End-to-end volumetric segmentation of white matter hyperintensities using deep learning.

BACKGROUND AND OBJECTIVES: Reliable detection of white matter hyperintensities (WMH) is crucial for studying the impact of diffuse white-matter pathology on brain health and monitoring changes in WMH load over time. However, manual annotation of 3D high-dimensional neuroimages is laborious and can be prone to biases and errors in the annotation procedure. In this study, we evaluate the performance of deep learning (DL) segmentation tools and propose a novel volumetric segmentation model incorporating self-attention via a transformer-based architecture. Ultimately, we aim to evaluate diverse factors that influence WMH segmentation, aiming for a comprehensive analysis of the state-of-the-art algorithms in a broader context. METHODS: We trained state-of-the-art DL algorithms, and incorporated advanced attention mechanisms, using structural fluid-attenuated inversion recovery (FLAIR) image acquisitions. The anatomical MRI data utilized for model training was obtained from healthy individuals aged 62-70 years in the Live active Successful Aging (LISA) project. Given the potential sparsity of lesion volume among healthy aging individuals, we explored the impact of incorporating a weighted loss function and ensemble models. To assess the generalizability of the studied DL models, we applied the trained algorithm to an independent subset of data sourced from the MICCAI WMH challenge (MWSC). Notably, this subset had vastly different acquisition parameters compared to the LISA dataset used for training. RESULTS: Consistently, DL approaches exhibited commendable segmentation performance, achieving the level of inter-rater agreement comparable to expert performance, ensuring superior quality segmentation outcomes. On the out of sample dataset, the ensemble models exhibited the most outstanding performance. CONCLUSIONS: DL methods generally surpassed conventional approaches in our study. While all DL methods performed comparably, incorporating attention mechanisms could prove advantageous in future applications with a wider availability of training data. As expected, our experiments indicate that the use of ensemble-based models enables the superior generalization in out-of-distribution settings. We believe that introducing DL methods in the WHM annotation workflow in heathy aging cohorts is promising, not only for reducing the annotation time required, but also for eventually improving accuracy and robustness via incorporating the automatic segmentations in the evaluation procedure.

Effects of acute physical activity on brain metabolites as measured by magnetic resonance spectroscopy (1H-MRS) in humans: A systematic review.

Physical activity (PA) promotes brain health in a variety of domains including cognition, mood, and neuroplasticity. At the neurochemical level, the mechanisms underlying these effects in the brain are not fully understood. With proton Magnetic Resonance Spectroscopy (1H-MRS), it is possible to non-invasively quantify metabolite concentrations, enabling studies to obtain measures of exercise-induced neurochemical changes. This systematic review aimed to examine the existing literature on acute effects of PA on brain metabolites as measured by 1H-MRS. Four databases (Cochrane Central Register of Controlled Trials, PubMed, Embase, and PsycINFO) were searched, identifying 2965 studies, of which 9 met the inclusion criteria. Across studies, Gamma-AminoButyric Acid (GABA) and lactate tended to increase after exercise, while no significant changes in choline were reported. For glutamine/glutamate (Glx), studies were inconclusive. Conclusions were limited by the lack of consensus on 1H-MRS data processing and exercise protocols. To reduce inter-study differences, future studies are recommended to (1): apply a standardized exercise index (2), consider the onset time of MRS scans, and (3) follow standardized MRS quantification methods.

Characterising the covariance pattern between lifestyle factors and structural brain measures: a multivariable replication study of two independent ageing cohorts.

Modifiable lifestyle factors have been shown to promote healthy brain ageing. However, studies have typically focused on a single factor at a time. Given that lifestyle factors do not occur in isolation, multivariable analyses provide a more realistic model of the lifestyle-brain relationship. Here, canonical correlation analyses (CCA) examined the relationship between nine lifestyle factors and seven MRI-derived indices of brain structure. The resulting covariance pattern was further explored with Bayesian regressions. CCA analyses were first conducted on a Danish cohort of older adults (n = 251) and then replicated in a British cohort (n = 668). In both cohorts, the latent factors of lifestyle and brain structure were positively correlated (UK: r = .37, p < 0.001; Denmark: r = .27, p < 0.001). In the cross-validation study, the correlation between lifestyle-brain latent factors was r = .10, p = 0.008. However, the pattern of associations differed between datasets. These findings suggest that baseline characterisation and tailoring towards the study sample may be beneficial for achieving targeted lifestyle interventions.

No moderating influence of education on the association between changes in hippocampus volume and memory performance in aging.

Contemporary accounts of factors that may modify the risk for age-related neurocognitive disorders highlight education and its contribution to a cognitive reserve. By this view, individuals with higher educational attainment should show weaker associations between changes in brain and cognition than individuals with lower educational attainment. We tested this prediction in longitudinal data on hippocampus volume and episodic memory from 708 middle-aged and older individuals using local structural equation modeling. This technique does not require categorization of years of education and does not constrain the shape of relationships, thereby maximizing the chances of revealing an effect of education on the hippocampus-memory association. The results showed that the data were plausible under the assumption that there was no influence of education on the association between change in episodic memory and change in hippocampus volume. Restricting the sample to individuals with elevated genetic risk for dementia (APOE ε4 carriers) did not change these results. We conclude that the influence of education on changes in episodic memory and hippocampus volume is inconsistent with predictions by the cognitive reserve theory.

Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan: A pooled analysis in the European Lifebrain consortium.

BACKGROUND: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. METHODS: We included 3838 participants aged 18-90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. RESULTS: High alcohol use was associated with lower hippocampal volume (r = -0.10, p = 0.021), and overweight/obesity with lower total GMV (r = -0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = -0.08, p = 0.001), but not hippocampal volume (r = -0.01, p = 0.625). CONCLUSIONS: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.

Is it all in the baseline? Trajectories of chair stand performance over 4 years and their association with grey matter structure in older adults.

Understanding individual variability in response to physical activity is key to developing more effective and personalised interventions for healthy ageing. Here, we aimed to unpack individual differences by using longitudinal data from a randomised-controlled trial of a 12-month muscle strengthening intervention in older adults. Physical function of the lower extremities was collected from 247 participants (66.3 ± 2.5 years) at four time-points. At baseline and at year 4, participants underwent 3 T MRI brain scans. K-means longitudinal clustering was used to identify patterns of change in chair stand performance over 4 years, and voxel-based morphometry was applied to map structural grey matter volume at baseline and year 4. Results identified three groups showing trajectories of poor (33.6%), mid (40.1%), and high (26.3%) performance. Baseline physical function, sex, and depressive symptoms significantly differed between trajectory groups. High performers showed greater grey matter volume in the motor cerebellum compared to the poor performers. After accounting for baseline chair stand performance, participants were re-assigned to one of four trajectory-based groups: moderate improvers (38.9%), maintainers (38.5%), improvers (13%), and decliners (9.7%). Clusters of significant grey matter differences were observed between improvers and decliners in the right supplementary motor area. Trajectory-based group assignments were unrelated to the intervention arms of the study. In conclusion, patterns of change in chair stand performance were associated with greater grey matter volumes in cerebellar and cortical motor regions. Our findings emphasise that how you start matters, as baseline chair stand performance was associated with cerebellar volume 4 years later.

Examining the Impact of Socioeconomic Position Across the Life Course on Cognitive Function and Brain Structure in Healthy Aging.

This study explores the relationship of life-course intergenerational social mobility with cognitive function and brain structure in older adults using Diagonal Reference Models. Data from the Irish Longitudinal Study on Ageing, a population-based cohort of adults aged 50 years and older (N = 4 620 participants; mean age: 66.1; standard deviation: 9.1; 55% female) was used for analysis. Brain magnetic resonance imaging data were available for 464 participants. Social mobility was characterized as the difference between childhood socioeconomic position (SEP; ie, father's occupation) and adulthood SEP (ie, own occupation). The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), cortical thickness, and total gray matter volume (GMV) served as global cognitive and brain measures. Exploratory analyses included the volumes of the ventromedial prefrontal cortex (vmPFC), anterior cingulate (AC), hippocampus, and amygdala. A social gradient in cognitive function was observed among the intergenerationally stable; brain structure was not as clearly socially patterned. Adulthood SEP was significantly associated with MoCA (weight = 0.76; p < .001), MMSE (weight = 0.91; p < .001), GMV (weight = 0.77; p = .002), and AC volume (weight = 0.76; p < .001), whereas childhood SEP was associated with vmPFC volume (weight = 1.00; p = .003). There was no independent association of social mobility with any of the outcomes. Together our results suggest that both childhood and adulthood SEP are important in shaping later-life brain health, but that adulthood SEP predominates in terms of its influence. This is potentially an important insight as it suggests that brain health may be modifiable if socioeconomic circumstances change.

Individual differences in brain aging: heterogeneity in cortico-hippocampal but not caudate atrophy rates.

It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.

Hippocampal maintenance after a 12-month physical activity intervention in older adults: The REACT MRI study.

BACKGROUND: Physical activity interventions have had varying results on modifying hippocampal volume. METHODS: The Retirement in Action (REACT) study conducted a randomised-controlled trial of a 12-month physical activity and behaviour maintenance intervention in older adults at risk of mobility impairments. The physical activity sessions were delivered twice weekly for the first twelve weeks, and then reduced to once weekly, to groups of 15 participants. Activities included cardiovascular, strength, balance and flexibility exercises. A sub-sample of participants in the physical activity (N = 54) and control arms (N = 48) underwent a 3 T MRI brain scan and cognitive assessments at baseline, 6- and 12-months (mean age = 76.6 years, 6.8 SD). It was hypothesised that the intervention would lead to a reduced rate of decline in hippocampal volume. Group differences in changes in cognition were also examined. RESULTS: As hypothesised, we found a maintenance in left hippocampal volume in the intervention arm, in comparison with the control arm after 12 months (p = 0.027). In a secondary analysis, this effect was attenuated after including age, sex and education level as covariates (p = 0.057). There was no significant between-group difference in the right hippocampus (p = 0.405). Contrary to our hypothesis, we did not find a beneficial effect of the intervention on cognitive outcomes. CONCLUSIONS: Our findings suggest that a community-based physical activity intervention can significantly ward-off hippocampal atrophy in older adults. While the lack of effects on cognition may limit the interpretability of our results, our findings of hippocampal maintenance are promising given the potential clinical relevance of protecting the hippocampus from age-related decline.

Effect of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: the REACT (Retirement in Action) randomised controlled trial.

BACKGROUND: Mobility limitations in old age can greatly reduce quality of life, generate substantial health and social care costs, and increase mortality. Through the Retirement in Action (REACT) trial, we aimed to establish whether a community-based active ageing intervention could prevent decline in lower limb physical functioning in older adults already at increased risk of mobility limitation. METHODS: In this pragmatic, multicentre, two-arm, single-blind, parallel-group, randomised, controlled trial, we recruited older adults (aged 65 years or older and who are not in full-time employment) with reduced lower limb physical functioning (Short Physical Performance Battery [SPPB] score 4-9) from 35 primary care practices across three sites (Bristol and Bath; Birmingham; and Devon) in England. Participants were randomly assigned to receive brief advice (three healthy ageing education sessions) or a 12-month, group-based, multimodal physical activity (64 1-h exercise sessions) and behavioural maintenance (21 45-min sessions) programme delivered by charity and community or leisure centre staff in local communities. Randomisation was stratified by site and adopted a minimisation approach to balance groups by age, sex, and SPPB score, using a centralised, online, randomisation algorithm. Researchers involved in data collection and analysis were masked but participants were not because of the nature of the intervention. The primary outcome was change in SPPB score at 24 months, analysed by intention to treat. This trial is registered with ISRCTN, ISRCTN45627165. FINDINGS: Between June 20, 2016, and Oct 30, 2017, 777 participants (mean age 77·6 [SD 6·8] years; 66% female; mean SPPB score 7·37 [1·56]) were randomly assigned to the intervention (n=410) and control (n=367) groups. Primary outcome data at 24 months were provided by 628 (81%) participants (294 in the control group and 334 in the intervention group). At the 24-month follow-up, the SPPB score (adjusted for baseline SPPB score, age, sex, study site, and exercise group) was significantly greater in the intervention group (mean 8·08 [SD 2·87]) than in the control group (mean 7·59 [2·61]), with an adjusted mean difference of 0·49 (95% CI 0·06-0·92; p=0·014), which is just below our predefined clinically meaningful difference of 0·50. One adverse event was related to the intervention; the most common unrelated adverse events were heart conditions, strokes, and falls. INTERPRETATION: For older adults at risk of mobility limitations, the REACT intervention showed that a 12-month physical activity and behavioural maintenance programme could help prevent decline in physical function over a 24-month period. FUNDING: National Institute for Health Research Public Health Research Programme (13/164/51).

Physical Function, An Adjunct to Brain Health Score for Phenotyping Cognitive Function Trajectories in Older Age: Findings From The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Evidence is limited regarding the cumulative effect of risk factors on cognitive decline and the added value of physical function for cognitive function trajectory stratification. We operationalize 13 modifiable dementia risk factors in a scoring system and investigate the relationship between this brain health score, combined with simple measures of physical function, and risk of cognitive decline. METHODS: Population-based cohort study of persons aged 50 and older from the Irish Longitudinal Study on Ageing without a history of dementia at baseline who underwent repeated neuropsychological tests (8.08 ± 0.3-year follow-up) were included in the analyses. Exposures were the number of brain health metrics (defined by the Lancet Commission on Dementia Prevention, Intervention, and Care report) at recommended optimal levels. Physical function exposures included Timed Up and Go, dual-task walking speed, and grip strength. Each health metric and physical function measure at the recommended level was assigned a value of 1 and combined to generate brain health scores. Relationship with group-based trajectories of global cognitive function (multidomains composite score), estimated using K-means for longitudinal data, was assessed via ordinal logistic regressions. RESULTS: Among 2 327 participants (mean age, 61 years; 54% women), each additional optimal metric on the brain health score (odds 0.67 [0.62, 0.73]) was associated with reduced odds of cognitive decline. Adding Timed Up and Go (odds 0.71 [0.59, 0.84]) and dual-task walking speed (odds 0.74 [0.63, 0.89]) further improved model fit (ΔAIC = 14.8). CONCLUSION: These findings support the promotion and maintenance of physical function in addition to brain health strategies to reduce the risk of cognitive decline.

Sex differences in the incidence and prevalence of young-onset Alzheimer's disease: A meta-analysis.

OBJECTIVES: The lifetime incidence of Alzheimer's disease is higher in women than in men, but it remains unclear if similar sex differences exist in young-onset Alzheimer's disease (YOAD). This systematic review test the hypothesis that women have a higher prevalence and incidence of YOAD than men. METHODS: We searched Pubmed and Embase (inception to 11 June 2020) for original publications of population-based observational studies with data on the prevalence and/or incidence of YOAD, defined as a medical diagnosis of Alzheimer's disease before the age of 65 years. Data on cross-sectional and/or prospective numbers, percentages, incidences, and incidence rates (in person-years) were derived from included studies. Quality assessment was done using the Nottingham Ottawa Scale. Meta-analyses were done to test the hypothesis that women have a higher prevalence and incidence of YOAD than men. RESULTS: After screening of 3252 titles, 12 articles were included. The pooled prevalence was 0.4% (confidence interval [CI] = 0.1-2.1) in women and 0.2% (CI = 0-1.2) in men (six studies, relative risk [RR] = 1.54, CI = 0.69-3.44, I2  = 38%). The pooled incidence was 0.02% (CI = 0.01-0.08) in women and 0.01% (CI = 0-0.05) in men (five studies, RR = 1.50, CI = 0.91-2.48, I2  = 0%). The incidence rates per 100,000 person-years ranged from 0 to 132 in women and from 0 to 42 in men. CONCLUSIONS: Given the low prevalence and wide CIs, no firm conclusions can be drawn. Large-scale studies are required to verify that women are more likely than men to develop YOAD.

Right-left asymmetry in corticospinal tract microstructure and dexterity are uncoupled in late adulthood.

Ageing leads to a decline in white matter microstructure and dexterous function of the hand. In adolescents, it has previously been shown that the degree of right-left asymmetry in the corticospinal tract (CST) is linearly related with right-left asymmetry in dexterity. Here, we tested whether this association is also expressed in older adults. Participants completed a simple circle drawing task with their right and left hand as a measure of dexterity and underwent whole-brain diffusion weighted imaging at 3 Tesla (n = 199; aged 60-72 years). Fractional anisotropy and mean diffusivity of right and left CST were extracted from a manually defined region-of-interest. Linear regression analyses were computed to replicate the analyses in adolescents. Frequentist analyses were complemented with a Bayesian analytical framework. Outcome measures were compared with those previously reported in adolescents (aged 11-16 years). Asymmetries in white matter microstructure of the CST were evident and comparable to the degree of lateralisation observed in adolescence. Similarly, asymmetries in dexterity were evident, but to a lesser degree than in adolescents. Unlike in adolescents, we found no evidence of a linear relationship between asymmetries in CST microstructure and dexterity. Complementary Bayesian regression analysis provided moderate evidence in favour of the null hypothesis, pointing towards a lack of association between the structural and functional measures of right-left asymmetry. Our findings are compatible with the notion that, by late adulthood, a diverging impact of age on white matter structure and dexterous hand function dilutes the structure-function relationship between CST microstructure and manual proficiency that has been reported in adolescents.

Defining brain health: A concept analysis.

OBJECTIVES: Brain health is an important focus for coming decades due to population ageing. Although the term 'brain health' is increasingly used in lay and professional settings, a clear definition of the term is lacking. We conducted an analysis of the concept of brain health to inform policy, practice, and research. METHODS: We applied a hybrid concept analysis method involving three stages: (1) a review of the extant literature for definitions of brain health; (2) field work, involving an international survey of 'brain health' researchers and practitioners; and (3) a final analysis, integrating the findings into a working definition and model. RESULTS: Our review of the literature identified 13 articles defining brain health, six of which proposed their own definition. Our survey revealed that the term 'brain health' was used in diverse ways based on different theoretical frameworks. From the review and survey, we extracted attributes, antecedents, and consequences of brain health. These were synthesized into a definition of brain health as a life-long, multidimensional, dynamic state consisting of cognitive, emotional and motor domains underpinned by physiological processes and can be objectively measured and subjectively experienced. It is influenced by eco-biopsychosocial determinants. CONCLUSION: This working definition of brain health is a foundation for developing policy, practice, research and advocacy. The definition needs to be operationalised through further development of empirical referents, including cross-cultural understanding, adaptation and validation.

Is Fall Risk Systematically Evaluated in Memory Clinics? A National Survey of Practice in France.

BACKGROUND: Falls are a major health problem in older persons but are still under-diagnosed and challenging to prevent. Current guidelines do not target high-risk populations, especially people living with dementia. In France, people with neurocognitive disorders are mainly referred to memory clinics (MCs). OBJECTIVE: We aimed to survey the routine practice of physicians working in MCs regarding fall risk assessment. METHODS: We conducted a cross-sectional survey in France from January to May 2019 among physicians working in MCs, through an anonymous online questionnaire: twenty-seven questions about the physician's background and their practice of fall risk assessment, especially use of clinical and paraclinical tools. We compared the results according to the age and the specialty of the physician. RESULTS: We obtained 171 responses with a majority of women (60%) and geriatricians (78%). All age classes and all French regions were represented. Most of respondents (98.8%) stated that they address gait and/or falls in outpatient clinic and 95.9%in day hospitals. When asked about how they assess fall risk, fall history (83%) and gait examination (68.4%) were the most widely used, while orthostatic hypotension (24%) and clinical standardized tests (25.7%) were less common. Among standardized tests, One-leg Balance, Timed Up and Go Test, and gait speed measurements were the most used. Geriatricians had more complete fall risk assessment than neurologists (e.g., 56%versus 13%for use of standardized tests, p < 0.0001). CONCLUSION: Almost all physicians addressed the question of fall in MC, but practices are widely heterogeneous. Further investigations are needed to standardize fall risk assessment in MCs.

Association of trajectories of depressive symptoms with vascular risk, cognitive function and adverse brain outcomes: The Whitehall II MRI sub-study.

BACKGROUND: Trajectories of depressive symptoms over the lifespan vary between people, but it is unclear whether these differences exhibit distinct characteristics in brain structure and function. METHODS: In order to compare indices of white matter microstructure and cognitive characteristics of groups with different trajectories of depressive symptoms, we examined 774 participants of the Whitehall II Imaging Sub-study, who had completed the depressive subscale of the General Health Questionnaire up to nine times over 25 years. Twenty-seven years after the first examination, participants underwent magnetic resonance imaging to characterize white matter hyperintensities (WMH) and microstructure and completed neuropsychological tests to assess cognition. Twenty-nine years after the first examination, participants completed a further cognitive screening test. OUTCOMES: Using K-means cluster modelling, we identified five trajectory groups of depressive symptoms: consistently low scorers ("low"; n = 505, 62·5%), a subgroup with an early peak in depression scores ("early"; n = 123, 15·9%), intermediate scorers ("middle"; n = 89, 11·5%), a late symptom subgroup with an increase in symptoms towards the end of the follow-up period ("late"; n = 29, 3·7%), and consistently high scorers ("high"; n = 28, 3·6%). The late, but not the consistently high scorers, showed higher mean diffusivity, larger volumes of WMH and impaired executive function. In addition, the late subgroup had higher Framingham Stroke Risk scores throughout the follow-up period, indicating a higher load of vascular risk factors. INTERPRETATION: Our findings suggest that tracking depressive symptoms in the community over time may be a useful tool to identify phenotypes that show different etiologies and cognitive and brain outcomes.

The effects of an aerobic training intervention on cognition, grey matter volumes and white matter microstructure.

While there is strong evidence from observational studies that physical activity is associated with reduced risk of cognitive decline and dementia, the extent to which aerobic training interventions impact on cognitive health and brain structure remains subject to debate. In a pilot study of 46 healthy older adults (66.6 years ± 5.2 years, 63% female), we compared the effects of a twelve-week aerobic training programme to a waitlist control condition on cardiorespiratory fitness, cognition and magnetic resonance imaging (MRI) outcomes. Cardiorespiratory fitness was assessed by VO2 max testing. Cognitive assessments spanned executive function, memory and processing speed. Structural MRI analysis included examination of hippocampal volume, and voxel-wise assessment of grey matter volumes using voxel-based morphometry. Diffusion tensor imaging analysis of fractional anisotropy, axial diffusivity and radial diffusivity was performed using tract-based spatial statistics. While the intervention successfully increased cardiorespiratory fitness, there was no evidence that the aerobic training programme led to changes in cognitive functioning or measures of brain structure in older adults. Interventions that are longer lasting, multi-factorial, or targeted at specific high-risk populations, may yield more encouraging results.

Alcohol consumption is associated with reduced creatine levels in the hippocampus of older adults.

Besides its well established susceptibility to ageing, the hippocampus has also been shown to be affected by alcohol consumption. Proton spectroscopy (1H-MRS) of the hippocampus, particularly at high-field 7T MRI, may further our understanding of these associations. Here, we aimed to examine how hippocampal metabolites varied with age and alcohol consumption. Hippocampal metabolite spectra were acquired in 37 older adults using 7T 1H-MRS, from which we determined the absolute concentration of N-acetylaspartate (NAA), creatine, choline, myo-inositol, glutamate and glutamine. Thirty participants (mean age = 70.4 ± 4.7 years) also had self-reported data on weekly alcohol consumption. Total choline inversely correlated with age, although this did not survive multiple comparisons correction. Crucially, adults with a higher weekly alcohol consumption had significantly lower levels of creatine, suggesting a deficit in their hippocampal metabolism. These findings add to an increasing body of evidence linking alcohol to hippocampal function.

Association between gait and cognition in an elderly population based sample.

BACKGROUND: Gait is thought to have a cognitive component, but the current evidence in healthy elderly is mixed. We studied the association between multiple gait and cognitive measures in a cohort of older people. METHODS: One hundred and seventy-eight cognitively healthy participants from the Whitehall II Imaging Sub-study had a detailed clinical and neuropsychological assessment, as well as an MRI scan. Spatiotemporal and variability gait measures were derived from two 10 m walks at self-selected speed. We did a linear regression analysis, entering potential confounders with backwards elimination of variables with p ≥ 0.1. The remaining variables were then entered into a second regression before doing a stepwise analysis of cognitive measures, entering variables with p < 0.05 and removing those with p ≥ 0.1. RESULTS: Amongst absolute gait measures, only greater stride length was associated with better performance on the Trail Making Test A (p = 0.023) and the Boston Naming Test (p = 0.042). The stride time variability was associated with performance on the Trail Making Test A (p = 0.031). Age was associated with poorer walking speed (p = 0.014) and stride time (p = 0.011), female sex with shorter stride time (p = 0.000) and shorter double stance (p = 0.005). Length of full-time education was associated with faster walking speed (p = 0.012) and shorter stride time (p = 0.045), and a history of muscular-skeletal disease with slower walking speed (p = 0.01) and shorter stride length (p = 0.015). Interestingly, volume of white matter hyperintensities (WMH) on FLAIR MRI images did not contribute independently to any of the gait measures (p > 0.05). CONCLUSIONS: No strong relationship between gait and non-motor cognition was observed in a cognitively healthy, high functioning sample of elderly. Nevertheless, we found some relationships with spatial, but not temporal gait which warrant further investigation. WMH made no independent contributionto gait.