Distinct resting-state functional connections associated with episodic and visuospatial memory in older adults.

Episodic and spatial memory are commonly impaired in ageing and Alzheimer's disease. Volumetric and task-based functional magnetic resonance imaging (fMRI) studies suggest a preferential involvement of the medial temporal lobe (MTL), particularly the hippocampus, in episodic and spatial memory processing. The present study examined how these two memory types were related in terms of their associated resting-state functional architecture. 3T multiband resting state fMRI scans from 497 participants (60-82 years old) of the cross-sectional Whitehall II Imaging sub-study were analysed using an unbiased, data-driven network-modelling technique (FSLNets). Factor analysis was performed on the cognitive battery; the Hopkins Verbal Learning test and Rey-Osterreith Complex Figure test factors were used to assess verbal and visuospatial memory respectively. We present a map of the macroscopic functional connectome for the Whitehall II Imaging sub-study, comprising 58 functionally distinct nodes clustered into five major resting-state networks. Within this map we identified distinct functional connections associated with verbal and visuospatial memory. Functional anticorrelation between the hippocampal formation and the frontal pole was significantly associated with better verbal memory in an age-dependent manner. In contrast, hippocampus-motor and parietal-motor functional connections were associated with visuospatial memory independently of age. These relationships were not driven by grey matter volume and were unique to the respective memory domain. Our findings provide new insights into current models of brain-behaviour interactions, and suggest that while both episodic and visuospatial memory engage MTL nodes of the default mode network, the two memory domains differ in terms of the associated functional connections between the MTL and other resting-state brain networks

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

BACKGROUND: There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer's disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging. METHODS: We included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity). FINDINGS: Younger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without. CONCLUSIONS: Resilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms

The influence of diet and metabolism on hippocampus and hypothalamus connectivity across the lifespan

The high prevalence of unhealthy dietary patterns, obesity, and related brain disorders such as dementia emphasise the importance of research that examines the effect of dietary and metabolic factors on brain health. Using magnetic resonance imaging (MRI) to assess brain grey matter functional connectivity (FC) and volumes, this thesis aimed to examine the relationship between measures of diet and metabolism and the brain over the adult lifespan. First, a systematic review was conducted, to examine the relationship between dietary and metabolic health in relation to a wide range of brain MRI markers. The reviewed evidence suggested that lower dietary and metabolic health quality was related to reduced brain volume and connectivity, especially in the default mode network and the frontal and temporal lobes, although there were contrasting trends for each of these associations. To address the gaps identified by the review, we examined the association between dietary and metabolic health in relation to the hippocampus and hypothalamus FC and volumes in the cross-sectional Human Connectome Project cohort of 400 younger adults and in the longitudinal Whitehall II cohort of 775 midlife-older aged adults. The Whitehall cohort had longitudinal measures of diet/metabolic markers collected every 5 years throughout their midlife (40-70 years old). First, we note that different dietary and metabolic markers have unique patterns of longitudinal trajectories from mid-to-old-age. Our findings supported the hypothesis that better dietary and metabolic health is associated with volumetric and FC differences of the hippocampus and the hypothalamus both in younger and older cohorts. Specifically, dietary and metabolic health was linked to (1) hippocampal FC with the frontal lobe, precentral gyrus, and occipital lobe and (2) hypothalamic FC with the brainstem and the basal forebrain. These findings contribute to a growing understanding of the brain networks associated with dietary and metabolic health. The thesis provides insights into when in life dietary and metabolic health measures are related to brain health. Our findings indicated that in order to promote brain health in older age, some metabolic factors may be better targeted in midlife (e.g., cholesterol, diet, abdominal fat), while other factors should be targeted as early as possible (blood pressure, body composition/BMI). This may have implications for preventative lifestyle interventions to reduce the risk of developing dementia and to maintain overall brain health