Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.

Stress exposure during the sensitive period of early development has been shown to program the brain and increases the risk to develop cognitive deficits later in life. We have shown earlier that early-life stress (ES) leads to cognitive decline at an adult age, associated with changes in adult hippocampal neurogenesis and neuroinflammation. In particular, ES has been shown to affect neurogenesis rate and the survival of newborn cells later in life as well as microglia, modulating their response to immune or metabolic challenges later in life. Both of these processes possibly contribute to the ES-induced cognitive deficits. Emerging evidence by us and others indicates that early nutritional interventions can protect against these ES-induced effects through nutritional programming. Based on human metabolomics studies, we identified various coffee-related metabolites to be part of a protective molecular signature against cognitive decline in humans. Caffeic and chlorogenic acids are coffee-polyphenols and have been described to have potent anti-oxidant and anti-inflammatory actions. Therefore, we here aimed to test whether supplementing caffeic and chlorogenic acids to the early diet could also protect against ES-induced cognitive deficits. We induced ES via the limited nesting and bedding paradigm in mice from postnatal(P) day 2-9. On P2, mice received a diet to which 0.02% chlorogenic acid (5-O-caffeoylquinic acid) + 0.02% caffeic acid (3',4'-dihydroxycinnamic acid) were added, or a control diet up until P42. At 4 months of age, all mice were subjected to a behavioral test battery and their brains were stained for markers for microglia and neurogenesis. We found that coffee polyphenols supplemented early in life protected against ES-induced cognitive deficits, potentially this is mediated by the survival of neurons or microglia, but possibly other mechanisms not studied here are mediating the effects. This study provides additional support for the potential of early nutritional interventions and highlights polyphenols as nutrients that can protect against cognitive decline, in particular for vulnerable populations exposed to ES.

Assessing the contribution of the chemical exposome to neurodegenerative disease.

Over the past few decades, numerous environmental chemicals from solvents to pesticides have been suggested to be involved in the development and progression of neurodegenerative diseases. Most of the evidence has accumulated from occupational or cohort studies in humans or laboratory research in animal models, with a range of chemicals being implicated. What has been missing is a systematic approach analogous to genome-wide association studies, which have identified dozens of genes involved in Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. Fortunately, it is now possible to study hundreds to thousands of chemical features under the exposome framework. This Perspective explores how advances in mass spectrometry make it possible to generate exposomic data to complement genomic data and thereby better understand neurodegenerative diseases.

Association of a MIND Diet with Brain Structure and Dementia in a French Population.

BACKGROUND: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines higher consumption of vegetables, berries, nuts, whole grains, olive oil, fish, beans and poultry, with lower consumption of meat, sugars and saturated fats, is a promising strategy to prevent dementia. However, evidence in populations with non-US food culture, especially from Europe, is limited. OBJECTIVES: To evaluate the association of a French-adapted MIND diet score with gray matter volumes, white matter microstructure and incident dementia. DESIGN AND SETTING: This longitudinal study included participants from the population-based Three-City Bordeaux cohort (≥65 years), with a follow-up from June 2001 to February 2018. PARTICIPANTS: Dementia-free participants at dietary assessment, in 2001-2002, who underwent systematic detection of incident dementia (over up to 7 visits). A subset of the cohort was included in an ancillary MRI study in 2010-2011. MEASUREMENTS: A French-adapted MIND diet score (range, 0-15) was computed from a 148-item Food Frequency Questionnaire and a 24-hour recall administered at home. Incident dementia and its subtypes were adjudicated by an expert committee; and gray matter volumes and white matter microstructure were assessed by 3D-T1 MRI and diffusion-MRI. RESULTS: Among 1,412 participants (mean age, 75.8 [SD, 4.8]; 63% women), followed for a median of 9.7 years (maximum 16.3 years), 356 (25.2%) developed incident dementia. In multivariable-adjusted Cox model, a higher French MIND diet score was associated with lower risks of dementia and AD (hazard ratios for 1-point of score = 0.89 [95% confidence interval, 0.83-0.95] and 0.88 [0.81-0.96], respectively). In Tract-Based Spatial Statistics analysis of 175 participants included in the MRI sub-study, a higher MIND diet score was associated with lower diffusivity values in the splenium of the corpus callosum (P < .05 after Family-Wise Error-correction). In contrast, there was no significant association of the adapted MIND diet score with gray matter volumes in Voxel-Based Morphometry analysis. CONCLUSION: In this cohort of French older adults, higher adherence to the French MIND diet was associated with a lower dementia risk and with preserved white matter microstructure. These results provide further evidence for a role of the MIND diet in the prevention of dementia.