The team of Shandong Provincial Hospital established the association between olfactory impairment and AD-derived MCI for the first time!

This study not only established an association between the occurrence of two major subtypes of olfactory dysfunction and MCI, but also found that the severity of olfactory impairment was clearly related
to cognitive decline, elevated biochemical markers, and the degree of change in corresponding imaging markers.

Bad nose? It's not rhinitis, it may be that cognitive function is going to be a problem!

Everyone should be familiar with Alzheimer's disease (AD), but many people may be relatively new to
mild cognitive impairment (MCI).
In this article, we will start
with MCI.

When you are older, it is easy to forget things and memory loss, which is a natural law, and immortals have no way
.
Many people have relatively mild symptoms, which affect but do not completely affect daily life, and there is not much problem with self-care; The disease is severe to a certain extent called dementia, and the most important type of dementia is the familiar AD
.

But then again, sudden decline in cognitive function is rare, and symptoms in AD patients are gradual.

Later, a consensus was formed that the stage of cognitive status below the normal level of current age and between preclinical and dementia was called MCI (below).

MCI is further divided into amnesic mild cognitive impairment (aMCI) and non-amnesic mild cognitive impairment (naMCI)
based on memory impairment.

Schematic diagram of changes in cognitive function over time during normal aging and AD

Because AD is difficult to detect in the preclinical stage, and there is a lack of effective treatment after diagnosis, many scientists focus on MCI-related research, hoping to intervene in the progress of AD in advance at this stage and prevent some patients from entering the AD stage
.
Unfortunately, because the diagnosis of MCI relies on cumbersome cognitive function tests and lacks landmark symptoms, signs and results, it is difficult
to accurately identify MCI patients.

Recently, a research team led by Du Yifeng and Wang Yongxiang of the Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital) published the latest research results
in the famous journal Alzheimer's & Dementia.

They combined large clinical data, laboratory and imaging results and found that olfactory dysfunction was clearly associated with the development of MCI, and that there was a correlation with biochemical markers and imaging markers associated with cognitive decline [1].

Although there is previous evidence that olfactory disturbance is strongly associated with the onset of AD, and symptoms appear earlier [2]; However, this study establishes for the first time the exact association between the symptoms of olfactory disorder and AD-derived MCI, which not only brings new ideas for identifying individuals with MCI, but also brings a new entry point
to the sense of smell for early intervention of MCI and even AD.

Screenshot of the paper

The study included a total of 4214 elderly people in rural areas, with an average age of 70.
9 years
.
Of these, 1102 (26.
2%) were diagnosed with MCI, of which 931 were aMCI and 171 were naMCI
.

The researchers compared baseline levels in the normal population with those with MCI and found that the MCI group had a higher mean age, a higher proportion of women, a higher proportion of stroke, lower levels of education, lower body mass index (BMI), and lower rates of smoking and drinking alcohol (below).

Comparison of baseline levels in the normal population and the MCI population

In terms of olfactory and cognitive function, the two groups showed significant differences
.

The overall olfactory rod identification experiment (SSIT) score in the MCI group was significantly lower than that in the control group, suggesting that the overall olfactory function was worse in the MCI group and the proportion of olfactory loss was higher
.

In addition, in all areas of cognitive function testing, patients in the MCI group scored significantly lower
.

Comparison of cognitive function in normal and MCI populations

That being the case, is olfactory disturbance really associated with the onset of MCI? The researchers explored the correlation
between the two using two models.

First, with the same demographic characteristics, a high SSIT score (with a sharper sense of smell) had an OR value of 0.
88 for MCI, 0.
87 for aMCI, and 0.
90
for naMCI.
Since OR values less than 1 indicate a protective effect, this means that the more normal olfactory function, the lower
the risk of developing aMCI and naMCI.

On the other hand, the risk of MCI, aMCI, and naMCI was significantly higher
in the hypoolfactory and anofactory loss groups compared with the normal olfactory group.
At the same time, the results were statistically significantly different
when controlling for APOE genotype, lifestyle, metabolism, and other clinical factors.
These results further establish an association
between olfactory disturbance and the development of MCI.

The relationship between olfactory disturbance and the risk of developing MCI in two models

These associations are based on clinical evaluations of cognitive and olfactory functions
.
Does this association persist in ancillary tests, such as laboratory tests and imaging tests?

To clarify this problem, the researchers first compared plasma biochemical marker levels in MCI populations (n=315) and non-MCI populations in a subgroup analysis of biochemical markers (n=1054), and then used the above two models to explore possible correlations
.

The results showed no correlation
between SSIT scores and Aβ40, Aβ42, and Aβ40/Aβ42.
However, high SSIT scores were significantly associated with low plasma t-tau and NfL in both models, particularly in the presence of anosmia
.
In addition, elevated levels of t-tau and NfL were linearly correlated with the severity of olfactory impairment and were statistically significant in both models (P for trend <0.
01).

This result suggests that olfactory disturbance is associated
with changes in AD biochemical markers.

Association of olfactory disturbances with changes in biochemical markers of AD

On the other hand, in imaging subgroup analysis using MRI (n=917, of which 218 were MCI), they found that the volume of cortex in the hippocampus and endoolfactory zone, as well as the cortical thickness of AD-related areas, was significantly reduced in the MCI group, and the volumes of white matter hyperintensity (WMH) and paraventricular white matter hyperintensity (PWMH) were higher than in the control group
.

Further analysis showed that high SSIT scores were positively correlated with hippocampal volume and negatively correlated
with WMH and PWMH.
Similar to the results of biochemical markers, loss of smell was clearly associated with decreased cortical volume in the hippocampus and enolfactory zone, as well as elevated WMH and PWMH
.

Association of olfactory disturbances with imaging markers

In addition, the researchers also found that the effect of SSIT score on cortical volume in the enolfactory zone is age-dependent
.
The positive correlation between high SSIT scores and cortical volume in the olfactory zone was more pronounced in people over 75 years of age and absent in people under 75 years of age
.

In summary, olfactory loss is closely related to imaging indicators related to cognitive decline, and the more obvious
this correlation is with the age of the patient.

Effect of olfactory disturbance on cortical volume in the enolfactory zone at different ages

Overall, this study not only established an association between the occurrence of two major subtypes of olfactory dysfunction and MCI, but also found that the severity of olfactory impairment was clearly correlated
with cognitive decline, elevated biochemical markers, and the degree of corresponding imaging marker changes.

In addition, since t-tau and NfL are related to the pathological features of AD, amyloid plaque and nerve fiber tangles, respectively, and the main cause of WMH and PWMH formation is cerebral small vessel disease, the relationship between olfactory dysfunction and the above markers suggests that pathological changes in AD and cerebral small vessel lesions may be common mechanisms
for olfactory loss and cognitive decline.

Therefore, olfactory disturbance is likely to become a clinical marker
in the early stage of AD in the elderly population.
Admittedly, this conjecture needs to be supported by more clinical and basic research evidence, but I believe that with the unremitting efforts of scientists, the mystery of the relationship between olfactory impairment and cognitive decline will be gradually solved, let's
wait and see.

References:

1.
Dong, Yi, et al.
"Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults.
" Alzheimer's & Dementia.

2.
Doty, Richard L.
"Olfactory dysfunction in neurodegenerative diseases: is there a common pathological substrate?.
" The Lancet Neurology 16.
6 (2017): 478-488.