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Erschienen in: Current Geriatrics Reports 2/2014

01.06.2014 | Neurology of Aging (KS Marder, Section Editor)

Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer’s Disease

verfasst von: Arjun V. Masurkar, D. P. Devanand

Erschienen in: Current Geriatrics Reports | Ausgabe 2/2014

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Abstract

Preclinical detection of Alzheimer’s disease is critical to determining at-risk individuals in order to improve patient and caregiver planning for their futures, and to identify individuals likely to benefit from treatment as advances in therapeutics develop over time. Identification of olfactory dysfunction at the preclinical and early stages of the disease is a potentially useful method to accomplish these goals. We first review basic olfactory circuitry. We then evaluate the evidence of pathophysiological change in the olfactory processing pathways during aging and Alzheimer’s disease in both human and animal models. We also review olfactory behavioral studies during these processes in both types of models. In doing so, we suggest hypotheses about the localization and mechanisms of olfactory dysfunction and identify important avenues for future work.
Literatur
1.
Zurück zum Zitat Doty RL. Olfactory dysfunction in Parkinson disease. Nat Rev Neurol. 2012;8:329–39.PubMed Doty RL. Olfactory dysfunction in Parkinson disease. Nat Rev Neurol. 2012;8:329–39.PubMed
2.
Zurück zum Zitat Shepherd GM, et al. Olfactory Bulb. In: Shepherd GM, editors. Synaptic Organization of the Brain. Oxford, New York, 2004. pp. 165-216. Shepherd GM, et al. Olfactory Bulb. In: Shepherd GM, editors. Synaptic Organization of the Brain. Oxford, New York, 2004. pp. 165-216.
3.
Zurück zum Zitat Doty RL. Office procedures for quantitative assessment of olfactory function. Am J Rhinol. 2007;21:460–73.PubMed Doty RL. Office procedures for quantitative assessment of olfactory function. Am J Rhinol. 2007;21:460–73.PubMed
4.
Zurück zum Zitat Paik SI, Lehman MN, Seiden AM, Duncan HJ, Smith DV. Human olfactory biopsy. The influence of age and receptor distribution. Arch Otolaryngol Head Neck Surg. 1992;118:731–8.PubMed Paik SI, Lehman MN, Seiden AM, Duncan HJ, Smith DV. Human olfactory biopsy. The influence of age and receptor distribution. Arch Otolaryngol Head Neck Surg. 1992;118:731–8.PubMed
5.
Zurück zum Zitat Rawson NE, Gomez G, Cowart BJ, Kriete A, Pribitkin E, Restrepo D. Age-associated loss of selectivity in human olfactory sensory neurons. Neurobiol Aging. 2012;33:1913–9.PubMedCentralPubMed Rawson NE, Gomez G, Cowart BJ, Kriete A, Pribitkin E, Restrepo D. Age-associated loss of selectivity in human olfactory sensory neurons. Neurobiol Aging. 2012;33:1913–9.PubMedCentralPubMed
6.
Zurück zum Zitat Maresh A, Rodriguez Gil D, Whitman MC, Greer CA. Principles of glomerular organization in the human olfactory bulb–implications for odor processing. PLoS One. 2008;3:e2640.PubMedCentralPubMed Maresh A, Rodriguez Gil D, Whitman MC, Greer CA. Principles of glomerular organization in the human olfactory bulb–implications for odor processing. PLoS One. 2008;3:e2640.PubMedCentralPubMed
7.
Zurück zum Zitat Meisami E, Mikhail L, Baim D, Bhatnagar KP. Human olfactory bulb: aging of glomeruli and mitral cells and a search for the accessory olfactory bulb. Ann N Y Acad Sci. 1998;855:708–15.PubMed Meisami E, Mikhail L, Baim D, Bhatnagar KP. Human olfactory bulb: aging of glomeruli and mitral cells and a search for the accessory olfactory bulb. Ann N Y Acad Sci. 1998;855:708–15.PubMed
8.
Zurück zum Zitat Morgan CD, Geisler MW, Covington JW, Polich J, Murphy C. Olfactory P3 in young and older adults. Psychophysiology. 1999;36:281–7.PubMed Morgan CD, Geisler MW, Covington JW, Polich J, Murphy C. Olfactory P3 in young and older adults. Psychophysiology. 1999;36:281–7.PubMed
9.
Zurück zum Zitat Yousem DM, Maldjian JA, Hummel T, Alsop DC, Geckle RJ, Kraut MA, et al. The effect of age on odor-stimulated functional MR imaging. AJNR Am J Neuroradiol. 1999;20:600–8.PubMed Yousem DM, Maldjian JA, Hummel T, Alsop DC, Geckle RJ, Kraut MA, et al. The effect of age on odor-stimulated functional MR imaging. AJNR Am J Neuroradiol. 1999;20:600–8.PubMed
10.
Zurück zum Zitat Suzuki Y, Critchley HD, Suckling J, Fukuda R, Williams SC, Andrew C, et al. Functional magnetic resonance imaging of odor identification: the effect of aging. J Gerontol A Biol Sci Med Sci. 2001;56:M756–760.PubMed Suzuki Y, Critchley HD, Suckling J, Fukuda R, Williams SC, Andrew C, et al. Functional magnetic resonance imaging of odor identification: the effect of aging. J Gerontol A Biol Sci Med Sci. 2001;56:M756–760.PubMed
11.
Zurück zum Zitat Kareken DA, Mosnik DM, Doty RL, Dzemidzic M, Hutchins GD. Functional anatomy of human odor sensation, discrimination, and identification in health and aging. Neuropsychology. 2003;17:482–95.PubMed Kareken DA, Mosnik DM, Doty RL, Dzemidzic M, Hutchins GD. Functional anatomy of human odor sensation, discrimination, and identification in health and aging. Neuropsychology. 2003;17:482–95.PubMed
12.
Zurück zum Zitat Cerf-Ducastel B, Murphy C. FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects. Brain Res. 2003;986:39–53.PubMed Cerf-Ducastel B, Murphy C. FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects. Brain Res. 2003;986:39–53.PubMed
13.
Zurück zum Zitat Wang J, Eslinger PJ, Smith MB, Yang QX. Functional magnetic resonance imaging study of human olfaction and normal aging. J Gerontol A Biol Sci Med Sci. 2005;60:510–4.PubMed Wang J, Eslinger PJ, Smith MB, Yang QX. Functional magnetic resonance imaging study of human olfaction and normal aging. J Gerontol A Biol Sci Med Sci. 2005;60:510–4.PubMed
14.
Zurück zum Zitat Mann DM, Tucker CM, Yates PO. Alzheimer's disease: an olfactory connection? Mech Ageing Dev. 1988;42:1–15.PubMed Mann DM, Tucker CM, Yates PO. Alzheimer's disease: an olfactory connection? Mech Ageing Dev. 1988;42:1–15.PubMed
15.
Zurück zum Zitat Reyes PF, Deems DA, Suarez MG. Olfactory-related changes in Alzheimer's disease: a quantitative neuropathologic study. Brain Res Bull. 1993;32:1–5.PubMed Reyes PF, Deems DA, Suarez MG. Olfactory-related changes in Alzheimer's disease: a quantitative neuropathologic study. Brain Res Bull. 1993;32:1–5.PubMed
16.
Zurück zum Zitat ter Laak HJ, Renkawek K, van Workum FP. The olfactory bulb in Alzheimer disease: a morphologic study of neuron loss, tangles, and senile plaques in relation to olfaction. Alzheimer Dis Assoc Disord. 1994;8:38–48.PubMed ter Laak HJ, Renkawek K, van Workum FP. The olfactory bulb in Alzheimer disease: a morphologic study of neuron loss, tangles, and senile plaques in relation to olfaction. Alzheimer Dis Assoc Disord. 1994;8:38–48.PubMed
17.
Zurück zum Zitat Mundinano IC, Caballero MC, Ordonez C, Hernandez M, DiCaudo C, Marcilla I, et al. Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders. Acta Neuropathol. 2011;122:61–74.PubMed Mundinano IC, Caballero MC, Ordonez C, Hernandez M, DiCaudo C, Marcilla I, et al. Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders. Acta Neuropathol. 2011;122:61–74.PubMed
18.
Zurück zum Zitat Cai Y, Xue ZQ, Zhang XM, Li MB, Wang H, Luo XG, et al. An age-related axon terminal pathology around the first olfactory relay that involves amyloidogenic protein overexpression without plaque formation. Neuroscience. 2012;215:160–73.PubMed Cai Y, Xue ZQ, Zhang XM, Li MB, Wang H, Luo XG, et al. An age-related axon terminal pathology around the first olfactory relay that involves amyloidogenic protein overexpression without plaque formation. Neuroscience. 2012;215:160–73.PubMed
19.
Zurück zum Zitat Esiri MM, Wilcock GK. The olfactory bulbs in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1984;47:56–60.PubMedCentralPubMed Esiri MM, Wilcock GK. The olfactory bulbs in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1984;47:56–60.PubMedCentralPubMed
20.
Zurück zum Zitat Ohm TG, Braak H. Olfactory bulb changes in Alzheimer's disease. Acta Neuropathol. 1987;73:365–9.PubMed Ohm TG, Braak H. Olfactory bulb changes in Alzheimer's disease. Acta Neuropathol. 1987;73:365–9.PubMed
21.
Zurück zum Zitat Loopuijt LD, Sebens JB. Loss of dopamine receptors in the olfactory bulb of patients with Alzheimer's disease. Brain Res. 1990;529:239–44.PubMed Loopuijt LD, Sebens JB. Loss of dopamine receptors in the olfactory bulb of patients with Alzheimer's disease. Brain Res. 1990;529:239–44.PubMed
22.
Zurück zum Zitat Hyman BT, Arriagada PV, Van Hoesen GW. Pathologic changes in the olfactory system in aging and Alzheimer's disease. Ann N Y Acad Sci. 1991;640:14–9.PubMed Hyman BT, Arriagada PV, Van Hoesen GW. Pathologic changes in the olfactory system in aging and Alzheimer's disease. Ann N Y Acad Sci. 1991;640:14–9.PubMed
23.
Zurück zum Zitat Struble RG, Clark HB. Olfactory bulb lesions in Alzheimer's disease. Neurobiol Aging. 1992;13:469–73.PubMed Struble RG, Clark HB. Olfactory bulb lesions in Alzheimer's disease. Neurobiol Aging. 1992;13:469–73.PubMed
24.
Zurück zum Zitat Attems J, Lintner F, Jellinger KA. Olfactory involvement in aging and Alzheimer's disease: an autopsy study. J Alzheimers Dis. 2005;7:149–57. discussion 173-180.PubMed Attems J, Lintner F, Jellinger KA. Olfactory involvement in aging and Alzheimer's disease: an autopsy study. J Alzheimers Dis. 2005;7:149–57. discussion 173-180.PubMed
25.
Zurück zum Zitat Kovacs T, Cairns NJ, Lantos PL. Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages. Neuroreport. 2001;12:285–8.PubMed Kovacs T, Cairns NJ, Lantos PL. Olfactory centres in Alzheimer's disease: olfactory bulb is involved in early Braak's stages. Neuroreport. 2001;12:285–8.PubMed
26.
Zurück zum Zitat Kovacs T, Cairns NJ, Lantos PL. beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease. Neuropathol Appl Neurobiol. 1999;25:481–91.PubMed Kovacs T, Cairns NJ, Lantos PL. beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease. Neuropathol Appl Neurobiol. 1999;25:481–91.PubMed
27.
Zurück zum Zitat Li W, Howard JD, Gottfried JA. Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer's disease. Brain. 2010;133:2714–26.PubMedCentralPubMed Li W, Howard JD, Gottfried JA. Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer's disease. Brain. 2010;133:2714–26.PubMedCentralPubMed
28.
Zurück zum Zitat Wang J, Eslinger PJ, Doty RL, Zimmerman EK, Grunfeld R, Sun X, et al. Olfactory deficit detected by fMRI in early Alzheimer's disease. Brain Res. 2010;1357:184–94.PubMedCentralPubMed Wang J, Eslinger PJ, Doty RL, Zimmerman EK, Grunfeld R, Sun X, et al. Olfactory deficit detected by fMRI in early Alzheimer's disease. Brain Res. 2010;1357:184–94.PubMedCentralPubMed
29.
Zurück zum Zitat Kareken DA, Doty RL, Moberg PJ, Mosnik D, Chen SH, Farlow MR, et al. Olfactory-evoked regional cerebral blood flow in Alzheimer's disease. Neuropsychology. 2001;15:18–29.PubMed Kareken DA, Doty RL, Moberg PJ, Mosnik D, Chen SH, Farlow MR, et al. Olfactory-evoked regional cerebral blood flow in Alzheimer's disease. Neuropsychology. 2001;15:18–29.PubMed
30.
Zurück zum Zitat Buchsbaum MS, Kesslak JP, Lynch G, Chui H, Wu J, Sicotte N, et al. Temporal and hippocampal metabolic rate during an olfactory memory task assessed by positron emission tomography in patients with dementia of the Alzheimer type and controls. Preliminary studies. Arch Gen Psychiatry. 1991;48:840–7.PubMed Buchsbaum MS, Kesslak JP, Lynch G, Chui H, Wu J, Sicotte N, et al. Temporal and hippocampal metabolic rate during an olfactory memory task assessed by positron emission tomography in patients with dementia of the Alzheimer type and controls. Preliminary studies. Arch Gen Psychiatry. 1991;48:840–7.PubMed
31.
Zurück zum Zitat Forster S, Vaitl A, Teipel SJ, Yakushev I, Mustafa M, la Fougere C, et al. Functional representation of olfactory impairment in early Alzheimer's disease. J Alzheimers Dis. 2010;22:581–91.PubMed Forster S, Vaitl A, Teipel SJ, Yakushev I, Mustafa M, la Fougere C, et al. Functional representation of olfactory impairment in early Alzheimer's disease. J Alzheimers Dis. 2010;22:581–91.PubMed
32.
Zurück zum Zitat Meisami E. A proposed relationship between increases in the number of olfactory receptor neurons, convergence ratio and sensitivity in the developing rat. Brain Res Dev Brain Res. 1989;46:9–19.PubMed Meisami E. A proposed relationship between increases in the number of olfactory receptor neurons, convergence ratio and sensitivity in the developing rat. Brain Res Dev Brain Res. 1989;46:9–19.PubMed
33.
Zurück zum Zitat Hinds JW, McNelly NA. Aging in the rat olfactory system: correlation of changes in the olfactory epithelium and olfactory bulb. J Comp Neurol. 1981;203:441–53.PubMed Hinds JW, McNelly NA. Aging in the rat olfactory system: correlation of changes in the olfactory epithelium and olfactory bulb. J Comp Neurol. 1981;203:441–53.PubMed
34.
Zurück zum Zitat Lee AC, Tian H, Grosmaitre X, Ma M. Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice. Chem Senses. 2009;34:695–703.PubMedCentralPubMed Lee AC, Tian H, Grosmaitre X, Ma M. Expression patterns of odorant receptors and response properties of olfactory sensory neurons in aged mice. Chem Senses. 2009;34:695–703.PubMedCentralPubMed
35.
Zurück zum Zitat Richard MB, Taylor SR, Greer CA. Age-induced disruption of selective olfactory bulb synaptic circuits. Proc Natl Acad Sci U S A. 2010;107:15613–8.PubMedCentralPubMed Richard MB, Taylor SR, Greer CA. Age-induced disruption of selective olfactory bulb synaptic circuits. Proc Natl Acad Sci U S A. 2010;107:15613–8.PubMedCentralPubMed
36.
Zurück zum Zitat Mirich JM, Williams NC, Berlau DJ, Brunjes PC. Comparative study of aging in the mouse olfactory bulb. J Comp Neurol. 2002;454:361–72.PubMed Mirich JM, Williams NC, Berlau DJ, Brunjes PC. Comparative study of aging in the mouse olfactory bulb. J Comp Neurol. 2002;454:361–72.PubMed
37.
Zurück zum Zitat Tropepe V, Craig CG, Morshead CM, van der Kooy D. Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci. 1997;17:7850–9.PubMed Tropepe V, Craig CG, Morshead CM, van der Kooy D. Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J Neurosci. 1997;17:7850–9.PubMed
38.
Zurück zum Zitat Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004;24:8354–65.PubMed Enwere E, Shingo T, Gregg C, Fujikawa H, Ohta S, Weiss S. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004;24:8354–65.PubMed
39.
Zurück zum Zitat Mobley AS, Bryant AK, Richard MB, Brann JH, Firestein SJ, Greer CA. Age-dependent regional changes in the rostral migratory stream. Neurobiol Aging. 2013;34:1873–81.PubMed Mobley AS, Bryant AK, Richard MB, Brann JH, Firestein SJ, Greer CA. Age-dependent regional changes in the rostral migratory stream. Neurobiol Aging. 2013;34:1873–81.PubMed
40.
Zurück zum Zitat Hinds JW, McNelly NA. Aging in the rat olfactory bulb: quantitative changes in mitral cell organelles and somato-dendritic synapses. J Comp Neurol. 1979;184:811–20.PubMed Hinds JW, McNelly NA. Aging in the rat olfactory bulb: quantitative changes in mitral cell organelles and somato-dendritic synapses. J Comp Neurol. 1979;184:811–20.PubMed
41.
Zurück zum Zitat Forbes WB. Aging-related morphological changes in the main olfactory bulb of the Fischer 344 rat. Neurobiol Aging. 1984;5:93–9.PubMed Forbes WB. Aging-related morphological changes in the main olfactory bulb of the Fischer 344 rat. Neurobiol Aging. 1984;5:93–9.PubMed
42.
Zurück zum Zitat Gocel J, Larson J. Evidence for loss of synaptic AMPA receptors in anterior piriform cortex of aged mice. Front Aging Neurosci. 2013;5:39.PubMedCentralPubMed Gocel J, Larson J. Evidence for loss of synaptic AMPA receptors in anterior piriform cortex of aged mice. Front Aging Neurosci. 2013;5:39.PubMedCentralPubMed
43.
Zurück zum Zitat Samson RD, Barnes CA. Impact of aging brain circuits on cognition. Eur J Neurosci. 2013;37:1903–15.PubMed Samson RD, Barnes CA. Impact of aging brain circuits on cognition. Eur J Neurosci. 2013;37:1903–15.PubMed
44.
Zurück zum Zitat Terranova JP, Perio A, Worms P, Le Fur G, Soubrie P. Social olfactory recognition in rodents: deterioration with age, cerebral ischaemia and septal lesion. Behav Pharmacol. 1994;5:90–8.PubMed Terranova JP, Perio A, Worms P, Le Fur G, Soubrie P. Social olfactory recognition in rodents: deterioration with age, cerebral ischaemia and septal lesion. Behav Pharmacol. 1994;5:90–8.PubMed
45.
Zurück zum Zitat Schoenbaum G, Setlow B, Saddoris MP, Gallagher M. Encoding changes in orbitofrontal cortex in reversal-impaired aged rats. J Neurophysiol. 2006;95:1509–17.PubMedCentralPubMed Schoenbaum G, Setlow B, Saddoris MP, Gallagher M. Encoding changes in orbitofrontal cortex in reversal-impaired aged rats. J Neurophysiol. 2006;95:1509–17.PubMedCentralPubMed
46.
Zurück zum Zitat Guerin D, Sacquet J, Mandairon N, Jourdan F, Didier A. Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice. Neurobiol Aging. 2009;30:272–83.PubMed Guerin D, Sacquet J, Mandairon N, Jourdan F, Didier A. Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice. Neurobiol Aging. 2009;30:272–83.PubMed
47.
Zurück zum Zitat Kameshima N, Nanjou T, Fukuhara T, Yanagisawa D, Tooyama I. Correlation of Abeta deposition in the nasal cavity with the formation of senile plaques in the brain of a transgenic mouse model of Alzheimer's disease. Neurosci Lett. 2012;513:166–9.PubMed Kameshima N, Nanjou T, Fukuhara T, Yanagisawa D, Tooyama I. Correlation of Abeta deposition in the nasal cavity with the formation of senile plaques in the brain of a transgenic mouse model of Alzheimer's disease. Neurosci Lett. 2012;513:166–9.PubMed
48.
Zurück zum Zitat Wu N, Rao X, Gao Y, Wang J, Xu F. Amyloid-beta deposition and olfactory dysfunction in an Alzheimer's disease model. J Alzheimers Dis. 2013;37:699–712.PubMed Wu N, Rao X, Gao Y, Wang J, Xu F. Amyloid-beta deposition and olfactory dysfunction in an Alzheimer's disease model. J Alzheimers Dis. 2013;37:699–712.PubMed
49.
Zurück zum Zitat Cheng N, Cai H, Belluscio L. In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function. J Neurosci. 2011;31:13699–704.PubMedCentralPubMed Cheng N, Cai H, Belluscio L. In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function. J Neurosci. 2011;31:13699–704.PubMedCentralPubMed
50.•
Zurück zum Zitat Cao L, Schrank BR, Rodriguez S, Benz EG, Moulia TW, Rickenbacher GT, et al. Abeta alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. Nat Commun. 2012;3:1009. By using a mouse model in which human APP is expressed only in olfactory receptor neurons, the authors demonstrate disruption of the peripheral olfactory circuits in the absence of Aβ plaque.PubMedCentralPubMed Cao L, Schrank BR, Rodriguez S, Benz EG, Moulia TW, Rickenbacher GT, et al. Abeta alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. Nat Commun. 2012;3:1009. By using a mouse model in which human APP is expressed only in olfactory receptor neurons, the authors demonstrate disruption of the peripheral olfactory circuits in the absence of Aβ plaque.PubMedCentralPubMed
51.
Zurück zum Zitat Cheng N, Bai L, Steuer E, Belluscio L. Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model. J Neurosci. 2013;33:12208–17.PubMedCentralPubMed Cheng N, Bai L, Steuer E, Belluscio L. Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model. J Neurosci. 2013;33:12208–17.PubMedCentralPubMed
52.
Zurück zum Zitat Rockenstein E, Mallory M, Mante M, Sisk A, Masliaha E. Early formation of mature amyloid-beta protein deposits in a mutant APP transgenic model depends on levels of Abeta (1-42). J Neurosci Res. 2001;66:573–82.PubMed Rockenstein E, Mallory M, Mante M, Sisk A, Masliaha E. Early formation of mature amyloid-beta protein deposits in a mutant APP transgenic model depends on levels of Abeta (1-42). J Neurosci Res. 2001;66:573–82.PubMed
53.
Zurück zum Zitat Lehman EJ, Kulnane LS, Lamb BT. Alterations in beta-amyloid production and deposition in brain regions of two transgenic models. Neurobiol Aging. 2003;24:645–53.PubMed Lehman EJ, Kulnane LS, Lamb BT. Alterations in beta-amyloid production and deposition in brain regions of two transgenic models. Neurobiol Aging. 2003;24:645–53.PubMed
54.•
Zurück zum Zitat Cassano T, Romano A, Macheda T, Colangeli R, Cimmino CS, Petrella A, et al. Olfactory memory is impaired in a triple transgenic model of Alzheimer disease. Behav Brain Res. 2011;224:408–12. Most animal models of Alzheimer’s disease utilize amyloidogenic genes. Here, odor-based memory testing was performed in a transgenic mouse expressing both Aβ and tau pathology. Severe deficits were found, but pathology was limited to higher order olfactory centers and not the olfactory bulb.PubMed Cassano T, Romano A, Macheda T, Colangeli R, Cimmino CS, Petrella A, et al. Olfactory memory is impaired in a triple transgenic model of Alzheimer disease. Behav Brain Res. 2011;224:408–12. Most animal models of Alzheimer’s disease utilize amyloidogenic genes. Here, odor-based memory testing was performed in a transgenic mouse expressing both Aβ and tau pathology. Severe deficits were found, but pathology was limited to higher order olfactory centers and not the olfactory bulb.PubMed
55.
Zurück zum Zitat Wesson DW, Levy E, Nixon RA, Wilson DA. Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model. J Neurosci. 2010;30:505–14.PubMedCentralPubMed Wesson DW, Levy E, Nixon RA, Wilson DA. Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model. J Neurosci. 2010;30:505–14.PubMedCentralPubMed
56.
Zurück zum Zitat Saiz-Sanchez D, De La Rosa-Prieto C, Ubeda-Banon I, Martinez-Marcos A. Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease. Anat Rec (Hoboken). 2013;296:1413–23. Saiz-Sanchez D, De La Rosa-Prieto C, Ubeda-Banon I, Martinez-Marcos A. Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease. Anat Rec (Hoboken). 2013;296:1413–23.
57.
Zurück zum Zitat Haughey NJ, Liu D, Nath A, Borchard AC, Mattson MP. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. Neuromol Med. 2002;1:125–35. Haughey NJ, Liu D, Nath A, Borchard AC, Mattson MP. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer's disease. Neuromol Med. 2002;1:125–35.
58.
Zurück zum Zitat Demars M, Hu YS, Gadadhar A, Lazarov O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice. J Neurosci Res. 2010;88:2103–17.PubMedCentralPubMed Demars M, Hu YS, Gadadhar A, Lazarov O. Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice. J Neurosci Res. 2010;88:2103–17.PubMedCentralPubMed
59.
Zurück zum Zitat Sotthibundhu A, Li QX, Thangnipon W, Coulson EJ. Abeta(1-42) stimulates adult SVZ neurogenesis through the p75 neurotrophin receptor. Neurobiol Aging. 2009;30:1975–85.PubMed Sotthibundhu A, Li QX, Thangnipon W, Coulson EJ. Abeta(1-42) stimulates adult SVZ neurogenesis through the p75 neurotrophin receptor. Neurobiol Aging. 2009;30:1975–85.PubMed
60.
Zurück zum Zitat Zhang C, McNeil E, Dressler L, Siman R. Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease. Exp Neurol. 2007;204:77–87.PubMedCentralPubMed Zhang C, McNeil E, Dressler L, Siman R. Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease. Exp Neurol. 2007;204:77–87.PubMedCentralPubMed
61.
Zurück zum Zitat Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001;293:1487–91.PubMed Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001;293:1487–91.PubMed
62.
Zurück zum Zitat Kim TK, Lee JE, Park SK, Lee KW, Seo JS, Im JY, et al. Analysis of differential plaque depositions in the brains of Tg2576 and Tg-APPswe/PS1dE9 transgenic mouse models of Alzheimer disease. Exp Mol Med. 2012;44:492–502.PubMedCentralPubMed Kim TK, Lee JE, Park SK, Lee KW, Seo JS, Im JY, et al. Analysis of differential plaque depositions in the brains of Tg2576 and Tg-APPswe/PS1dE9 transgenic mouse models of Alzheimer disease. Exp Mol Med. 2012;44:492–502.PubMedCentralPubMed
63.
Zurück zum Zitat Saiz-Sanchez D, Ubeda-Banon I, De la Rosa-Prieto C, Martinez-Marcos A. Differential expression of interneuron populations and correlation with amyloid-beta deposition in the olfactory cortex of an AbetaPP/PS1 transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2012;31:113–29.PubMed Saiz-Sanchez D, Ubeda-Banon I, De la Rosa-Prieto C, Martinez-Marcos A. Differential expression of interneuron populations and correlation with amyloid-beta deposition in the olfactory cortex of an AbetaPP/PS1 transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2012;31:113–29.PubMed
64.•
Zurück zum Zitat Wesson DW, Borkowski AH, Landreth GE, Nixon RA, Levy E, Wilson DA. Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer's beta-amyloidosis mouse model. J Neurosci. 2011;31:15962–71. The investigators used the Tg2576 Alzheimer mouse to demonstrate that aberrant electrical activity in the OB coincides with amyloid in that region, but prior to the behavioral deficits that coincide with piriform cortex dysfunction.PubMedCentralPubMed Wesson DW, Borkowski AH, Landreth GE, Nixon RA, Levy E, Wilson DA. Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer's beta-amyloidosis mouse model. J Neurosci. 2011;31:15962–71. The investigators used the Tg2576 Alzheimer mouse to demonstrate that aberrant electrical activity in the OB coincides with amyloid in that region, but prior to the behavioral deficits that coincide with piriform cortex dysfunction.PubMedCentralPubMed
65.
Zurück zum Zitat Girard SD, Baranger K, Gauthier C, Jacquet M, Bernard A, Escoffier G, et al. Evidence for early cognitive impairment related to frontal cortex in the 5XFAD mouse model of Alzheimer's disease. J Alzheimers Dis. 2013;33:781–96.PubMed Girard SD, Baranger K, Gauthier C, Jacquet M, Bernard A, Escoffier G, et al. Evidence for early cognitive impairment related to frontal cortex in the 5XFAD mouse model of Alzheimer's disease. J Alzheimers Dis. 2013;33:781–96.PubMed
66.
Zurück zum Zitat Eibenstein A, Fioretti AB, Simaskou MN, Sucapane P, Mearelli S, Mina C, et al. Olfactory screening test in mild cognitive impairment. Neurol Sci. 2005;26:156–60.PubMed Eibenstein A, Fioretti AB, Simaskou MN, Sucapane P, Mearelli S, Mina C, et al. Olfactory screening test in mild cognitive impairment. Neurol Sci. 2005;26:156–60.PubMed
67.
Zurück zum Zitat Djordjevic J, Jones-Gotman M, De Sousa K, Chertkow H. Olfaction in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2008;29:693–706.PubMed Djordjevic J, Jones-Gotman M, De Sousa K, Chertkow H. Olfaction in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2008;29:693–706.PubMed
68.
Zurück zum Zitat Laakso MP, Tervo S, Hanninen T, Vanhanen M, Hallikainen M, Soininen H. Olfactory identification in non-demented elderly population and in mild cognitive impairment: a comparison of performance in clinical odor identification versus Boston Naming Test. J Neural Transm. 2009;116:891–5.PubMed Laakso MP, Tervo S, Hanninen T, Vanhanen M, Hallikainen M, Soininen H. Olfactory identification in non-demented elderly population and in mild cognitive impairment: a comparison of performance in clinical odor identification versus Boston Naming Test. J Neural Transm. 2009;116:891–5.PubMed
69.
Zurück zum Zitat Bahar-Fuchs A, Chetelat G, Villemagne VL, Moss S, Pike K, Masters CL, et al. Olfactory deficits and amyloid-beta burden in Alzheimer's disease, mild cognitive impairment, and healthy aging: a PiB PET study. J Alzheimers Dis. 2010;22:1081–7.PubMed Bahar-Fuchs A, Chetelat G, Villemagne VL, Moss S, Pike K, Masters CL, et al. Olfactory deficits and amyloid-beta burden in Alzheimer's disease, mild cognitive impairment, and healthy aging: a PiB PET study. J Alzheimers Dis. 2010;22:1081–7.PubMed
70.
Zurück zum Zitat Velayudhan L, Pritchard M, Powell JF, Proitsi P, Lovestone S. Smell identification function as a severity and progression marker in Alzheimer's disease. Int Psychogeriatr. 2013;25:1157–66. This group investigated whether olfactory decline correlated with cognitive progression and illness severity in AD patients. AD patients with recent rapid cognitive progression were found to be associated with rapid olfactory decline at 3 months follow-up, whereas non-rapid cognitive progression was associated with slow olfactory decline. Rapid olfactory decline with higher olfactory dysfunction correlated with high illness severity.PubMed Velayudhan L, Pritchard M, Powell JF, Proitsi P, Lovestone S. Smell identification function as a severity and progression marker in Alzheimer's disease. Int Psychogeriatr. 2013;25:1157–66. This group investigated whether olfactory decline correlated with cognitive progression and illness severity in AD patients. AD patients with recent rapid cognitive progression were found to be associated with rapid olfactory decline at 3 months follow-up, whereas non-rapid cognitive progression was associated with slow olfactory decline. Rapid olfactory decline with higher olfactory dysfunction correlated with high illness severity.PubMed
71.
Zurück zum Zitat Westervelt HJ, Bruce JM, Coon WG, Tremont G. Odor identification in mild cognitive impairment subtypes. J Clin Exp Neuropsychol. 2008;30:151–6.PubMed Westervelt HJ, Bruce JM, Coon WG, Tremont G. Odor identification in mild cognitive impairment subtypes. J Clin Exp Neuropsychol. 2008;30:151–6.PubMed
72.
Zurück zum Zitat Lehrner J, Pusswald G, Gleiss A, Auff E, Dal-Bianco P. Odor identification and self-reported olfactory functioning in patients with subtypes of mild cognitive impairment. Clin Neuropsychol. 2009;23:818–30.PubMed Lehrner J, Pusswald G, Gleiss A, Auff E, Dal-Bianco P. Odor identification and self-reported olfactory functioning in patients with subtypes of mild cognitive impairment. Clin Neuropsychol. 2009;23:818–30.PubMed
73.
Zurück zum Zitat Devanand DP, Tabert MH, Cuasay K, Manly JJ, Schupf N, Brickman AM, et al. Olfactory identification deficits and MCI in a multi-ethnic elderly community sample. Neurobiol Aging. 2010;31:1593–600.PubMedCentralPubMed Devanand DP, Tabert MH, Cuasay K, Manly JJ, Schupf N, Brickman AM, et al. Olfactory identification deficits and MCI in a multi-ethnic elderly community sample. Neurobiol Aging. 2010;31:1593–600.PubMedCentralPubMed
74.
Zurück zum Zitat Bacon AW, Bondi MW, Salmon DP, Murphy C. Very early changes in olfactory functioning due to Alzheimer's disease and the role of apolipoprotein E in olfaction. Ann N Y Acad Sci. 1998;855:723–31.PubMed Bacon AW, Bondi MW, Salmon DP, Murphy C. Very early changes in olfactory functioning due to Alzheimer's disease and the role of apolipoprotein E in olfaction. Ann N Y Acad Sci. 1998;855:723–31.PubMed
75.
Zurück zum Zitat Graves AB, Bowen JD, Rajaram L, McCormick WC, McCurry SM, Schellenberg GD, et al. Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status. Neurology. 1999;53:1480–7.PubMed Graves AB, Bowen JD, Rajaram L, McCormick WC, McCurry SM, Schellenberg GD, et al. Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status. Neurology. 1999;53:1480–7.PubMed
76.
Zurück zum Zitat Devanand DP, Michaels-Marston KS, Liu X, Pelton GH, Padilla M, Marder K, et al. Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up. Am J Psychiatry. 2000;157:1399–405.PubMed Devanand DP, Michaels-Marston KS, Liu X, Pelton GH, Padilla M, Marder K, et al. Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up. Am J Psychiatry. 2000;157:1399–405.PubMed
77.
Zurück zum Zitat Royall DR, Chiodo LK, Polk MS, Jaramillo CJ. Severe dysosmia is specifically associated with Alzheimer-like memory deficits in nondemented elderly retirees. Neuroepidemiology. 2002;21:68–73.PubMed Royall DR, Chiodo LK, Polk MS, Jaramillo CJ. Severe dysosmia is specifically associated with Alzheimer-like memory deficits in nondemented elderly retirees. Neuroepidemiology. 2002;21:68–73.PubMed
78.
Zurück zum Zitat Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, et al. A 10-item smell identification scale related to risk for Alzheimer's disease. Ann Neurol. 2005;58:155–60.PubMed Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, et al. A 10-item smell identification scale related to risk for Alzheimer's disease. Ann Neurol. 2005;58:155–60.PubMed
79.
Zurück zum Zitat Wilson RS, Arnold SE, Schneider JA, Tang Y, Bennett DA. The relationship between cerebral Alzheimer's disease pathology and odour identification in old age. J Neurol Neurosurg Psychiatry. 2007;78:30–5.PubMedCentralPubMed Wilson RS, Arnold SE, Schneider JA, Tang Y, Bennett DA. The relationship between cerebral Alzheimer's disease pathology and odour identification in old age. J Neurol Neurosurg Psychiatry. 2007;78:30–5.PubMedCentralPubMed
80.
Zurück zum Zitat Devanand DP, Liu X, Tabert MH, Pradhaban G, Cuasay K, Bell K, et al. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry. 2008;64:871–9.PubMedCentralPubMed Devanand DP, Liu X, Tabert MH, Pradhaban G, Cuasay K, Bell K, et al. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry. 2008;64:871–9.PubMedCentralPubMed
81.
Zurück zum Zitat Schubert CR, Carmichael LL, Murphy C, Klein BE, Klein R, Cruickshanks KJ. Olfaction and the 5-year incidence of cognitive impairment in an epidemiological study of older adults. J Am Geriatr Soc. 2008;56:1517–21.PubMedCentralPubMed Schubert CR, Carmichael LL, Murphy C, Klein BE, Klein R, Cruickshanks KJ. Olfaction and the 5-year incidence of cognitive impairment in an epidemiological study of older adults. J Am Geriatr Soc. 2008;56:1517–21.PubMedCentralPubMed
82.•
Zurück zum Zitat Conti MZ, Vicini-Chilovi B, Riva M, Zanetti M, Liberini P, Padovani A, et al. Odor identification deficit predicts clinical conversion from mild cognitive impairment to dementia due to Alzheimer's disease. Arch Clin Neuropsychol. 2013;28:391–9. This article assessed whether baseline olfactory deficit in MCI patients predicted conversion to dementia. At two years followup, 47 % of dysosmic MCI patients converted to dementia compared to 11 % of the normosmics, with an odds ratio for conversion of 5.1, independent of baseline MMSE.PubMed Conti MZ, Vicini-Chilovi B, Riva M, Zanetti M, Liberini P, Padovani A, et al. Odor identification deficit predicts clinical conversion from mild cognitive impairment to dementia due to Alzheimer's disease. Arch Clin Neuropsychol. 2013;28:391–9. This article assessed whether baseline olfactory deficit in MCI patients predicted conversion to dementia. At two years followup, 47 % of dysosmic MCI patients converted to dementia compared to 11 % of the normosmics, with an odds ratio for conversion of 5.1, independent of baseline MMSE.PubMed
83.
Zurück zum Zitat Murphy C, Jernigan TL, Fennema-Notestine C. Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study. J Int Neuropsychol Soc. 2003;9:459–71.PubMed Murphy C, Jernigan TL, Fennema-Notestine C. Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study. J Int Neuropsychol Soc. 2003;9:459–71.PubMed
84.
Zurück zum Zitat Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: changes with age. Science. 1984;226:1441–3.PubMed Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: changes with age. Science. 1984;226:1441–3.PubMed
85.
Zurück zum Zitat Wilson RS, Schneider JA, Arnold SE, Tang Y, Boyle PA, Bennett DA. Olfactory identification and incidence of mild cognitive impairment in older age. Arch Gen Psychiatry. 2007;64:802–8.PubMed Wilson RS, Schneider JA, Arnold SE, Tang Y, Boyle PA, Bennett DA. Olfactory identification and incidence of mild cognitive impairment in older age. Arch Gen Psychiatry. 2007;64:802–8.PubMed
86.
Zurück zum Zitat Bacon Moore AS, Paulsen JS, Murphy C. A test of odor fluency in patients with Alzheimer's and Huntington's disease. J Clin Exp Neuropsychol. 1999;21:341–51.PubMed Bacon Moore AS, Paulsen JS, Murphy C. A test of odor fluency in patients with Alzheimer's and Huntington's disease. J Clin Exp Neuropsychol. 1999;21:341–51.PubMed
87.
Zurück zum Zitat Kraemer S, Apfelbach R. Olfactory sensitivity, learning and cognition in young adult and aged male Wistar rats. Physiol Behav. 2004;81:435–42.PubMed Kraemer S, Apfelbach R. Olfactory sensitivity, learning and cognition in young adult and aged male Wistar rats. Physiol Behav. 2004;81:435–42.PubMed
88.
Zurück zum Zitat Patel RC, Larson J. Impaired olfactory discrimination learning and decreased olfactory sensitivity in aged C57Bl/6 mice. Neurobiol Aging. 2009;30:829–37.PubMedCentralPubMed Patel RC, Larson J. Impaired olfactory discrimination learning and decreased olfactory sensitivity in aged C57Bl/6 mice. Neurobiol Aging. 2009;30:829–37.PubMedCentralPubMed
89.
Zurück zum Zitat LaSarge CL, Montgomery KS, Tucker C, Slaton GS, Griffith WH, Setlow B, et al. Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats. Neurobiol Aging. 2007;28:928–36.PubMed LaSarge CL, Montgomery KS, Tucker C, Slaton GS, Griffith WH, Setlow B, et al. Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats. Neurobiol Aging. 2007;28:928–36.PubMed
90.
Zurück zum Zitat Prediger RD, De-Mello N, Takahashi RN. Pilocarpine improves olfactory discrimination and social recognition memory deficits in 24 month-old rats. Eur J Pharmacol. 2006;531:176–82.PubMed Prediger RD, De-Mello N, Takahashi RN. Pilocarpine improves olfactory discrimination and social recognition memory deficits in 24 month-old rats. Eur J Pharmacol. 2006;531:176–82.PubMed
91.
Zurück zum Zitat Luu TT, Pirogovsky E, Gilbert PE. Age-related changes in contextual associative learning. Neurobiol Learn Mem. 2008;89:81–5.PubMedCentralPubMed Luu TT, Pirogovsky E, Gilbert PE. Age-related changes in contextual associative learning. Neurobiol Learn Mem. 2008;89:81–5.PubMedCentralPubMed
92.
Zurück zum Zitat Guan X, Dluzen DE. Age related changes of social memory/recognition in male Fischer 344 rats. Behav Brain Res. 1994;61:87–90.PubMed Guan X, Dluzen DE. Age related changes of social memory/recognition in male Fischer 344 rats. Behav Brain Res. 1994;61:87–90.PubMed
93.
Zurück zum Zitat Roman FS, Alescio-Lautier B, Soumireu-Mourat B. Age-related learning and memory deficits in odor-reward association in rats. Neurobiol Aging. 1996;17:31–40.PubMed Roman FS, Alescio-Lautier B, Soumireu-Mourat B. Age-related learning and memory deficits in odor-reward association in rats. Neurobiol Aging. 1996;17:31–40.PubMed
94.
Zurück zum Zitat Phillips M, Boman E, Osterman H, Willhite D, Laska M. Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice–a longitudinal study. PLoS One. 2011;6:e19567.PubMedCentralPubMed Phillips M, Boman E, Osterman H, Willhite D, Laska M. Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice–a longitudinal study. PLoS One. 2011;6:e19567.PubMedCentralPubMed
95.
Zurück zum Zitat Montgomery KS, Simmons RK, Edwards 3rd G, Nicolle MM, Gluck MA, Myers CE, et al. Novel age-dependent learning deficits in a mouse model of Alzheimer's disease: implications for translational research. Neurobiol Aging. 2011;32:1273–85.PubMed Montgomery KS, Simmons RK, Edwards 3rd G, Nicolle MM, Gluck MA, Myers CE, et al. Novel age-dependent learning deficits in a mouse model of Alzheimer's disease: implications for translational research. Neurobiol Aging. 2011;32:1273–85.PubMed
96.
Zurück zum Zitat Young JW, Sharkey J, Finlayson K. Progressive impairment in olfactory working memory in a mouse model of Mild Cognitive Impairment. Neurobiol Aging. 2009;30:1430–43.PubMed Young JW, Sharkey J, Finlayson K. Progressive impairment in olfactory working memory in a mouse model of Mild Cognitive Impairment. Neurobiol Aging. 2009;30:1430–43.PubMed
97.
Zurück zum Zitat Deacon RM, Koros E, Bornemann KD, Rawlins JN. Aged Tg2576 mice are impaired on social memory and open field habituation tests. Behav Brain Res. 2009;197:466–8.PubMed Deacon RM, Koros E, Bornemann KD, Rawlins JN. Aged Tg2576 mice are impaired on social memory and open field habituation tests. Behav Brain Res. 2009;197:466–8.PubMed
98.
Zurück zum Zitat Rey NL, Jardanhazi-Kurutz D, Terwel D, Kummer MP, Jourdan F, Didier A, et al. Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice. Neurobiol Aging. 2012;33(426):e421–411. Rey NL, Jardanhazi-Kurutz D, Terwel D, Kummer MP, Jourdan F, Didier A, et al. Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice. Neurobiol Aging. 2012;33(426):e421–411.
99.
Zurück zum Zitat Murphy C, Bacon AW, Bondi MW, Salmon DP. Apolipoprotein E status is associated with odor identification deficits in nondemented older persons. Ann N Y Acad Sci. 1998;855:744–50.PubMed Murphy C, Bacon AW, Bondi MW, Salmon DP. Apolipoprotein E status is associated with odor identification deficits in nondemented older persons. Ann N Y Acad Sci. 1998;855:744–50.PubMed
100.
Zurück zum Zitat Olofsson JK, Nordin S, Wiens S, Hedner M, Nilsson LG, Larsson M. Odor identification impairment in carriers of ApoE-varepsilon4 is independent of clinical dementia. Neurobiol Aging. 2010;31:567–77.PubMed Olofsson JK, Nordin S, Wiens S, Hedner M, Nilsson LG, Larsson M. Odor identification impairment in carriers of ApoE-varepsilon4 is independent of clinical dementia. Neurobiol Aging. 2010;31:567–77.PubMed
101.
Zurück zum Zitat Doty RL, Petersen I, Mensah N, Christensen K. Genetic and environmental influences on odor identification ability in the very old. Psychol Aging. 2011;26:864–71.PubMedCentralPubMed Doty RL, Petersen I, Mensah N, Christensen K. Genetic and environmental influences on odor identification ability in the very old. Psychol Aging. 2011;26:864–71.PubMedCentralPubMed
102.
Zurück zum Zitat Nee LE, Lippa CF. Inherited Alzheimer's disease PS-1 olfactory function: a 10-year follow-up study. Am J Alzheimers Dis Other Demen. 2001;16:83–4.PubMed Nee LE, Lippa CF. Inherited Alzheimer's disease PS-1 olfactory function: a 10-year follow-up study. Am J Alzheimers Dis Other Demen. 2001;16:83–4.PubMed
Metadaten
Titel
Olfactory Dysfunction in the Elderly: Basic Circuitry and Alterations with Normal Aging and Alzheimer’s Disease
verfasst von
Arjun V. Masurkar
D. P. Devanand
Publikationsdatum
01.06.2014
Verlag
Springer US
Erschienen in
Current Geriatrics Reports / Ausgabe 2/2014
Elektronische ISSN: 2196-7865
DOI
https://doi.org/10.1007/s13670-014-0080-y

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