Smell Loss Before Alzheimer’s Used to Direct Therapy

A new study suggests an individual’s impaired sense of smell can be used to determine if they will respond to a specific type of medication to treat Alzheimer’s disease before it ever develops.

Researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI) explain that having an impaired sense of smell is recognized as one of the early signs of cognitive decline before the clinical onset of Alzheimer’s disease.

In the study, investigators discovered a way to use the loss of smell to determine if patients with mild cognitive impairment may respond to cholinesterase inhibitor drugs to treat Alzheimer’s disease.

Impaired cholinergic function contributes to Alzheimer’s disease (AD), affecting cognition, behavior and activities of daily living. The reduced production of the neurotransmitter acetylcholine impairs both memory and learning, two important components of AD.

Investigators discovered mediations, such as donepezil, can enhance cholinergic function by increasing the transmission of the neurotransmitter acetylcholine in the brain.

However, they have not been proven effective as a treatment for individuals with mild cognitive impairment (MCI), a condition that markedly increases the risk of Alzheimer’s disease.

The findings appear online in the Journal of Alzheimer’s Disease.

“We know that cholinesterase inhibitors can make a difference for Alzheimer’s patients, so we wanted to find out if we could identify patients at risk for Alzheimer’s who might also benefit from this treatment,” said D.P. Devanand, M.B.B.S., M.D.

“Since odor identification tests have been shown to predict progression to Alzheimer’s, we hypothesized that these tests would also allow us to discover which patients with MCI would be more likely to improve with donepezil treatment.”

In this year-long study, 37 participants with MCI underwent odor identification testing with the University of Pennsylvania Smell Identification Test (UPSIT). The test was administered before and after using an atropine nasal spray that blocks cholinergic transmission.

The patients were then treated with donepezil for 52 weeks, and were periodically reevaluated with the UPSIT and with memory and cognitive function tests.

Those who had a greater decline in UPSIT scores, indicating greater cholinergic deficits in the brain, after using the anticholinergic nasal spray test saw greater cognitive improvement with donepezil.

In addition, short-term improvement in odor identification from baseline to eight weeks tended to predict longer-term cognitive improvement with donepezil treatment over one year.

“These results, particularly if replicated in larger populations, suggest that these simple inexpensive strategies have the potential to improve the selection of patients with mild cognitive impairment who are likely to benefit from treatment with cholinesterase inhibitors like donepezil,” said Devanand.

Source: Columbia University