The impact of cranberry polyphenols on the brain and gut microbiome in healthy ageing

Ageing is associated with increasing risk of cognitive decline, and modifiable lifestyle factors including diet have been shown to significantly affect the progression of age-related neurodegeneration. Specific dietary components, particularly polyphenol-rich berries such as cranberries, have been increasingly recognised for their effects on the mechanisms underlying age-related neurodegeneration, including the alteration of the gut microbiome and its functions. However, the impact of cranberries on cognition, brain function and the gut microbiome in healthy older adults remains little explored. A 12-week randomised placebo-controlled trial of freeze-dried cranberry powder was conducted in 60 healthy older adults aged between 50 and 80 years. Cognitive assessment, including memory and executive function, neuroimaging, and blood, stool and urine sample collection were conducted before and after the intervention to assess the impact of daily cranberry consumption on cognition, brain function, and the structure and function of the gut microbiome. Cranberry supplementation significantly improved visual episodic memory, with mechanisms of action underpinned by increased regional perfusion in the right entorhinal cortex, the nucleus accumbens area and the caudate. A beneficial shift in microbial abundances in bacterial families relating to polyphenol degradation was also detected in the cranberry group, which correlated with increased levels of circulating polyphenol metabolites in plasma. Gut bacteria-derived metabolites such as TMAO and hippuric acid were also significantly related to improved episodic memory in the cranberry group, although common polyphenol metabolites did not relate to cognitive performance or brain perfusion. These results indicate that daily cranberry supplementation over a 12-week period improved episodic memory performance and neural functioning, corresponding with a beneficial shift in the composition and function of the gut microbiome. These findings provide a basis for future investigations to determine efficacy of intake of high-polyphenol cranberry in the context slowing the onset of neurodegenerative diseases, such as Alzheimer’s disease

Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

Behavioral variant frontotemporal dementia (bvFTD) has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD). Considering the critical role the striatum has in cognition and behavior, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white-matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. In contrast, AD showed few frontostriatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal–ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms

Accelerated Long Term Forgetting in patients with focal seizures: Incidence rate and contributing factors

Background: Accelerated Long Term Forgetting (ALF) is usually defined as a memory impairment that is seen only at long delays (e.g., after days or weeks) and not at shorter delays (e.g., 30 min) typically used in clinical settings. Research indicates that ALF occurs in some patients with epilepsy, but the incidence rates and underlying causes have not been established. In this study, we considered these issues. Methods: Forty-four patients with a history of focal seizures were tested at 30 min and 7 day delays for material from the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Test. Recently published norms from a matched group of 60 control subjects (Miller et al., 2015 ) were used to determine whether patients demonstrated ALF, impairment at 30 min or intact memory performance. Results: The incidence of ALF in the epilepsy patients (18%) was > 3 times higher than normal on the RAVLT, but no different (7%) from the incidence in normal subjects on the Aggie Figures. A different, but again significantly high, proportion of patients (36%) showed shorter-term memory deficits on at least one task. ALF was found mainly in patients with temporal-lobe epilepsy, but also occurred in one patient with an extratemporal seizure focus. Presence of a hippocampal lesion was the main predicting factor of ALF. Conclusions: Many patients with a focal seizure disorder show memory deficits after longer delays that are not evident on standard assessment. The present study explored the factors associated with this ALF memory profile. These new findings will enhance clinical practice, particularly the management of patients with memory complaints

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study

Background: Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS. Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. Methods: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales. Results: Significantly higher atrophy ratings in the bilateral MOFC in ALS patients versus controls was only observed (p<.05). Patients with higher MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05). Conclusions: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management

Executive and social-cognitive determinants of environmental dependency syndrome in behavioral frontotemporal dementia

Objective: Environmental dependency syndrome (EDS), including utilization (UB) and imitation (IB) behaviors, is often reported in behavioral variant frontotemporal dementia (bvFTD). These behaviors are commonly attributed to executive dysfunction. However, inconsistent associations between EDS and poor executive performance has led to an alternative “social hypothesis,” instead implicating patients’ misinterpretation of the examiner’s intention. We investigated the possible explanatory cognitive mechanisms of EDS in bvFTD by relating UB and IB to performance on tests of executive functioning and theory of mind (ToM). Method: This study analyzed retrospective data of 32 bvFTD patients. Data included scores of UB and IB, various executive measures, and ToM assessment using the faux pas test, from which we extracted a mental attribution score. Results: Of the patients, 15.6% and 40.6% exhibited UB and IB, respectively. We conducted an automatic linear modeling analysis with executive and mental attribution measures as predictor variables, and UB and IB sequentially considered as target variables. ToM mental attribution score, visual abstraction and flexibility measures from the Wisconsin Card Sorting Test, and motor sequence performance significantly (corrected ps < .05) predicted IB. No executive or ToM measures significantly predicted UB. Conclusions: These findings reveal a complex interaction between executive dysfunction and mental attribution deficits influencing the prevalence of EDS in bvFTD. Further investigation is required to improve our understanding of the mechanisms underlying these behaviors

Structural anatomical investigation of long-term memory deficit in behavioural frontotemporal dementia

Although a growing body of work has shown that behavioral variant frontotemporal dementia (bvFTD) could present with severe amnesia in approximately half of cases, memory assessment is currently the clinical standard to distinguish bvFTD from Alzheimer's disease (AD). Thus, the concept of "relatively preserved episodic memory" in bvFTD remains the basis of its clinical distinction from AD and a criterion for bvFTD's diagnosis. This view is supported by the idea that bvFTD is not characterized by genuine amnesia and hippocampal degeneration, by contrast to AD. In this multicenter study, we aimed to investigate the neural correlates of memory performance in bvFTD as assessed by the Free and Cued Selective Reminding Test (FCSRT). Imaging explorations followed a two-step procedure, first relying on a visual rating of atrophy of 35 bvFTD and 34ADpatients' MRI, contrasted with 29 controls; and then using voxel-based morphometry (VBM) in a subset of bvFTD patients. Results showed that 43% of bvFTD patients presented with a genuine amnesia. Data-driven analysis on visual rating data showed that, in bvFTD, memory recall & storage performances were significantly predicted by atrophy in rostral prefrontal and hippocampal/perihippocampal regions, similar to mild AD. VBM results in bvFTD (p(FWE)<0.05) showed similar prefrontal and hippocampal regions in addition to striatal and lateral temporal involvement. Our findingsDistALZ CONICET CONICYT/FONDECYT 1170010 1160940 FONCyT, PICT 2012-0412 2012-1309 CONICYT/FONDAP 15150012 INECO Foundatio

Cut-off scores for mild and moderate dementia on the Addenbrooke's Cognitive Examination-III and the Mini-Addenbrooke's Cognitive Examination compared with the Mini-Mental State Examination

Aims and method We aimed to establish cut-off scores to stage dementia on the Addenbrooke's Cognitive Examination-III (ACE-III) and the Mini-Addenbrooke's Cognitive Examination (M-ACE) compared with scores traditionally used with the Mini-Mental State Examination (MMSE). Our cross-sectional study recruited 80 patients and carers from secondary care services in the UK. Results A score ≤76 on the ACE-III and ≤19 on the M-ACE correlated well with MMSE cut-offs for mild dementia, with a good fit on the receiver operating characteristic analysis for both the ACE-III and M-ACE. The cut-off for moderate dementia had lower sensitivity and specificity. There were low to moderate correlations between the cognitive scales and scales for everyday functioning and behaviour. Clinical implications Our findings allow an objective interpretation of scores on the ACE-III and the M-ACE relative to the MMSE, which may be helpful for clinical services and research trials