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Letter to the Editor   |    
Olfactory Deficit in Alzheimer's Disease?
RICHARD L. DOTY, PH.D.
Am J Psychiatry 2001;158:1533-a-1534. doi:10.1176/appi.ajp.158.9.1533-a

To the Editor: I read with great interest the article by Dr. Devanand et al. Although this is a fascinating and important study that is in general accordance with another recent prospective study (1), there are several errors that should be pointed out.

First, the authors stated that deficits in olfactory identification are not consistently seen in patients with Huntington’s disease. In fact, olfactory loss is common in patients with Huntington’s disease once the clinical signs of the disorder are manifest. For example, in one study (2), 25 of 25 Huntington’s disease patients exhibited Pennsylvania Smell Identification Test scores below those of matched comparison subjects and at-risk asymptomatic relatives. This is nearly equivalent to the finding reported by my colleagues and me in 1987 (3) that 23 of 25 patients with early-stage Alzheimer’s disease who were capable of psychophysical testing scored below matched normal comparison subjects on the Pennsylvania Smell Identification Test. In accordance with the general thesis of Dr. Devanand et al., we found in this early study that only two of 34 patients with Alzheimer’s disease were aware of their deficit.

Second, the authors stated that the findings relative to olfactory losses for Parkinson’s disease are "equivocal." In fact, the prevalence and magnitude of olfactory losses of patients with Parkinson’s disease are indistinguishable from those seen in early-stage Alzheimer’s disease, both in terms of scores on the Pennsylvania Smell Identification Test and threshold values (4, 5).

Dr. Devanand et al., as well as others, have asked whether many older patients with olfactory losses and marginal cognitive impairment already have Alzheimer’s disease that has not progressed clinically to the point at which it can meet the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association. If so, then a redefinition of the operational criteria for establishing the presence of Alzheimer’s disease at its earliest stages may be in the offing, perhaps incorporating criteria determined from both olfactory tests and magnetic resonance imaging (MRI) (6).

Graves AB, Bowen JD, Rajaram L, McCormick WC, McCurry SM, Schellenberg GD, Larson EB: Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E e4 status. Neurology 1999; 53:1480-  1487
 
Moberg PJ, Doty RL: Olfactory function in Huntington’s disease patients and at-risk offspring. Int J Neurosci  1997; 89:133-139
[PubMed]
[CrossRef]
 
Doty RL, Reyes PF, Gregor T: Presence of both odor identification and detection deficits in Alzheimer’s disease. Brain Res Bull  1987; 18:597-600
[PubMed]
[CrossRef]
 
Doty RL, Deems DA, Stellar S: Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 1988; 38:1237-  1244
 
Doty RL, Perl DP, Steele JC, Chen KM, Pierce JD Jr, Reyes P, Kurland LT: The odor identification deficit of the parkinsonism-dementia complex of Guam: equivalence to that of Alzheimer’s and idiopathic Parkinson’s disease. Neurology 1991; 41(suppl 2):77-80
 
Killiany RJ, Gomez-Isla T, Moss M, Kikinis R, Sandor T, Jolesz F, Tanzi R, Jones K, Hyman BT, Albert MS: Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Ann Neurol  2000; 47:430-439
[PubMed]
[CrossRef]
 
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References

Graves AB, Bowen JD, Rajaram L, McCormick WC, McCurry SM, Schellenberg GD, Larson EB: Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E e4 status. Neurology 1999; 53:1480-  1487
 
Moberg PJ, Doty RL: Olfactory function in Huntington’s disease patients and at-risk offspring. Int J Neurosci  1997; 89:133-139
[PubMed]
[CrossRef]
 
Doty RL, Reyes PF, Gregor T: Presence of both odor identification and detection deficits in Alzheimer’s disease. Brain Res Bull  1987; 18:597-600
[PubMed]
[CrossRef]
 
Doty RL, Deems DA, Stellar S: Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 1988; 38:1237-  1244
 
Doty RL, Perl DP, Steele JC, Chen KM, Pierce JD Jr, Reyes P, Kurland LT: The odor identification deficit of the parkinsonism-dementia complex of Guam: equivalence to that of Alzheimer’s and idiopathic Parkinson’s disease. Neurology 1991; 41(suppl 2):77-80
 
Killiany RJ, Gomez-Isla T, Moss M, Kikinis R, Sandor T, Jolesz F, Tanzi R, Jones K, Hyman BT, Albert MS: Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Ann Neurol  2000; 47:430-439
[PubMed]
[CrossRef]
 
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