Alz Res Therapy: weight loss, or may predict pathological changes in AD

Weight loss is common in Alzheimer's disease (AD) patients and is related to the progression and severity of the disease
.

Evidence from long-term longitudinal epidemiological studies has shown that weight loss lasts ten years or more before the onset of dementia and accelerates at the time of diagnosis

Regarding the mechanism of these associations, some people believe that hypothalamic dysfunction and olfactory function impairment are due to AD-related neurodegeneration (or in the context of other neurodegenerative diseases) that may lead to weight loss
.

According to this view, it is not so much the cause of AD as weight loss is a clinical manifestation that may appear before cognitive impairment occurs

In addition, the cognitive, behavioral, and emotional changes that occur during the course of the disease may also cause weight loss
.

In the past few years, studies incorporating AD biomarkers have shown a higher baseline level of amyloid β (Aβ) deposition measured by positron emission tomography (PET) and a higher ratio of tau/Aβ42 in cerebrospinal fluid (CSF) Levels are associated with greater prospective weight loss, and a recent study reported a negative correlation between changes in BMI and the burden of amyloid β-PET
.

Other studies have found a negative correlation between BMI and the deposition of Aβ and tau in the brains of elderly people without cognitive impairment
.

Although these studies have focused on the association with the continuous measurement of AD biomarkers, few studies have used classification results, such as the visual reading results of amyloid-PET, to assess whether weight loss can predict the positivity of AD biomarkers

Determining the extent to which weight change predicts the outcome of AD biomarkers may be meaningful for evaluating weight loss as a potential predictor of cognitive impairment caused by AD
.

In addition, analyzing the differences in weight changes between adults without cognitive impairment with different biomarker characteristics may help clarify when weight loss occurs during the preclinical continuous process, which is currently unclear
.

Finally, whether previous studies have assessed the association between weight change and biomarkers of axon damage and synaptic dysfunction, such as neurofilament light chain (NfL) and neurogranin, which are thought to occur in amyloid and Downstream of tau deposition
.

Exploring these associations may help determine the characteristics of biological changes associated with weight loss in preclinical AD

In this way, Oriol Grau-Rivera of Barcelona Beta Brain Research Center (BBRC) and others investigated the extent to which previous weight loss can predict amyloid positron emission tomography in cognitively accessible middle-aged people ( PET) results of visual readings and cerebrospinal fluid (CSF) AD biomarkers
.

The secondary objectives are to (i) analyze the differences in weight changes of individuals with different CSF biomarker characteristics, (ii) describe the association of weight changes with continuous measurements of CSF and PET biomarkers and longitudinal changes in cognitive performance, and ( iii) Explore whether these associations are changed by amyloid β (Aβ) status, family history of AD, and age

They found that weight loss indicates a higher probability of FTM-PET positive (OR 1.

27, 95% CI 1.
00-1.

Weight change is positively correlated with the CSF Aβ42/40 ratio (β = 0.
099, p = 0.
032), and CSF p-tau (β =-0.
141, p = 0.
005), t-tau (β =-0.
147 p = 0.
004) and neurogranin The level (β =-0.
158, p = 0.
002) is negatively correlated
.

In the stratified analysis, weight loss was significantly associated with higher t-tau, p-tau, neurofilament and neurogranin, and only the A+ participants had a faster cognitive decline
.

The important significance of this study lies in the discovery that weight loss can predict the results of AD CSF and PET biomarkers, and may occur downstream of preclinical AD amyloid β accumulation, which coincides with cognitive decline
.

Therefore, it should be regarded as an indicator of the increased risk of AD-related cognitive impairment

Association of weight change with cerebrospinal fluid biomarkers and amyloid positron emission tomography in preclinical Alzheimer's disease

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