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Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: A structural MRI study

  • Murphy Claire (a1) (a2), Jernigan Terry L. (a3) (a2) and Fennema-Notestine Christine (a3) (a2)

Abstract

The very high sensitivity and specificity of odor identification tasks in discriminating between Alzheimer's patients and normals suggests that they reflect the presence of underlying neuropathology. Significant neuropathological changes are seen in areas critical to processing olfactory information, even in the early stages of Alzheimer's disease (AD). The current study was designed to investigate whether performance on olfactory tasks (odor threshold and odor identification) was related to volumetric MRI measures of mesial temporal areas central to olfactory information processing and important in the neuropathology of AD. Participants were 8 male and 5 female patients with probable AD, and 10 male and 12 female normal age-matched controls, diagnosed at the UCSD Alzheimer's Disease Research Center. The study investigated correlations between volumetric measures of hippocampus, the parahippocampal gyrus and the amygdala, and the psychophysical measures of olfactory function. Robust relationships were observed between mesial temporal lobe volumes and olfactory functional measures. The finding of a strong relationship between left hippocampal volume and performance on the odor identification task (r = .85) is compatible with a left-hemisphere superiority for verbally mediated olfactory tasks. The findings suggest a neural substrate for the breakdown in functional performance on verbally mediated odor identification tasks in Alzheimer's disease and suggest the utility of quantitative MRI measures and psychophysical performance in the assessment of AD. These results support the potential clinical utility of inclusion of odor identification tests in diagnostic batteries for detecting AD. (JINS, 2003, 9, 459–471.)

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Corresponding author

Reprint requests to: Dr. Claire Murphy, SDSU/UCSD Joint Doctoral Program, 6363 Alvarado Ct., Suite 101, San Diego, CA 92120-4913. E-mail: cmurphy@sunstroke.sdsu.edu

References

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American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (Rev. 3rd ed.). Washington, DC: Author.
Andreasen, N.C., Arndt, S., Swayze, V., Cizadlo, T., Flaum, M., O'Leary, D., Ehrhardt, J.C., & Yuh, W.T. (1994). Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science, 266, 294–298.10.1126/science.7939669
Bacon, A.W., Bondi, M.W., Salmon, D.P., & Murphy, C. (1998). Very early changes in olfactory functioning due to Alzheimer's disease and the role of apolipoprotein E in olfaction. Annals of the New York Academy of Sciences, 855, 723–731.10.1111/j.1749-6632.1998.tb10651.x
Bacon, A.W., Paulsen, J.S., & Murphy, C. (1999). A test of odor fluency in patients with Alzheimer's disease and Huntington's Chorea. Journal of Clinical and Experimental Neuropsychology, 21, 341–351.
Biella, G. & de Curtis, M. (2000). Olfactory inputs activate the medial entorhinal cortex via the hippocampus. Journal of Neurophysiology, 83, 1924–1931.10.1152/jn.2000.83.4.1924
Braak, H., Braak, E. (1992). The human entorhinal cortex: Normal morphology and lamina-specific pathology in various diseases. Neuroscience Research, 15, 6–31.10.1016/0168-0102(92)90014-4
Braak, H., Braak, E. (1994). Morphological criteria for the recognition of Alzheimer's disease and the distribution pattern of cortical changes related to this disorder. Neurobiology of Aging, 15, 355–356.10.1016/0197-4580(94)90032-9
Braak, H., Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18, 351–357.10.1016/S0197-4580(97)00056-0
Cahn, D., Sullivan, E.V., Shear, P.K., Marsh, L., Fama, R., Lim, K.L., Yesavage, J.A., Tinklenberg, J.R., & Pfefferbaum, A. (1998). Structural MRI correlates of recognition memory in Alzheimer's disease. Journal of the International Neuropsychological Society, 4, 106–114.10.1017/S1355617798001064
Carmichael, S.T., Clugnet, M.C., & Price, J.L. (1994). Central olfactory connections in the macaque monkey. Journal of Comparative Neurology, 346, 403–434.
Cerf-Ducastel, B. & Murphy, C. (2001). FMRI activation in response to odorants orally delivered in aqueous solution. Chemical Senses, 26, 625–637.
Cohen, N.J., Ryan, J., Hunt, C., Romine, L., Wszalek, T., & Nash, C. (1999). Hippocampal system and declarative (relational) memory: Summarizing the data from functional neuroimaging studies. Hippocampus, 9, 83–98.
Delis, D.C., Kramer, J.H., Kaplan, E., & Ober, B.A. (1987). The California Verbal Learning Test. New York: The Psychological Corporation.
Deweer, B., Lehericy, S., Pillon, B., Baulac, M., Chiras, J., Marsault, C., Agid, & Y., Dubois. B. (1995). Memory disorders in probable Alzheimer's disease: The role of hippocampal atrophy as shown with MRI. Journal of Neurology, Neurosurgery, and Psychiatry, 58, 590–597.
Doty, R.L., Reyes, P.F., & Gregor, T. (1987). Presence of both identification and detection deficits in Alzheimer's disease. Brain Research Bulletin, 18, 597–600.
Doty, R.L., Shaman, P., & Dann, M. (1984). Development of the University of Pennsylvania Smell Identification Test: A standardized microencapsulated test of olfactory function. Physiology and Behavior, 32, 489–502.10.1016/0031-9384(84)90269-5
Eichenbaum, H. (1998). Using olfaction to study memory. Annals of the New York Academy of Sciences, 855, 657–669.10.1111/j.1749-6632.1998.tb10642.x
Ekman, G., Berglund, B., Berglund, U., & Lindvall, T. (1967). Perceived intensity of odor as a function of time of adaptation. Scandinavian Journal of Psychology, 8, 177–186.
Eskenazi, B., Cain, W.S., Novelly, R.A., & Mattson, R. (1986). Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia, 24, 553–562.10.1016/0028-3932(86)90099-0
Fama, R., Sullivan, E.V., Shear, P.K., Marsh, L., Yesavage, J.A., Tinklenberg, J.R., Lim, K.O., & Pfefferbaum, A. (1997). Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease. Archives of Neurology, 43, 719–728.
Fennema-Notestine, C., Archibald, S.L., Jernigan, T.L., & Thal, L. (1997). Quantitative MRI in Alzheimer's disease and controls with and without the apolipoprotein E e4 allele. Society for Neuroscience Abstracts, 23, 2173.
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini-Mental State”: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.
Hubbard, B.M. & Anderson, J.M. (1981). A quantitative study of cerebral atrophy in old age and senile dementia. Journal of the Neurological Sciences, 50, 135–145.10.1016/0022-510X(81)90048-4
Jack, C.R., Petersen, R.C., Xy, Y., O'Brien, P.C., Smith, G.E., Ivnik, R.J., Tangalos, E.G., & Kokmen, E. (1998). Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology, 51, 993–999.
Jernigan, T.L., Press, G.A., & Hesselink, J.R. (1990). Methods for measuring brain morphologic features on magnetic resonance images: Validation and normal aging. Archives of Neurology, 47, 27–32.
Jernigan, T.L., Archibald, S.L., Berhow, M.T., Sowell, E.R., Foster, D.S., & Hesselink, J.R. (1991a). Cerebral structure on MRI, Part I: Localization of age-related changes. Biological Psychiatry, 29, 55–67.
Jernigan, T.L., Salmon, D.P., Butters, N., & Hesselink, J.R. (1991b). Cerebral structure on MRI, Part II: Specific changes in Alzheimer's and Huntington's diseases. Biological Psychiatry, 29, 68–81.10.1016/0006-3223(91)90211-4
Jernigan, T.L. & Ostergaard, A.L. (1993). Word priming and recognition memory are both affected by mesial temporal lobe damage. Neuropsychology, 7, 14–26.10.1037/0894-4105.7.1.14
Jernigan, T.L., Ostergaard, A.L., & Fennema-Notestine, C. (2001a). Mesial temporal, diencephalic, and striatal contributions to deficits in single word reading, word priming, and recognition memory. Journal of the International Neuropsychological Society, 7, 63–78.10.1017/S1355617701711071
Jernigan, T.L., Archibald, S.L., Fennema-Notestine, C., Gamst, A., Stout, J.C., Bonner, J., & Hesselink, J. (2001b). Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiology of Aging, 22, 581–594.
Jones-Gotman, M. & Zatorre, R.J. (1993). Odor recognition memory in humans: role of right temporal and orbitofrontal regions. Brain and Cognition, 22, 182–198.10.1006/brcg.1993.1033
Kaplan, E., Goodglass, H., & Weintraub, S. (1983). The Boston Naming Test. Philadelphia: Lea & Febiger.
Kesslak, J.P., Nalcioglu, O., & Cotman, C. (1991). Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease. Neurology, 41, 51–54.
Kettenmann, B., Hummel, C., Stefan, H., & Kobal, G. (1997). Multiple olfactory activity in the human neocortex identified by magnetic source imaging. Chemical Senses, 22, 493–502.
Knupfer, L. & Spiegel, R. (1986). Differences in olfactory test performance between normal aged, Alzheimer and vascular type dementia individuals. International Journal of Geriatric Psychiatry, 1, 3–14.10.1002/gps.930010103
Koss, E. (1986). Olfactory dysfunction in Alzheimer's disease. Developmental Neuropsychology, 2, 89–99.10.1080/87565648609540332
Levy, L.M., Henkin, R.I., Hutter, A., Lin, C.S., Martins, D., & Schellinger, D. (1997). Functional MRI of human olfaction. Journal of Computer Assisted Tomography, 21, 849–856.10.1097/00004728-199711000-00002
Lorig, T.S., Elmes, D.G., Zald, D.H., & Pardo, J.V. (1999). A computer-controlled olfactometer for fMRI and electrophysiological studies of olfaction. Behavior Research Methods, Instruments, and Computers, 31, 370–375.
Martin, A. (1999). Automatic activation of the medial temporal lobe during encoding: Lateralized influences of meaning and novelty. Hippocampus, 9, 62–70.10.1002/(SICI)1098-1063(1999)9:1<62::AID-HIPO7>3.0.CO;2-K
Mattis, S. (1976). Mental status examination for organic mental syndrome in the elderly patient. In L. Bellak & T.B. Katasu (Eds.), Geriatric psychiatry: A handbook for psychiatrists and primary care physicians (pp. 77–121). New York: Grune & Statton.
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E.M. (1984). Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.10.1212/WNL.34.7.939
Morgan, C.D., Covington, J.W., Geisler, M.W., Polich, J., & Murphy, C. (1997). Olfactory event-related potentials: Older males demonstrate the greatest deficits. Electroencephalography and Clinical Neurophysiology, 104, 351–358.10.1016/S0168-5597(97)00020-8
Morgan, C., Geisler, M.W., Covington, J.W., Polich, J., & Murphy, C. (1999). Olfactory P3 in young and older adults. Psychophysiology, 36, 281–287.10.1017/S0048577299980265
Morgan, C.D. & Murphy, C. (2002). Olfactory event-related potentials in Alzheimer's disease. Journal of the International Neuropsychological Society, 753–763.
Morgan, C.D., Nordin, S., & Murphy, C. (1995). Odor identification as an early marker for Alzheimer's disease: Impact of lexical functioning and detection sensitivity. Journal of Clinical and Experimental Neuropsychology, 17, 793–803.10.1080/01688639508405168
Murphy, C. (1983). Age-related changes in the threshold, psychophysical function and pleasantness of menthol. Journal of Gerontology, 38, 217–222.
Murphy, C. (1993). Senescence and clinical changes in the olfactory system: Psychophysical considerations. In Development, growth and senescence in the chemical senses (pp. 153–160). Bethesda, MD: NIH Publication No. 93-3483.
Murphy, C. (1999). Loss of olfactory function in dementing disease. Physiology and Behavior, 66, 177–182.
Murphy, C., Anderson, J., & Markinson, S. (1994a). Psychophysical assessment of chemosensory disorders in clinical populations. In K. Kurihara, N. Suzuki, & H. Ogawa (Eds.), Olfaction and taste, XI, (pp. 609–613). New York: Springer-Verlag.10.1007/978-4-431-68355-1_251
Murphy, C., Bacon, A.W., Bondi, M.W., & Salmon, D.P. (1998). Apolipoprotein E status is associated with odor identification deficits in non-demented older persons. Annals of the New York Academy of Sciences, 855, 744–750.
Murphy, C., Cain, W.S., Gilmore, M.M., & Skinner, B. (1991). Sensory and semantic factors in recognition memory for odors and graphic stimuli: Elderly versus young persons. American Journal of Psychology, 104, 161–192.
Murphy, C., Gilmore, M.M., Seery, C.S., Salmon, D.P., & Lasker, B.P. (1990). Olfactory thresholds are associated with degree of dementia in Alzheimer's disease. Neurobiology of Aging, 11, 465–469.
Murphy, C., Lasker, B.R., & Salmon, D.P. (1987). Olfactory dysfunction and odor memory in Alzheimer's disease, Huntington's disease and normal aging. Society for Neuroscience Abstracts, 13, 1403.
Murphy, C. & Morgan, C.D. (2001). Olfactory function and event-related potentials in Alzheimer's disease. In K. Iqbal, S.S. Sisodia, & B. Winglad (Eds.), Alzheimer's disease: Advances in etiology, pathogensis and therapeutics (pp. 237–251). London: Wiley.
Murphy, C., Morgan, C.D., Geisler, M.W., Wetter, S., Covington, J.W., Madowitz, M.D., Nordin, S., & Polich, J. (2000). Olfactory event-related potentials and aging: Normative data. International Journal of Psychophysiology, 36, 133–145.
Murphy, C., Nordin, S., & Acosta, L. (1997). Odor learning, recall and recognition memory in young and elderly adults. Neuropsychology, 11, 126–137.
Murphy, C., Nordin, S., de Wijk, R.A., Cain, W.S., & Polich, J. (1994b). Olfactory-evoked potentials: Assessment of young and elderly, and comparison to psychophysical threshold. Chemical Senses, 19, 47–56.
Niccoli-Waller, C.A., Harvey, J., Nordin, S., & Murphy, C. (1999). Deficit in remote odor memory as measured by familiarity in Alzheimer's disease. Journal of Adult Development, 6, 131–136.
Nordin, S., Monsch, A., & Murphy, C. (1995). Unawareness of smell loss in normal aging and Alzheimer's disease: Discrepancy between self-reported and diagnosed smell sensitivity, Journal of Gerontology, 50B, P187–P192.
Nordin, S. & Murphy, C. (1996). Impaired sensory and cognitive olfactory function in questionable Alzheimer's disease. Neuropsychology, 10, 112–119.
Nyberg, L., McIntosh, A.R., Houle, S., Nilsson, L.G., & Tulving, E. (1996). Activation of medial temporal structures during episodic encoding. Nature, 380, 715–717.
O'Donnell, B.F., Friedman, S., Swearer, J.M., & Drachman, D. (1992). Active and passive P300 latency and psychometric performance: influence of age and individual differences. International Journal of Psychophysiology, 12, 187–195.
Ohm, T.G. & Braak, H. (1987). Olfactory bulb changes in Alzheimer's disease. Acta Neuropathologica (Berlin), 73, 365–369.10.1007/BF00688261
Petersen, R.C., Jack, C.R., Xu, Y.-C., Waring, S.C., O'Brien, P.C., Smith, G.E., Ivnik, R.J., Tangalos, E.G., Boeve, B.F., & Kokmen, E. (2000). Memory and MRI-based hippocampal volumes in aging and AD. Neurology, 54, 581–587.10.1212/WNL.54.3.581
Price, J.L. (1985). Beyond the primary olfactory cortex: Olfactory-related areas in the neocortex, thalamus and hypothalamus. Chemical Senses, 10, 239–258.
Price, J.L. (1987). The central olfactory and accessory olfactory systems. In T.E. Finger & W.L. Silver (Eds.), Neurobiology of taste and smell (pp. 179–203). New York: Wiley.
Price, J.L., Davis, P.B., Morris, J.C., & White, D.L. (1991). The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiology of Aging, 12, 295–312.
Raz, N., Raz, S., Yeo, R.A., Turkheimer, E., Bigler, E.D., & Cullum, C.M. (1987). Relationship between cognitive and morphological asymmetry in dementia of the Alzheimer type: A CT scan study. International Journal of Neuroscience, 35, 225–232.
Rombouts, S.A.R.B., Barkhof, F., Witter, M.P., & Scheltens, P. (2000). Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease. Neuroscience Letters, 285, 231–233.10.1016/S0304-3940(00)01067-3
Royet, J.P., Koenig, O., Gregoire, M.C., Cinotti, L., Lavenne, F., Le Bars, D., Costes, N., Vigouroux, M., Farget, V., Sicard, G., Holley, A., Mauguiere, F., Comar, D., & Froment, J.C. (1999). Functional anatomy of perceptual and semantic processing for odors. Journal of Cognitive Neuroscience, 11, 94–109.
Savic, I. & Berglund, H. (2000). Right-nostril dominance in discrimination of unfamiliar, but not familiar odours. Chemical Senses, 25, 517–523.
Savic, I., Gulyas, B., Larsson, M., & Roland, P. (2000). Olfactory functions are mediated by parallel and hierarchical processing. Neuron, 26, 735–745.
Schiffman, S.S. (1997). Taste and smell losses in normal aging and disease. Journal of the American Medical Association, 278, 1357–1362.10.1001/jama.1997.03550160077042
Serby, M., Corwin, J., Novatt, A., Conrad, P., & Rotrosen, J. (1985). Olfaction in dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 48, 848–849.
Small, D.M., Jones-Gotman, M., Zatorre, R.J., Petrides, M., & Evans, A.C. (1997). Flavor processing: More than the sum of its parts. Neuroreport, 8, 3913–3917.
Sobel, N., Prabhakaran, V., Zhao, Z., Desmond, J.E., Glover, G.H., Sullivan, E.V., & Gabrieli, J.D. (2000). Time course of odorant-induced activation in the human primary olfactory cortex. Journal of Neurophysiology, 83, 537–551.
Sowell, E.R., Thompson, P.M., Holmes, C.J., Batth, R., Jernigan, T.L., & Toga, A. (1999a). Localizing age-related changes in brain structure between childhood and adolescence using Statistical Parametric Mapping. NeuroImage, 9, 587–597.
Sowell, E.R., Thompson, P.M., Holmes, C.J., Jernigan, T.L., & Toga, A.W. (1999b). In vivo evidence for post-adolescent brain maturation in frontal and striatal regions [Letter to the editor]. Nature Neuroscience, 2, 859–861.
Squire, L.R. (1992). Declarative and nondeclarative memory: Multiple brain systems supporting learning and memory. Journal of Cognitive Neuroscience, 4, 232–242.
Stout, J.C., Jernigan T.L., & Archibald S.L., Salmon D.P. (1996). Association of dementia severity with cortical grey matter and abnormal white matter volumes in dementia of the Alzheimer type. Archives of Neurology, 53, 742–749.
Stout, J.C., Bondi, M.W., Jernigan, T.L., Archibald, S.L., Delis, D.C., & Salmon, D.P. (1999). Regional cerebral volume loss associated with verbal learning and memory in dementia of the Alzheimer Type. Neuropsychology, 13, 188–197.
Thesen, T. & Murphy, C. (2001). Age-related changes in olfactory processing detected with olfactory event-related brain potentials using velopharyngeal closure and natural breathing. International Journal of Psychophysiology, 40, 19–27.
Toledo-Morrell, L., Dickerson, G., Sullivan, M.P., Spanovic, C., Wilson, R., & Bennett, D.A. (2000). Hemispheric differences in hippocampal volume predict verbal and spatial memory performance in patients with Alzheimer's disease. Hippocampus, 10, 136–142.10.1002/(SICI)1098-1063(2000)10:2<136::AID-HIPO2>3.0.CO;2-J
Tulving, E., Habib, R., Nyberg, L., Lepage, M., & McIntosh, A.R. (1999). Positron emission tomography correlations in and beyond medial temporal lobes. Hippocampus, 9, 71–82.10.1002/(SICI)1098-1063(1999)9:1<71::AID-HIPO8>3.0.CO;2-F
Waldton, S. (1974). Clinical observations of impaired cranial nerve function in senile dementia. Acta Psychiatrica Scandinavica, 50, 539–547.
Wenham, P.R., Price, W.H., & Blundell, G. (1991). Apolipoprotein E typing by one-stage PCR. Lancet, 337, 1158–1159.
Youngentob, S.L., Kurtz, D.B., Leopold, D.A., Mozell, M.M., & Hornung, D.E. (1982). Olfactory sensitivity: Is there laterality? Chemical Senses, 7, 11–21.
Yousem, D.M., Williams, S.C., Howard, R.O., Andrew, C., Simmons, A., Allin, M., Geckle, R.J., Suskind, D., Bullmore, E.T., Brammer, M.J., & Doty, R.L. (1997). Functional MR imaging during odor stimulation: Preliminary data. Radiology, 204, 833–838.
Zald, D.H. & Pardo, J.V. (1997). Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. Proceedings of the National Academy of Sciences USA, 94, 4119–4124.10.1073/pnas.94.8.4119
Zald, D.H. & Pardo, J.V. (2000). Functional neuroimaging of the olfactory system in humans. International Journal of Psychophysiology, 36, 165–181.
Zatorre, R.J. & Jones-Gotman, M. (2000). Functional imaging of the chemical senses. In A.W. Toga & J.C. Mazziotta (Eds.), Brain mapping: The applications (pp. 403–424). San Diego, CA: Academic.
Zatorre, R.J., Jones-Gotman, M., Evans, A.C., & Meyer, E. (1992). Functional localization and lateralization of human olfactory cortex. Nature, 360, 339–340.

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Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: A structural MRI study

  • Murphy Claire (a1) (a2), Jernigan Terry L. (a3) (a2) and Fennema-Notestine Christine (a3) (a2)

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