This assessment of 286 MCI participants enrolled in ADNI suggests that lower BMI at baseline is associated with increased rates of cognitive decline over 1 year as measured by the MMSE, ADAS-Cog, and a global composite score derived from the ADNI neuropsychologic battery. Lower BMI was also associated with increased risk of clinically significant decline on the MMSE and ADAS-cog suggesting that these associations are clinically recognizable and important. The data indicate that BMI remained stable through this short follow-up whereas cognition declined, suggesting that low BMI predisposes an individual to more rapid disease progression. Alternatively, factors associated with MCI and cognitive decline may influence body composition. Longer follow-up with time-lagged or change-score designs in the ADNI sample is warranted to investigate the causal relationship between weight loss and cognition.
BMI is a commonly used measure of adiposity that is associated with adverse health outcomes including mortality,18–20
Several longitudinal studies have demonstrated that lower BMI at baseline and loss of BMI over time is associated with an increased risk of developing AD.10,11,27,28
Individuals who develop dementia have weight loss in the 4 to 10 years leading up to diagnosis with accentuation of this weight loss at the time of diagnosis, depending on diagnostic criteria.10,11
Although clinical studies suggest that weight loss may be present in the clinical and preclinical stages of AD, autopsy data suggests that the loss of BMI in older adults may be in part related to the accumulation of AD pathology.29
In a clinical-pathologic study of 298 individuals, BMI in the years before death was associated with AD pathologic burden, even in nondemented individuals.29
As many, if not most, individuals with MCI are in the earliest clinical stages of AD,30,31
our data is consistent with prior studies suggesting that decreased BMI may be an early systemic manifestation of the AD process.10,27,28
In this study, however, BMI did not predict progression to a diagnosis of AD, although the power to assess this relationship is limited by the small number of individuals progressing to AD (n=54) over the short time frame (1 y). This issue is likely compounded by the subjectivity of the diagnostic appreciation across centers and individual clinicians.
Although MCI is a heterogeneous condition and can be related to static or reversible causes (ie, depression, medications, and medical illness), the MCI criteria identify a population enriched with individuals in the earliest clinical stages of AD. Although our analyses did not demonstrate increased rates of progression to overt clinical AD, the relationship between BMI and cognitive decline is consistent with prior studies suggesting that AD neuropathology, which likely begins accumulating years before the clinical onset, may be in part responsible for lower BMI.27
Greater atrophy in the medial temporal lobe in AD is associated with lower BMI suggesting that brain change and body weight occur in tandem.32
Psychosocial hypotheses for weight loss such as behavioral changes influencing caloric intake (forgetting to eat or the inability to plan and prepare adequate meals) are possible, although the studies suggest against this possibility10,33
and MCI participants have limited functional changes.
This study is limited by a short follow up period of 1 year attenuating our power to assess the impact of BMI on cognitive decline in MCI and subsequent progression of MCI to AD. Although the overall effect reported here is modest, the time period measured is short (1 y) and given the likelihood of cumulative cognitive decrements, the long-term clinical impact on cognition may be severe. Thus, the findings reported here are confined to associations with the baseline BMI and not with change in BMI over time. In addition, BMI does not differentiate the contributions from muscle mass and body fat; thus, low BMI may reflect reductions in muscle mass, fat mass, or both. Further differentiating the role of body composition using more sensitive measures that differentiate components of body composition may be important given that muscle and fat are metabolically different and have different risk implications. Future studies should explore the use of more sophisticated measures of body composition to characterize the individual relationships of lean mass and fat mass on cognitive decline through time.