Energy intake and expenditure in patients with Alzheimer’s disease and mild cognitive impairment: the NUDAD project

Doorduijn, Astrid S.; Schueren, Marian A.E. de van der; Rest, Ondine van de; Leeuw, Francisca A. de; Hendriksen, Heleen M.A.; Teunissen, Charlotte E.; Scheltens, Philip; Flier, Wiesje M. van der; Visser, Marjolein

doi:10.1186/s13195-020-00687-2

Cited by 25 publications

(21 citation statements)

References 37 publications

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“…Since AD patients tend to lose weight over the course of the disease, it has been suggested that cognitive decline could lead to lower energy intake which might also affect microbiota composition ( 51 ). However, we have found previously that macronutrient intake was not different between diagnosis groups in this cohort ( 52 ). Moreover, associations between gut microbiota composition and AD biomarkers remained significant when adjusting for cognitive function (MMSE).…”

Section: Discussioncontrasting

confidence: 51%

Gut Microbiota Composition Is Related to AD Pathology

et al. 2022

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IntroductionSeveral studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Materials and MethodsWe included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE.ResultsThe machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis, and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status.ConclusionsGut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.

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Section: Discussioncontrasting

confidence: 51%

Gut Microbiota Composition Is Related to AD Pathology

et al. 2022

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“…There is some controversy over contribution of energy expenditure on metabolic deficits in AD patients. While some studies show increased metabolism in AD [53], others indicate decreased or non-significant changes in energy expenditure (EE) in AD patients [54]. As previously seen, the Tg4510 and 3xTg mouse models of AD show a hypermetabolic state at an early age [13,46,55].…”

Section: Alterations In Food Intake and Energy Expenditure In 5xfad Micementioning

confidence: 87%

A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse

López-Gambero

Rosell‐Valle

Medina-Vera

et al. 2021

IJMS

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Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer’s disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.

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“…In line with this notion, we recently found a higher resting energy expenditure in patients with AD dementia compared with controls. 47 Future studies should further examine the potentially higher energy needs of patients with AD dementia.…”

Section: Discussionmentioning

confidence: 99%

Nutritional Status Is Associated With Clinical Progression in Alzheimer's Disease: The NUDAD Project

Doorduijn

Schueren

Rest

et al. 2023

Journal of the American Medical Directors Association

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Objective: In cognitively normal adults, nutritional parameters are related to cognitive decline and incidence of dementia. Studies on the role of nutrition in predementia stages subjective cognitive decline and mild cognitive impairment, and mild stages of Alzheimer's disease (AD) dementia in a clinical setting are lacking. In the absence of a curative treatment, this evidence is important for targeting nutritional factors to potentially prevent or delay further cognitive decline. Our aim is to investigate associations of nutritional parameters with clinical progression in patients ranging from those who are cognitively normal to those who have AD dementia. Design: Longitudinal. Setting and Participants: Memory clinic, 551 patients (219 with subjective cognitive decline, 135 with mild cognitive impairment, and 197 with AD dementia), mean age 64 AE 8 years. Measurements: We assessed body mass index, fat-free mass, Mini-Nutritional Assessment, and dietary intake with the Dutch Healthy Diet food frequency questionnaire and the 238-item healthy life in an urban setting (HELIUS) food frequency questionnaire at baseline. Cox proportional hazard models were used to evaluate associations of nutritional parameters with clinical progression. Additional analyses were restricted to patients who were amyloid positive. Results: We observed clinical progression in 170 patients (31%) over 2.2 AE 0.9 years. Poorer Mini-Nutritional Assessment score [hazard ratio (95% confidence interval) 1.39 (1.18e1.64)], lower bodyThe NUDAD project is funded by NWO-FCB (project number 057-14-004) and AD, FdL and HH are appointed on this project. The sponsors had no role in the design, methods, participant recruitment, data collections, analysis, and preparation of the report. AD, MdvdS, OvdR, FdL, HH, and MV have no potential conflicts of interest. PS has served as consultant for Wyeth-Elan, Genentech, Danone, and Novartis. CT is a member of the

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Energy intake and expenditure in patients with Alzheimer’s disease and mild cognitive impairment: the NUDAD project

Cited by 25 publications

References 37 publications

Gut Microbiota Composition Is Related to AD Pathology

Gut Microbiota Composition Is Related to AD Pathology

A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse

Nutritional Status Is Associated With Clinical Progression in Alzheimer's Disease: The NUDAD Project

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