Olfaction in patients with mild cognitive impairment and Alzheimer's disease

Djordjević, Jelena; Jones‐Gotman, Marilyn; Sousa, Kathy De; Chertkow, Howard

doi:10.1016/j.neurobiolaging.2006.11.014

Cited by 329 publications

(275 citation statements)

References 46 publications

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“…Recent advances in imaging techniques confirmed previously described postmortem changes by providing evidence for reductions in fMRI signal intensities in the primary olfactory cortex, hippocampus and insula that were significantly correlated with olfactory impairments and cognitive decline in AD patients (Wang et al, 2010). These findings are also in line with the consistent olfactory deficits during pre-clinical stages of AD (Peters et al, 2003, Djordjevic et al, 2008, that appear to be highly predictive for the conversion from mild cognitive impairment (MCI) to AD (Devanand et al, 2000). Importantly, MCI patients carrying the ApoE ε4 allele , as well as cognitively normal elderly ε4-carriers showed significantly poorer odor identification than those without an inherited ε4 allele.…”

Section: Olfactory-limbic Pathways and Adsupporting

confidence: 74%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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Alzheimer's disease (AD) is one of the largest unmet medical concerns of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles, the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiological characteristic of late-onset AD. AbstractAlzheimer`s disease (AD) is one of the largest unmet medical needs of our society. Around 25 million patients worldwide together with their families are still waiting for an effective treatment. We have recently initiated a re-evaluation of our knowledge of the molecular and cellular mechanisms underlying sporadic AD. Based on the existing literature, we have proposed a mechanistic explanation of how the late-onset form of the disease may evolve on the cellular level. Here, we expand this hypothesis by addressing the pathophysiological changes underlying the early and almost invariant appearance of the neurofibrillary tangles (NFTs), the only reliable correlate of the cognitive status, in distinct brain areas and their consistent "spread" along interconnected neurons as the disease advances. In this review we present and discuss novel evidence that the extracellular signaling protein Reelin, expressed along the olfactory and limbic pathways in the adult brain, might hold a key to understand the earliest steps of the disease, highlighting the olfactory pathway as the brain's Achilles heel involved in the initiation of the pathophysiology characteristic of late-onset AD.3

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Section: Olfactory-limbic Pathways and Adsupporting

confidence: 74%

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

et al. 2013

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“…The statistical analysis using polyserial method showed 0.3650, 0.2967 and 0.3313 as the correlation coefficient in male, female and all-comers, respectively, suggesting weak correlation between olfactory function and cognitive function. It seems to be reasonable because there might be a time-lag between the initiation of olfactory impairment and that of mental decline [11,[23][24][25][26]. Table 1 indicates the age categories firstly showing the smell loss (defined as less than 3) and mental decline (defined as less than 28) are 70-79 (2.65) and 80+ (27.6), respectively.…”

Section: Participants Characteristics and Test Resultsmentioning

confidence: 99%

Olfactory function evaluation in a 1102 community-dwelling 20-90-year old Japanese population in relation with age, sex and mental decline

Yanagimachi¹,

Takahashi²,

Bernier³

et al. 2017

Alzheimers Dement Cogn Neurol

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Purpose: Decline of olfactory function has been linked to aging of the brain and also to risk of developing dementia and other neurodegenerative diseases according to several Western studies of community-dwelling populations. The aim of this study was to understand the usefulness of a smell identification test to identify early signs of mental decline in relation with age, sex, and education in a community-dwelling population in Japan. Material and methods:The participants comprised of 1102 volunteers aged 20-90 (437 male and 665 female) who entered the Hirosaki University observational longitudinal study that first started in 2005. Each participant self-evaluated their olfactory abilities and later on were subject to modified Pocket Smell Test (mPST) odor identification test developed in collaboration with Sensonics Inc. followed by the Mini Mental State Examination (MMSE) to evaluate mental fitness. Multiple statistical analyses were performed to determine the usefulness of the simplified 4-odor (grape, onion, rose and soap) to understand non-invasively possible deterioration of brain function in relation with self-estimation of olfactory function, subjects age, sex, education and MMSE. Results:The results revealed similarities between self-estimation of olfactory sensory capabilities and mPST odor identification test (82.2% accuracy). A clear relationship between aging, sex, education and olfactory system impairment was also observed. In addition, the polyserial correlation coefficient was 0.3313, suggesting the association between olfactory impairment and decline of mental fitness. Thus, mPST appears useful to detect an early decline of mental fitness in Japanese general population.

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“…Also, the olfactory identification deficits together with lack of awareness of the olfactory deficits in MCI patients predicted conversion to AD in a three-year follow-up study where patients were followed at six-month intervals. Djordjevic, Jones-Gotman, De Sousa, and Chertkow (2008) replicated and extended these findings by demonstrating that MCI patients show deficits in three olfactory domains: olfactory thresholds, discrimination, and identification. Regarding the impact of olfactory sensitivity (i.e., thresholds) in AD progression evidence is mixed.…”

Section: Olfactory Function In MCI and Dementiamentioning

confidence: 59%

“…Regarding the impact of olfactory sensitivity (i.e., thresholds) in AD progression evidence is mixed. Some studies suggest that an olfactory threshold impairment precedes the AD diagnosis Djordjevic et al, 2008), and that increased olfactory thresh-olds in patients with AD reflect the effects of the disease process (Morgan et al, 1995;Murphy, Gilmore, Seery, Salmon, & Lasker, 1990;Nordin, Almkvist, Berglund, & Wahlund, 1997). Others report of no odor threshold impairment in the preclinical stage, suggesting that the selective odor identification deficit reflects that the olfactory impairment in AD is central rather than peripherally driven (Koss et al, 1988;Larsson et al, 1999;Serby, Larson, & Kalkstein, 1991).…”

Section: Olfactory Function In MCI and Dementiamentioning

confidence: 99%

Olfactory Function: The Influence of Demographic, Cognitive, and Genetic factors

Hedner¹

2013

PsycEXTRA Dataset

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Olfactory function is affected by demographic, cognitive, and genetic factors. In the present thesis, three empirical studies investigated individual differences in olfactory ability. Study I explored demographic and cognitive correlates in common olfactory tasks; odor detection, odor discrimination, and odor identification. The results indicated that old age influenced performance negatively in all tasks, and that semantic memory proficiency and executive functioning were related to odor discrimination and odor identification performance. No cognitive influence was observed for measurements of olfactory threshold. Using population-based data, Study II investigated a potential influence of the ApoE gene on olfactory identification after controlling for health status, semantic memory, and preclinical and clinical dementia. The main finding was that the ApoE-ɛ4 allele interacted with age, such that older ɛ4-carriers had an impaired odor identification performance relative to older non-carriers. Importantly, the negative ApoE-ɛ4 effect on olfactory proficiency was independent of clinical dementia conversion within five years. Study III investigated the effects of the BDNF val66met polymorphism on olfactory change over a five-year interval, in a communitydwelling sample of young and old age cohorts. The results showed that agerelated decline in olfactory identification was influenced by the BDNF val66met. In middle-aged subjects, no effect of BDNF val66met was observed although older val homozygote carriers showed a selectively larger olfactory decline than the older met carriers. Overall, results suggest that the relative influence of demographic and cognitive factors vary across different olfactory tasks and that two genes (ApoE and BDNF) impact age-related deficits in odor identification. Potential theoretical and practical implications of the findings are discussed as well as potential limitations of association studies in genomics research.

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Olfaction in patients with mild cognitive impairment and Alzheimer's disease

Cited by 329 publications

References 46 publications

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Decisive role of Reelin signaling during early stages of Alzheimer’s disease

Olfactory function evaluation in a 1102 community-dwelling 20-90-year old Japanese population in relation with age, sex and mental decline

Olfactory Function: The Influence of Demographic, Cognitive, and Genetic factors

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