Researchers of this Mendelian randomisation study set out to examine whether there is an association between lean mass (genetically proxied) and increased risk of Alzheimer’s disease. As there is no cure for Alzheimer's, the identification of modifiable risk factors has become a cornerstone of the efforts to manage the impacts of the disease. 
 

Existing studies have found a positive correlation between obesity and an increased risk of Alzheimer's, but prior to this research, there had been no high-quality studies which considered the impact of different measures of body composition, such as lean mass, on the risk profile of the disease.
 

Lean mass is defined as the difference between total mass and fat mass. It is used as a proxy for muscle mass and has been found to be consistently reduced in patients with Alzheimer's disease. However, the direction of this effect has yet to be definitely determined. The researchers therefore, quantified their main outcome measure as the effect of genetically proxied lean mass on the risk of Alzheimer's disease and the related phenotype of cognitive performance

The study utilized summary-level genetic data from various sources, including:

• Data from 450,243 participants in the UK Biobank, who had measurements of both lean mass and fat mass using impedance measures

• An independent sample comprising 21,982 patients diagnosed with Alzheimer's disease and 41,944 individuals without Alzheimer's disease serving as controls

• A replication sample involving 7,329 patients with Alzheimer's disease and 252,879 control subjects

• Genetic data from 269,867 individuals who participated in a genome-wide association study focused on cognitive performance

In summary, the results showed: 

• An increase in genetically proxied appendicular lean mass of one standard deviation was associated with a 12% reduced risk of Alzheimer’s 

• This finding was replicated in an independent cohort of patients with Alzheimer’s disease 

• Higher genetically proxied appendicular lean mass was also associated with increased cognitive performance 

• Similar results were found for the outcomes of Alzheimer’s disease and cognitive performance when the risk factors of genetically proxied trunk lean mass and whole body lean mass were used, respectively, and adjusted for genetically proxied fat mass.

The researchers conclude that these findings suggest that lean mass may indeed be a modifiable factor in mitigating the development of Alzheimer's. These findings' clinical and public health implications cannot be overstated, and further investigations should be prioritised.