Smell Test May Predict Treatment Response to Cholinesterase Inhibitors in Alzheimer's

Megan Brooks

November 10, 2015

BARCELONA — Deficits in sense of smell may help predict response to cholinesterase inhibitors in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD), a study suggests.

"The research is new and shows that low odor identification test performance is associated with improvement with treatment with donepezil (Aricept) and other cholinesterase inhibitors," Devangere P. Devanand, MBBS, MD, professor of psychiatry and neurology at Columbia University Medical Center in New York City, told Medscape Medical News.

"Clinical implications are that an odor identification test can be used to guide the decision to treat the patient with a cholinesterase inhibitor," Dr Devanand said.

He presented the findings at the 8th Clinical Trials Conference on Alzheimer's Disease (CTAD).

Neurofibrillary tangles in olfactory neurons and the olfactory bulb develop in the earliest stages of AD. Odor identification deficits increase the risk for transition from MCI to a clinical diagnosis of AD, with predictive utility similar to episodic verbal memory deficits, Dr Devanand and colleagues explain in their conference poster.

Currently, no biomarker consistently predicts improvement with a cholinesterase inhibitor. In a 3-month open-label pilot trial of patients with mild to moderate AD taking donepezil, improvement in University of Pennsylvania Smell Identification Test (UPSIT) scores correlated significantly with global improvement and activities of daily living.

These findings "indirectly suggest" that odor identification deficits will predict cognitive improvement with cholinesterase inhibitor treatment, the authors note.

In the study presented at CTAD, 148 patients with MCI were followed in a longitudinal naturalistic study of early markers of AD. During follow-up, 48 patients received treatment with a cholinesterase inhibitor based on doctor's choice.

The UPSIT was administered at baseline and 2 and 4 years later. The primary cognitive outcome was the 6-month change in Selective Reminding Test (SRT) total immediate recall score during cholinesterase inhibitor treatment.

In multiple regression analyses on change in SRT total recall scores, the baseline UPSIT by diagnosis (progression or nonprogression to AD) interaction was significant (β = –1.19; P = .001), Dr Devanand and colleagues report.

A lower baseline UPSIT score was associated with greater improvement in SRT total recall with cholinesterase inhibitor treatment in patients who progressed to AD (β = –0.43; P = .14), but this association went in the opposite direction in nonprogressors (β = 0.76; P < .001). The interaction remained significant after adjustment for SRT total recall before treatment, as well as age, sex, education, and apolipoprotein E ε4 status.

In patients with high UPSIT scores, there was no significant change in SRT total recall.

This study shows that olfactory identification impairment — an established biomarker that predicts cognitive decline and the transition from MCI to AD — is associated with improvement with cholinesterase inhibitor treatment in patients with MCI who progress to AD, the researchers conclude.

"This relatively simple, cost-effective, noninvasive test has the potential to identify" patients with MCI who are likely to benefit from a cholinesterase inhibitor, they say.

Actionable Data

Commenting on the results for Medscape Medical News, Cyrus Raji, MD, PhD, from the University of California, Los Angeles, "This is exactly the kind of study we need with respect to olfactory identification and Alzheimer's."

"In a previous systematic review I coauthored 3 years ago, we found that anosmia or loss of smell is definitely associated with MCI and Alzheimer's. However, we stressed the need in that publication for longitudinal studies. [This new] study not only fulfills this need in the literature but it also connects the data to actionable treatment decisions. This work should also encourage greater use of the UPSIT in clinical practice as anosmia is seen with other brain disease such as Parkinson's," Dr Raji explained.

The study was supported by the National Institute on Aging. The authors have disclosed no relevant financial relationships. Dr Raji consults for Brainreader, which makes Neuroreader, a US Food and Drug Administration–approved software application that measures brain volumes on MRI scans.

8th Clinical Trials Conference on Alzheimer's Disease (CTAD). Poster P2-46. Presented November 6, 2015.

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