Olfactory decline is an early symptom of Alzheimer’s disease (AD) and is a predictor of conversion from mild cognitive impairment (MCI) to AD. Olfactory decline could reflect AD-related atrophy of structures related to the sense of smell. The aim of this study was to verify whether the presence of a clinical diagnosis of AD or MCI is associated with a volumetric decrease in the olfactory bulbs (OB) and the primary olfactory cortex (POC). We conducted two systematic reviews, one for each region and a meta-analysis. We collected articles from PsychNet, PubMed, Ebsco, and ProQuest databases. Results showed large and heterogeneous effects indicating smaller OB volumes in patients with AD (k = 6, g = −1.21, 95% CI [−2.19, −0.44]) and in patients with MCI compared to controls. There is also a trend for smaller POC in patients with AD or MCI compared to controls. Neuroanatomical structures involved in olfactory processing are smaller in AD and these volumetric reductions could be measured as early as the MCI stage.

Background: Recently, subjective cognitive decline (SCD) has been considered to be one of the first signs of Alzheimer’s disease (AD). Since this potential early marker is sensitive but not specific to AD, combining it with other markers could ensure higher accuracy when predicting which persons with SCD will convert to AD. Since olfactory dysfunction is observable in both AD and mild cognitive impairment (MCI), it is a promising marker that could help improve the early diagnosis of AD. Objective: The aim of this meta-analysis was to verify whether the presence of SCD is associated with a decrease in olfactory identification ability. Methods: We collected articles from the following databases: PsychNet, PubMed, Ebsco, and ProQuest using the keywords: “SCD”, “subjective cognitive decline”, “subjective cognitive impairment”, “subjective memory impairment”, “subjective memory decline”, “cognitive complaints”, “memory complaints”, “cognitive concerns”, “memory concerns”, “olfac*” and “smell”. We included articles according to the following criteria: 1) participants aged 50 and over; 2) presence of an SCD group or a conceptual equivalent; 3) presence of a healthy control group with the same age range; and 4) assessment of olfactory identification ability. Results: Five studies met the inclusion criteria. Small and homogeneous effects were observed for olfactory identification alteration in individuals with SCD relative to controls ( g = –0.16, 95% CI [–0.46, 0.14]). Conclusion: Despite the low number of studies included, the findings suggest that odor identification is slightly altered in SCD compared to healthy older adults. This alteration in individuals with SCD could be an early marker of AD.

Olfactory and declarative memory performances are associated, as both functions are processed by overlapping medial-temporal and prefrontal structures and decline in older adults. While a decline in olfactory identification may be related to a decline in declarative memory, the relationship between olfactory detection threshold and declarative memory remains unclear. In this meta-analysis, we assessed (i) the relationship between olfactory identification/detection threshold and verbal declarative memory in cognitively normal older adults, and (ii) the effect of age on these relationships. We included articles from PsychNet, PubMed, and Academic Search Complete according to the following criteria: (i) inclusion of cognitively normal older adults; (ii) assessment of episodic or semantic memory; and (iii) assessment of olfactory identification or detection threshold. Seventeen studies and 22 effect sizes were eligible and included in this meta-analysis. Olfactory identification was associated with episodic (small effect size: r = 0.19; k = 22) and semantic memory (small effect size: r = 0.16; k = 23). Similarly, the olfactory detection threshold was associated with both episodic (small to medium effect size: r = 0.25; k = 5) and semantic memory (small effect size: r = 0.17; k = 7). Age was found to moderate the relationship between olfactory detection threshold and memory performance. Both olfactory identification and detection threshold performances are associated with declarative memory in older adults, and age only moderates the relationship between olfactory detection threshold and declarative memory performances.

One of the major challenges in the diagnosis of Alzheimer's disease (AD) is to increase the specificity of the early diagnosis. While episodic memory impairment is a sensitive AD marker, other measures are needed to improve diagnostic specificity. A promising biomarker might be a cerebral atrophy of the central olfactory processing areas in the early stages of the disease since an impairment of olfactory identification is present at the clinical stage of AD. Our goal was therefore, (1) to evaluate the grey matter volume (GMV) of central olfactory processing regions in prodromal AD and (2) to assess its association with episodic memory. We included 34 cognitively normal healthy controls (HC), 92 individuals with subjective cognitive decline (SCD), and 40 with mild cognitive impairment (MCI). We performed regions of interest analysis (ROI) using two different approaches, allowing to extract GMV from (1) atlas-based anatomical ROIs and from (2) functional and non-functional subregions of these ROIs (olfactory ROIs and non-olfactory ROIs). Participants with MCI exhibited smaller olfactory ROIs GMV, including significant reductions in the piriform cortex, amygdala, entorhinal cortex, and left hippocampus compared to other groups (p ≤ 0.05, corrected). No significant effect was found regarding anatomical or non-olfactory ROIs GMV. The left hippocampus olfactory ROI GMV was correlated with episodic memory performance (p < 0.05 corrected). Limbic/medial-temporal olfactory processing areas are specifically atrophied at the MCI stage, and the degree of atrophy might predict cognitive decline in AD early stages.

This longitudinal study aimed to evaluate qualitative (parosmia) and quantitative (hyposmia/anosmia) olfaction 2–4 weeks (baseline) and 6 months (follow-up) after a mild traumatic brain injury (mTBI). We further evaluated the predictive value of baseline depression, anxiety, and olfaction scores on depression and anxiety at follow-up. At baseline, olfactory function and affective state were assessed in 107 participants (53 patients with mTBI; 54 healthy controls). At follow-up, data were collected on 71 participants (32 patients and 39 controls). Both at baseline and follow-up, patients with mTBI showed more signs of parosmia, depression, and anxiety compared with controls. However, patients did not, neither at baseline nor follow-up, show quantitative olfactory impairment. Moreover, although baseline scores of depression and anxiety helped predict the development of symptoms of depression and anxiety at follow-up, adding parosmia scores to the prediction model significantly increased the amount of explained variances. Clinicians should implement affective and olfactory evaluation to predict patients’ affective outcome.

Episodic memory deficit is a symptom frequently observed after a mild traumatic brain injury (mTBI). However, few studies have investigated the impact of a single and acute mTBI on episodic memory and structural cerebral changes. To do so, we conducted two experiments. In the first, we evaluated verbal episodic memory by using a word recall test, in 52 patients with mTBI (mean age 33.1 [12.2] years) 2–4 weeks after a first mTBI, compared with 54 healthy controls (31.3 [9.2] years) and followed both groups up for 6 months. In the second, we measured hippocampal volume in a subset of 40 participants (20 patients with mTBI, 20 controls) from Experiment 1 using magnetic resonance imaging (MRI; T1-weighted images) and correlated memory performance scores to hippocampal volume. Experiment 1 showed significantly reduced verbal episodic memory within the first month after an mTBI and a tendency for a reduction 6 months later, more pronounced for men. In Experiment 2, patients with mTBI exhibited a generally reduced hippocampal volume; however, we did not observe any linear correlation between hippocampal volume and memory scores. These results suggest that one single mTBI is associated with both episodic memory alteration and reduced volume of the hippocampus in the acute phase. Future studies are needed to elucidate the link between both measures.