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

Motter, Jeffrey N.; Liu, Xinhua; Qian, Min; Cohen, Hannah; Devanand, Davangere P.

doi:10.1002/dad2.12158

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…In preclinical AD, patients can experience subjective cognitive decline that causes them concern, although classic neuropsychological tests are not able to detect any change in cognition at this time …”

Section: Pathophysiologymentioning

confidence: 99%

International consensus statement on allergy and rhinology: Olfaction

Patel

Holbrook

Turner

et al. 2022

Int Forum Allergy Rhinol

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Background:The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results:The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion:This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

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Section: Pathophysiologymentioning

confidence: 99%

International consensus statement on allergy and rhinology: Olfaction

Patel

Holbrook

Turner

et al. 2022

Int Forum Allergy Rhinol

View full text Add to dashboard Cite

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“…However, results regarding the impact of AChEIs on olfactory function in patients with AD are inconsistent. Some studies have found that olfactory function is improved by treatment with AChEIs (34,35) and have even suggested that atropine challenge is indicative of a cognitive response to AChEI treatment; however, further studies did not confirm these findings (36,37). It is important to note that odor identification was tested in these studies, and olfactory memory was not specifically analyzed.…”

Section: Discussionmentioning

confidence: 87%

Olfactory memory in mild cognitive impairment and Alzheimer’s disease

et al. 2023

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IntroductionOlfaction is impaired in Alzheimer’s disease (AD). However, olfactory memory has rarely been examined. As the pathogenesis of AD remains largely unknown, collecting more data regarding the occurrence and progression of its symptoms would help gain more insight into the disease.ObjectiveTo investigate olfactory memory and its relationship with verbal memory and other clinical features in patients with early-stage AD.MethodsThree groups of participants were enrolled in this study: patients with mild dementia due to AD (MD-AD, N = 30), patients with mild cognitive impairment due to AD (MCI-AD, N = 30), and cognitively normal older participants (CN, N = 30). All participants underwent cognitive evaluation (Clinical Dementia Rating scale, Mini Mental State Examination, Alzheimer’s Disease Assessment Scale–Cognitive Subscale, delayed verbal recall, and verbal fluency tests) and assessment of olfactory immediate and delayed recognition memory.ResultsOlfactory immediate and delayed recognition memory scores were significantly lower in the MD-AD group than in the MCI-AD and CN groups. The MCI-AD and CN groups did not differ significantly [in both cases, Kruskal–Wallis test, p < 0.05; post hoc analysis revealed significant differences between the MD-AD and MCI-AD groups and between the MD-AD and CN groups (p < 0.05), and no significant difference between the MCI-AD and CN groups (p > 0.05)]. Verbal immediate recall, delayed recall after 5 min, and delayed recall after 30 min scores were significantly worse in the MD-AD and MCI-AD groups than in the CN group. MD-AD and MCI-AD groups did not differ significantly [in all cases Kruskal–Wallis test, p < 0.05; post hoc analysis revealed significant differences between MD-AD and CN groups, and MCI-AD and CN groups (p < 0.05) and no significant difference between MD-AD and MCI-AD groups (p > 0.05)]. Duration of AD symptoms was a strong predictor of both immediate and delayed olfactory recognition memory scores.ConclusionOlfactory memory impairment was observed in patients with AD. The changes progress during the course of the disease. However, unlike verbal memory, olfactory memory is not significantly impaired in the prodromal stage of AD.

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“…However, change in UPSIT after atropine challenge was not associated with AChEI benefit, contrarily to the previously cited study. The authors hypothesized that this lack of association was due to the fact that atropine, administered through nasal spray, might have not reached the olfactory bulb, but the small sample may have also contributed to this negative finding (Motter et al, 2021 ). Although it did not include patients with neurodegenerative dementias, a small RCT by Pelton suggested that a lower UPSIT score could predict cognitive response to donepezil at 3 months in depressed patients with cognitive impairment, reinforcing the hypothesis that AChEI therapy would be generally beneficial in patients with hallmarks of cholinergic deficit, irrespective of the diagnosis (Pelton et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

et al. 2022

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BackgroundThe mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results.MethodsWe conducted a systematic review of the literature up to December 31st, 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: predict*AND respon*AND (acetylcholinesterase inhibitors OR donepezil OR rivastigmine OR galantamine). The results were presented narratively.ResultsWe identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included.DiscussionThe studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.

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

Cited by 3 publications

References 36 publications

International consensus statement on allergy and rhinology: Olfaction

International consensus statement on allergy and rhinology: Olfaction

Olfactory memory in mild cognitive impairment and Alzheimer’s disease

Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review

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