Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease

Abstract

Weight changes are common in aging and Alzheimer’s disease (AD) and post-mortem findings suggested a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF) based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ1-42), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF−). Results showed that BMI was significantly lower in the CSF+ when compared to the CSF− group (F = 27.7, df = 746, p < 0.001). There was no interaction between CSF signature and diagnosis or ApoE genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and non-demented elderly subjects.

Low Plasma Leptin in Cognitively Impaired ADNI Subjects: Gender Differences and Diagnostic and Therapeutic Potential

“…The NC and MCI groups had significantly higher MMSE scores compared to those of the AD group. The mean body mass index (BMI) was lower in MCI and AD cohorts, significantly so for the latter compared to NC (Table 1), as reported previously [29]. Baseline plasma leptin values were significantly lower in the MCI group, compared to NC and while lower in the AD subjects, values were not significantly different from MCI subjects (Table 1), in agreement with previous studies [16, 17, 30].…”

“…Our cross-sectional observations imply that plasma leptin levels in MCI men and possibly non-obese women are different to those predicted by BMI values in NC. Thus, leptin as a marker could strengthen the predictive power of low BMI which has been consistently linked to disease onset [29, 35, 36], and associated with biological markers of core brain pathology of AD [29]. The present data suggest but do not prove that for both genders, the decline in circulating leptin itself may have a role in the cascade of AD causation.…”

CSF biomarkers of Alzheimer disease

“…A cross-sectional study found that abnormal CSF levels of Ab 42 and tau were associated with lower body mass index in a sample comprising individuals with and without memory problems (i.e., were cognitively normal, had MCI, or had AD dementia), 20 consistent with a possible link between abnormal AD biomarker levels and weight loss. A literature review did not reveal any prior studies that examined biomarkers as a predictor of future weight loss among cognitively normal individuals.…”

Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology

“…The appreciation that AD pathology develops decades prior to the initial cognitive symptoms suggest that the late-life changes in body weight may reflect the earliest stage of the disease process [40,46]. Supporting this notion, low BMI is associated with worsening AD pathology in postmortem brains [47,48] as well as worsening CSF biomarkers (tau and Aβ1–42) [49]. Collectively, these studies suggest that increased adiposity during midlife contribute or influence the risk of developing age-related dementia, while reduced adiposity in late-life is an early consequence of the disease and may contribute to its progression.…”