, AV. Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys. Neuropharmacology. 2019;155:65–75.
Google Scholar | Crossref | Medline44. Ni, HC, Shang, CY, Gau, SS, Lin, YJ, Huang, HC, Yang, LK. A head-to-head randomized clinical trial of methylphenidate and atomoxetine treatment for executive function in adults with attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2013;16(9):1959–1973.
Google Scholar | Crossref | Medline45. Mohs, RC, Shiovitz, TM, Tariot, PN, Porsteinsson, AP, Baker, KD, Feldman, PD. Atomoxetine augmentation of cholinesterase inhibitor therapy in patients with Alzheimer disease: 6-Month, randomized, double-blind, placebo-controlled, parallel-trial study. Am J Geriatr Psychiatry. 2009;17(9):752–759.
Google Scholar | Crossref | Medline46. Feinstein, DL, Kalinin, S, Braun, D. Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system. J Neurochem. 2016;139(S2):154–178.
Google Scholar47. Jacobs, HIL, Riphagen, JM, Ramakers, IHGB, Verhey, FRJ. Alzheimer’s disease pathology: pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms. Mol Psychiatry. 2019;26(3):897–906.
Google Scholar | Crossref | Medline48. Chalermpalanupap, T, Kinkead, B, Hu, WT, et al. Targeting norepinephrine in mild cognitive impairment and Alzheimer’s disease. Alzheimers Res Ther. 2013;5(2):21.
Google Scholar | Crossref | Medline49. Leanza, G, Gulino, R, Zorec, R. Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia [Internet]. Front Mol Neurosci. 2018;11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072880/
Google Scholar50. Betts, MJ, Kirilina, E, Otaduy, MCG, et al. Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases. Brain. 2019;142(9):2558–2571. doi:10.1093/brain/awz193
Google Scholar | Crossref | Medline51. Dahl, MJ, Mather, M, Düzel, S, et al. Higher rostral locus coeruleus integrity is associated with better memory performance in older adults. Nat Hum Behav 2019;3(11):1203–1214 doi:10.1038/s41562-019-0715-2
Google Scholar