Olfactory identification and incidence of mild cognitive impairment in older age.

CONTEXT Mild cognitive impairment (MCI) is often a precursor to Alzheimer disease, but knowledge about factors that predict its development is limited. OBJECTIVE To test the hypothesis that impaired odor identification is related to increased risk of incident MCI. DESIGN Longitudinal cohort study. SETTING Academic research. PARTICIPANTS Subjects were 589 community-dwelling older persons without cognitive impairment at study baseline, at which time odor identification was assessed using the 12-item Brief Smell Identification Test (mean +/- SD score, 9.3 +/- 1.9). MAIN OUTCOME MEASURES Incidence of MCI and rate of decline in cognitive function. RESULTS During annual observation of up to 5 years, 177 subjects developed MCI. In a proportional hazards model adjusted for age, sex, and education, odor identification score predicted development of MCI (relative risk, 1.15; 95% confidence interval, 1.07-1.23), with risk increased by 50% in persons with below-average (score of 8 [25th percentile]) compared with above-average (score of 11 [75th percentile]) odor identification scores. Results were not substantially changed in subsequent analyses that controlled for level of cognitive function or disability, presence of stroke, or smoking status at baseline or that required MCI to persist for at least 1 year. Impaired odor identification was also associated with a lower level of global cognition at baseline and with more rapid decline in episodic memory, semantic memory, and perceptual speed. CONCLUSION Among older persons without manifest cognitive impairment, difficulty in identifying odors predicts subsequent development of MCI.

[1]  S. Katz,et al.  STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. , 1963, JAMA.

[2]  M. Lawton,et al.  Assessment of Older People: Self-Maintaining and Instrumental Activities of Daily Living , 1969 .

[3]  David R. Cox,et al.  Regression models and life tables (with discussion , 1972 .

[4]  J. Ware,et al.  Random-effects models for longitudinal data. , 1982, Biometrics.

[5]  R. Doty,et al.  Development of the university of pennsylvania smell identification test: A standardized microencapsulated test of olfactory function , 1984, Physiology & Behavior.

[6]  G. V. Van Hoesen,et al.  Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. , 1984, Science.

[7]  K Y Liang,et al.  Longitudinal data analysis for discrete and continuous outcomes. , 1986, Biometrics.

[8]  Richard L. Doty,et al.  Presence of both odor identification and detection deficits in alzheimer's disease , 1987, Brain Research Bulletin.

[9]  R. Doty,et al.  Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test , 1989, Perception & psychophysics.

[10]  O Nalcioglu,et al.  Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease , 1991, Neurology.

[11]  R. Doty,et al.  Tests of human olfactory function: Principal components analysis suggests that most measure a common source of variance , 1994, Perception & psychophysics.

[12]  R. Doty,et al.  Development of the 12‐Item Cross‐Cultural Smell Identification Test(CC‐SIT) , 1996, The Laryngoscope.

[13]  D P Salmon,et al.  Very Early Changes in Olfactory Functioning Due to Alzheimer's Disease and the Role of Apolipoprotein E in Olfaction a , 1998, Annals of the New York Academy of Sciences.

[14]  P. Moberg,et al.  Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases. , 1998, Archives of neurology.

[15]  G. Schellenberg,et al.  Impaired olfaction as a marker for cognitive decline: Interaction with apolipoprotein E 4 status , 1999 .

[16]  K. Marder,et al.  Olfactory deficits in patients with mild cognitive impairment predict Alzheimer's disease at follow-up. , 2000, The American journal of psychiatry.

[17]  A. Smith,et al.  Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology , 2001, Journal of neurology, neurosurgery, and psychiatry.

[18]  N. Pedersen,et al.  Olfactory functioning and cognitive abilities: a twin study. , 2001, The journals of gerontology. Series B, Psychological sciences and social sciences.

[19]  Karen Ritchie,et al.  Classification criteria for mild cognitive impairment: A population-based validation study , 2001 .

[20]  D. Carmelli,et al.  Impaired Olfaction Predicts Cognitive Decline in Nondemented Older Adults , 2002, Neuroepidemiology.

[21]  M. Albert,et al.  MRI measures of entorhinal cortex vs hippocampus in preclinical AD , 2002, Neurology.

[22]  D. Royall,et al.  Severe Dysosmia Is Specifically Associated with Alzheimer-Like Memory Deficits in Nondemented Elderly Retirees , 2002, Neuroepidemiology.

[23]  Christelle Rochefort,et al.  Enriched Odor Exposure Increases the Number of Newborn Neurons in the Adult Olfactory Bulb and Improves Odor Memory , 2002, The Journal of Neuroscience.

[24]  D. A. Bennett,et al.  Natural history of mild cognitive impairment in older persons , 2002, Neurology.

[25]  Udo Rüb,et al.  Where Does Parkinson Disease Pathology Begin in the Brain? , 2002, Journal of neuropathology and experimental neurology.

[26]  R. Klein,et al.  Prevalence of olfactory impairment in older adults. , 2002, JAMA.

[27]  D. Berlau,et al.  Comparative study of aging in the mouse olfactory bulb , 2002, The Journal of comparative neurology.

[28]  J. Schneider,et al.  Individual differences in rates of change in cognitive abilities of older persons. , 2002, Psychology and aging.

[29]  Kenneth Rockwood,et al.  Variations in case definition affect prevalence but not outcomes of mild cognitive impairment , 2003, Neurology.

[30]  V. Fung,et al.  Identifying the pattern of olfactory deficits in Parkinson disease using the brief smell identification test. , 2003, Archives of neurology.

[31]  John Breitner,et al.  Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2. , 2003, Archives of neurology.

[32]  D. Bennett,et al.  Incidence of Alzheimer disease in a biracial urban community: relation to apolipoprotein E allele status. , 2003, Archives of neurology.

[33]  M. Mesulam,et al.  Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. , 2003, Archives of neurology.

[34]  Lisa Barnes,et al.  Assessment of Lifetime Participation in Cognitively Stimulating Activities , 2003, Journal of clinical and experimental neuropsychology.

[35]  H. Tuokko,et al.  Five-year follow-up of cognitive impairment with no dementia. , 2003, Archives of neurology.

[36]  H. Berendse,et al.  Idiopathic hyposmia as a preclinical sign of Parkinson's disease , 2004, Annals of neurology.

[37]  E. Reiman,et al.  Vascular risk factors, incidence of MCI, and rates of progression to dementia , 2004, Neurology.

[38]  H. Soininen,et al.  Incidence and Risk Factors for Mild Cognitive Impairment: A Population-Based Three-Year Follow-Up Study of Cognitively Healthy Elderly Subjects , 2004, Dementia and Geriatric Cognitive Disorders.

[39]  Paul E. Gilbert,et al.  The Effect of the ApoE ϵ4 Allele on Recognition Memory for Olfactory and Visual Stimuli in Patients with Pathologically Confirmed Alzheimer’s Disease, Probable Alzheimer’s Disease, and Healthy Elderly Controls , 2004, Journal of clinical and experimental neuropsychology.

[40]  Charles Duyckaerts,et al.  Dopamine depletion impairs precursor cell proliferation in Parkinson disease , 2004, Nature Neuroscience.

[41]  D. Bennett,et al.  Religious Orders Study: Overview and Change in Cognitive and Motor Speed , 2004 .

[42]  André Parent,et al.  Evidence of newly generated neurons in the human olfactory bulb. , 2004, Brain research. Developmental brain research.

[43]  Christopher Gregg,et al.  Aging Results in Reduced Epidermal Growth Factor Receptor Signaling, Diminished Olfactory Neurogenesis, and Deficits in Fine Olfactory Discrimination , 2004, The Journal of Neuroscience.

[44]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[45]  C. Zelano,et al.  Humans as an Animal Model for Systems-Level Organization of Olfaction , 2005, Neuron.

[46]  J. Schneider,et al.  Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions , 2005, Neurology.

[47]  Parkinsonian signs in subjects with mild cognitive impairment. , 2005, Neurology.

[48]  Yaakov Stern,et al.  A 10‐item smell identification scale related to risk for Alzheimer's disease , 2005, Annals of neurology.

[49]  D. Bennett,et al.  Early and late life cognitive activity and cognitive systems in old age , 2005, Journal of the International Neuropsychological Society.

[50]  David A. Bennett,et al.  The Rush Memory and Aging Project: Study Design and Baseline Characteristics of the Study Cohort , 2005, Neuroepidemiology.

[51]  D. Bennett,et al.  Odor Identification and Decline in Different Cognitive Domains in Old Age , 2006, Neuroepidemiology.

[52]  J. Schneider,et al.  Neuropathology of older persons without cognitive impairment from two community-based studies , 2006, Neurology.

[53]  E. Hirsch,et al.  Dopaminergic Substantia Nigra Neurons Project Topographically Organized to the Subventricular Zone and Stimulate Precursor Cell Proliferation in Aged Primates , 2006, The Journal of Neuroscience.

[54]  Charles D. Smith,et al.  Neuropathologic substrate of mild cognitive impairment. , 2006, Archives of neurology.

[55]  Anosmia is very common in the Lewy body variant of Alzheimer's disease , 2006 .

[56]  E. Tangalos,et al.  Neuropathologic features of amnestic mild cognitive impairment. , 2006, Archives of neurology.

[57]  W R Markesbery,et al.  Risk factors for transitions from normal to mild cognitive impairment and dementia , 2006, Neurology.

[58]  V. Pankratz,et al.  Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. , 2006, Archives of neurology.

[59]  D. Bennett,et al.  Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. , 2006, Neurology.

[60]  H. Buschke,et al.  Leisure activities and the risk of amnestic mild cognitive impairment in the elderly , 2006, Neurology.

[61]  D. Bennett,et al.  Mild cognitive impairment , 2006, Neurology.

[62]  David A. Bennett,et al.  Decision Rules Guiding the Clinical Diagnosis of Alzheimer’s Disease in Two Community-Based Cohort Studies Compared to Standard Practice in a Clinic-Based Cohort Study , 2006, Neuroepidemiology.

[63]  D A Bennett,et al.  The relationship between cerebral Alzheimer’s disease pathology and odour identification in old age , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[64]  J. Schneider,et al.  Loneliness and risk of Alzheimer disease. , 2007, Archives of general psychiatry.

[65]  J. Blass.  Leisure activities and the risk of amnestic mild cognitive impairment in the elderly , 2008 .

[66]  A. Nappi,et al.  Alzheimer ' s Disease : Cell-Specific Pathology Isolates the Hippocampal Formation , 2022 .