Odor Identification Impairment and Change with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment

Abstract

Background: Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease (AD) pathology, and short-term change in odor identification impairment with cholinesterase inhibitor (CheI) treatment may predict longer term cognitive outcomes. Objective: In patients with mild cognitive impairment (MCI) treated prospectively with donepezil, a CheI, for 52 weeks, to determine if 1) acute decline in odor identification ability with anticholinergic challenge can predict cognitive improvement, and 2) change in odor identification over 8 weeks can predict cognitive improvement. Methods: MCI was diagnosed clinically without AD biomarkers. At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and this dose was maintained for 52 weeks. Main outcomes were ADAS-Cog total score and Selective Reminding Test (SRT) total immediate recall score measured at baseline, 26 and 52 weeks. Results: In 100 study participants, mean age 70.14 (SD 9.35) years, atropine-induced decrease in UPSIT score at baseline was not associated with change in ADAS-Cog or SRT scores over 52 weeks. Change in UPSIT score from 0 to 8 weeks did not show a significant association with change in the ADAS-Cog or SRT measures over 52 weeks.

Odor identification impairment and cholinesterase inhibitor treatment in Alzheimer's disease

“…The current study aimed to evaluate acute change in odor identification following atropine nasal spray challenge as a predictor of long‐term improvement in patients with mild to moderate AD who receive ACheI (donepezil) treatment. Results for patients with mild cognitive impairment (MCI) from an independent sample enrolled in a separate study conducted in parallel have been reported previously 7 . In the current study of patients with mild to moderate AD treated with donepezil, we hypothesized that: (1) the atropine effect (an acute decrease in odor identification test scores from pre‐ to post‐atropine challenge at baseline) would predict improved cognitive and global functioning from baseline to weeks 26 and 52; and (2) increase in odor identification test scores after 8 weeks would predict improved cognitive and global functioning from baseline to weeks 26 and 52.…”

“…Our group previously reported atropine‐induced decrease in UPSIT was associated with increased verbal memory (SRT total recall) and global improvement (CIBIC‐plus), but not global cognition (ADAS‐Cog) over 52 weeks in a sample of 37 patients with MCI treated with donepezil 29 . These earlier findings were not replicated in a more recent trial with a larger sample of 100 MCI patients, where atropine‐induced decrease in UPSIT was not associated with longitudinal change in any cognitive or functional outcome measures 7 . Collectively, results of these studies do not support the use of atropine challenge to reliably improve selection of patients to receive clinical treatment with cholinesterase inhibitors, regardless of phase of clinically defined AD.…”

“…Results for patients with mild cognitive impairment (MCI) from an independent sample enrolled in a separate study conducted in parallel have been reported previously. 7 In the current study of patients with mild to moderate AD treated with donepezil, we hypothesized that: (1)…”

“…Cholinergic neurons are prominent in the olfactory bulb and entorhinal cortex 3 ; therefore, deficits in odor identification in early AD may indicate the loss of cholinergic inputs to the olfactory brain regions and higher order projection areas for olfactory processing, including the anterior olfactory nucleus, orbitofrontal cortex, piriform cortex, amygdala, entorhinal cortex, and hippocampus 4,5 . These deficits manifest clinically as poor performance on tests of standardized odor identification 6,7 …”

Exploration on the Improvement of Cognitive Function and Inflammatory Response in Perimenopausal Patients with Mild Cognitive Impairment by Self-Prepared Ningshen Prescription

“…There is still a lack of authoritative statements on the pathogenesis of MCI, and the drugs that are more widely used clinically for treatment are those that mainly improve symptoms, such as cholinesterase inhibitor (acetylcholinesterase inhibitor, AchEI) and ionotropic glutamate receptor antagonist (N-methyl-D-aspartate receptor), but according to the available findings [ 6 , 7 ], there is still no significant evidence on the efficacy of these drugs in intervening the conversion rate of MCI to dementia, and further studies are needed to confirm this. In recent years, with in-depth research on MCI, Chinese medicine has achieved good results in improving symptoms, delaying the disease, and improving patients' quality of life, and the investigation of its intrinsic mechanism has received a lot of attention from clinical workers [ 8 , 9 ].…”