Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer's disease

Jiménez, Amanda; Pegueroles, Jordi Malé i; Carmona-Iragui, María; Vilaplana, Eduard; Montal, Víctor; Alcolea, Daniel; Videla, Laura; Illán-Gala, Ignacio; Pané, Adriana; Casajoana, Anna; Belbin, Olivia; Clarimón, Jordi; Moizé, Violeta; Vidal, Josep; Lleó, Alberto; Fortea, Juan; Blesa, Rafael

doi:10.18632/oncotarget.22218

Cited by 60 publications

(58 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a cohort of healthy elderly individuals, faster cognitive decline and accelerated atrophy rate were observed in those with relative weight loss greater than or equal to 5% (equivalent to greater than or equal to 1.2% annual loss) compared with those with relative weight loss less than 5% (equivalent to less than 1.2% annual loss). 44 Similarly, a Norwegian study that assessed percent change in BMI in midlife reported that while greater than or equal to 5% loss (equivalent to approximately greater than or equal to 0.6% annual loss) was associated with increased risk of dementia-related mortality, a gain of greater than or equal to 20% (equivalent to approximately greater than or equal to 2.2% annual gain) was associated with reduced risk. 45 Conversely, for vascular dementia, weight gain was associated with a modest 20% increased risk but only in those aged younger than 60 years at study baseline.…”

Section: Discussionmentioning

confidence: 99%

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta‐analysis consisting 2.8 million adults with 57 294 cases of dementia

et al. 2020

View full text Add to dashboard Cite

Summary Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta‐analysis. Compared with body mass index–defined lower‐normal weight (18.5‐22.4 kg/m2), the risk of all‐cause dementia was higher among underweight individuals but lower among those with upper‐normal (22.5‐24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all‐cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non‐linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta‐analysis consisting 2.8 million adults with 57 294 cases of dementia

et al. 2020

View full text Add to dashboard Cite

show abstract

“…1 shows the study flow-chart. We and others have previously showed that unintentional weight loss may represent a non-cognitive sign of AD [29][30][31] and a confounder in the relationship between obesity and brain structure [9]. Therefore, we excluded those participants with significant weight loss (i.e weight change > 5% from baseline weight) in throughout follow-up (n = 43), and those with a personal history of bariatric procedures (n = 3).…”

Section: Study Participantsmentioning

confidence: 99%

“…On the contrary, the only two previous longitudinal studies showed greater amyloid deposition late in life in relation with mid-life obesity [15,16] Discrepancies between mid-life and late-life studies might be explained by reverse causation (i.e. AD related weight loss in preclinical AD), selection and survival biases (i.e higher mortality and dementia risk in persons with obese might determine that only those specially protected against obesity consequences survived or/and maintained normal cognition late in life) or by the existence of additive and/or competing risk (i.e obesity not only promote neurodegeneration throughout AD pathophysiological mechanisms and therefore only those with lower AD burden remain cognitively normal late in life) [9,29,30,43]. In order to minimize the confounding effect of weight loss on the impact of obesity on the different biomarkers, we excluded those subjects with significant weight loss [9,30].…”

Section: Tuulari Et Al and Rebelos Et Al Did Not Observe Differencementioning

confidence: 99%

Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly

Pegueroles

Pané

Vilaplana

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Mid-life obesity is related to increased risk for overall dementia and Alzheimer´s disease (AD) dementia. In the present work, we aimed to investigate the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) biomarkers of amyloid (Aβ 1-42) and tau-pathology (total-tau and p-tau) in healthy elderly. Methods: We selected healthy controls from ADNI2 with available CSF AD biomarkers and/or fluorodeoxyglucose (FDG) PET and 3T-MRI. Participants without follow-up or with significant weight loss were excluded from the analyses. Brain cortical thickness (Cth) was evaluated with Freesurfer software and FDG uptake was measured with a surface-based method using both SPM and Freesurfer softwares. We performed regression analyses between FDG uptake, CTh, CSF AD biomarkers levels and BMI and interaction analyses with age by obesity/overweight status. Results: We included 147 individuals (mean age 73.3 years, mean BMI 27.4 Kg/m 2 ). Higher BMI was related to less cortical thickness and higher glucose metabolism in brain areas not typically involved in AD (FWE<0.05), with little overlap between them. There was no association between BMI and any of the CSF core AD biomarkers. The relationship between age and brain metabolism was modified by overweight/obesity status, but not that of age and brain structure or core CSF AD biomarkers. Conclusions: Our data support that obesity has differential effects on brain metabolism and structure independent of an underlying AD pathophysiology in cognitively unimpaired elderly.

show abstract

“…Obesity is considered a risk factor for AD [1][2][3]. However, the relationship between body weight and dementia appears complex [4][5][6], and recent observations even pose a protective role of late-life excess weight in AD [7]. Taking into account the worrying worldwide prevalence of obesity and dementia [8,9], greater knowledge of possible links between the two conditions is imperative.…”

Section: Introductionmentioning

confidence: 99%

Circulating insulin-like growth factor I is involved in the effect of diet on peripheral amyloid β clearance

Herrero-Labrador

Trueba-Saiz

Martinez-Rachadell

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundObesity is a risk factor for Alzheimer´s disease (AD), but underlying mechanisms are not clear.MethodsWe analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact on brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance, and is increased in serum of overweight mice. Results Overweight mice showed increased peripheral Aβ clearance by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. We also found that Aβ clearance by hepatocytes is stimulated by IGF-I, and that mice with low serum IGF-I levels show reduced peripheral Aβ clearance and unchanged brain Aβ levels. In the brain, IGF-I favored association of its receptor (IGF-IR) with Aβ precursor protein (APP), and at the same time stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly reduced brain IGF-IR phosphorylation and APP/IGF-IR association was found in overweight mice as compared to lean controls. Conclusions Collectively, these results indicate that diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ clearance probably because its brain entrance is reduced.

show abstract

Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer's disease

Cited by 60 publications

References 47 publications

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta‐analysis consisting 2.8 million adults with 57 294 cases of dementia

Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta‐analysis consisting 2.8 million adults with 57 294 cases of dementia

Obesity impacts brain metabolism and structure independently of amyloid and tau pathology in healthy elderly

Circulating insulin-like growth factor I is involved in the effect of diet on peripheral amyloid β clearance

Contact Info

Product

Resources

About