Olfactory Dysfunction as a Global Biomarker for Sniffing out Alzheimer’s Disease: A Meta-Analysis

Abstract

Cases of Alzheimer’s disease (AD) are rising exponentially due to increasing global life expectancy. There are approximately 50 million sufferers worldwide, with prevalence rising most rapidly in low-income countries such as Africa and Asia. There is currently no definite diagnosis of AD until after death, thus an early biomarker for AD is urgently required in order to administer timelier and more effective interventions. Olfactory dysfunction (problems with the sense of smell) is one of the earliest, preclinical symptoms observed in AD. Olfaction is a promising early biomarker for use worldwide as it is easy, cheap to measure, and not reliant on specialist clinicians or laboratory analysis. We carried out a meta-analysis to determine the credibility of olfaction in diagnosing AD in the preclinical stages, by comparing olfaction in healthy controls against AD patients and patients with mild cognitive impairment (MCI). Data from 10 articles were subjected to two comparative meta-analyses. In the case of AD, the results illustrated that the overall magnitude of effect size was more apparent, d = −1.63, 95% CI [−1.95, −1.31], in comparison to that of MCI, d = −0.81, 95% CI [−1.08, −0.55]. This shows that olfaction worsens progressively as patients progress from MCI to AD, highlighting the potential for olfactory dysfunction to identify AD in the preclinical stages prior to MCI.

Cerebrospinal fluid and optic nerve sheath compartment syndrome: A common pathophysiological mechanism in five different cases?

“…AD is characterized by excessive accumulation of toxic forms of amyloid-beta (Aβ). 22 Aβ deposition has been found earlier within the olfactory bulb than in any other brain region in rodent models of AD, suggesting the presence of olfactory dysfunction. 26 The pathology of AD includes atrophy of the subcortical grey matter of the brain, 27 a phenomenon that also occurs in both NTG and primary open-angle glaucoma patients in both the visual pathways and in non-visual brain regions.…”

“…We believe that the pathology of impaired CSF flow is one of the pathophysiological mechanisms of brain injury in neurodegenerative diseases. It has been described in olfactory dysfunction as well as in patients with idiopathic intracranial hypertension (IIH), AD and glaucoma …”

“…Several studies have also shown olfactory impairment associated with spatial memory loss in AD. AD is characterized by excessive accumulation of toxic forms of amyloid‐beta (Aβ) . Aβ deposition has been found earlier within the olfactory bulb than in any other brain region in rodent models of AD, suggesting the presence of olfactory dysfunction …”

Detection and recognition thresholds for five basic tastes in patients with mild cognitive impairment and Alzheimer’s disease dementia

“…Olfactory function declines in patients with Alzheimer's disease dementia (ADD) [1][2][3][4], and hearing loss is a risk factor for dementia onset [5][6][7], indicating that there are associations between sensory disorders and dementia. In terms of the sense of taste, gustatory function has been shown to be decreased in patients with ADD [8][9][10], and 81.4% of patients with ADD show some eating disturbance, such as changes in appetite and eating habits [11].…”

Cut-Off Scores of an Olfactory Function Test for Mild Cognitive Impairment and Dementia

“…Olfactory function is divided into three odor categories: 1) odor detection threshold: the molecular concentration that can be detected by an individual; 2) discrimination: ability to distinguish one odor from other odors; and 3) identification: to associate odor molecules with related words or images [ 15 - 17 ]. All of these three olfactory functional domains are impaired in MCI and AD patients compared to healthy controls [ 16 , 18 ]. Moreover, olfactory dysfunction is known to appear prior to cognitive decline in AD [ 18 ].…”