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January 13, 2015; 84 (2) Article

Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

D.P. Devanand, Seonjoo Lee, Jennifer Manly, Howard Andrews, Nicole Schupf, Richard L. Doty, Yaakov Stern, Laura B. Zahodne, Elan D. Louis, Richard Mayeux
First published December 3, 2014, DOI: https://doi.org/10.1212/WNL.0000000000001132
D.P. Devanand
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Seonjoo Lee
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Jennifer Manly
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Howard Andrews
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Nicole Schupf
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Richard L. Doty
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Yaakov Stern
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Laura B. Zahodne
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Elan D. Louis
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Richard Mayeux
From the Division of Geriatric Psychiatry, Department of Psychiatry (D.P.D.), Department of Neurology and the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (J.M., H.A., N.S., Y.S., L.B.Z., E.D.L., R.M.), College of Physicians and Surgeons, Columbia University, New York; Division of Biostatistics (S.L.), New York State Psychiatric Institute and Columbia University, New York; and University of Pennsylvania (R.L.D.), Philadelphia.
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Citation
Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community
D.P. Devanand, Seonjoo Lee, Jennifer Manly, Howard Andrews, Nicole Schupf, Richard L. Doty, Yaakov Stern, Laura B. Zahodne, Elan D. Louis, Richard Mayeux
Neurology Jan 2015, 84 (2) 182-189; DOI: 10.1212/WNL.0000000000001132

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Abstract

Objective: To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia.

Methods: In a multiethnic community cohort in North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years.

Results: In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval [CI] 1.040, 1.095; p < 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p < 0.0001) after including covariates. UPSIT, but not Selective Reminding Test–total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p < 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p < 0.0001) after including demographic, cognitive, and functional covariates.

Conclusions: Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the cross-cultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.

GLOSSARY

AD=
Alzheimer disease;
AUC=
area under the curve;
CI=
confidence interval;
HR=
hazard ratio;
MCI=
mild cognitive impairment;
ROC=
receiver operating characteristic;
RR=
relative risk;
SRT=
Selective Reminding Test;
SRT-TR=
Selective Reminding Test–total immediate recall;
UPSIT=
University of Pennsylvania Smell Identification Test;
WHICAP=
Washington Heights/Inwood Columbia Aging Project

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received July 7, 2014.
  • Accepted in final form September 24, 2014.
  • © 2014 American Academy of Neurology
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