Vyara Valkanova

Vascular Risk Factors and Depression in Later Life: A Systematic Review and Meta-Analysis

Reports of the association between cardiovascular risk factors and depression in later life are inconsistent; to establish the nature of their association seems important for prevention and treatment of late-life depression. We searched MEDLINE, EMBASE, and PsycINFO for relevant cohort or case control studies over the last 22 years; 1097 were retrieved; 26 met inclusion criteria. Separate meta-analyses were performed for Risk Factor Composite Scores (RFCS) combining different subsets of risk factors, Framingham Stroke Risk Score, and single factors. We found a positive association (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.27-1.75) between RFCS and late-life depression. There was no association between Framingham Stroke Risk Score (OR: 1.25; 95% CI: .99-1.57), hypertension (OR: 1.14; 95% CI: .94-1.40), or dyslipidemia (OR: 1.08; 95% CI: .91-1.28) and late-life depression. The association with smoking was weak (OR: 1.35; 95% CI: 1.00-1.81), whereas positive associations were found with diabetes (OR: 1.51; 95% CI: 1.30-1.76), cardiovascular disease (OR: 1.76; 95% CI: 1.52-2.04), and stroke (OR: 2.11; 95% CI: 1.61-2.77). Moderate to high heterogeneity was found in the results for RFCS, smoking, hypertension, dyslipidemia, and stroke, whereas publication bias was detected for RFCS and diabetes. We therefore found convincing evidence of a strong relationship between key diseases and depression (cardiovascular disease, diabetes, and stroke) and between composite vascular risk and depression but not between some vascular risk factors (hypertension, smoking, dyslipidemia) and depression. More evidence is needed to be accumulated from large longitudinal epidemiological studies, particularly if complemented by neuroimaging.

Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study

Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function. Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15). Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy). Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were “alcohol dependent” according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data. Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning. Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall. Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.

Mind over matter--what do we know about neuroplasticity in adults?

BACKGROUND An increasing number of studies have examined the effects of training of cognitive and other tasks on brain structure, using magnetic resonance imaging. METHODS Studies combining cognitive and other tasks training with longitudinal imaging designs were reviewed, with a view to identify paradigms potentially applicable to treatment of cognitive impairment. RESULTS We identified 36 studies, employing training as variable as juggling, working memory, meditation, learning abstract information, and aerobic exercise. There were training-related structural changes, increases in gray matter volume, decreases, increases and decreases in different regions, or no change at all. There was increased integrity in white matter following training, but other patterns of results were also reported. CONCLUSIONS Questions still to be answered are: Are changes due to use-dependent effects or are they specific to learning? What are the underlying neural correlates of learning, the temporal dynamics of changes, the relations between structure and function, and the upper limits of improvement? How can gains be maintained? The question whether neuroplasticity will contribute to the treatment of dementia will need to be posed again at that stage.

A systematic review and meta-analysis of cross-sectional studies examining the relationship between mobility and cognition in healthy older adults

Highlights • Twenty-six studies were identified as eligible for this systematic review.• Mobility was positively associated with cognitive measures in healthy older adults.• The cognition-mobility relationship spans across cognitive domains.• Meta-analyses on extracted data revealed significant, albeit small, effect sizes.

Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up.

BACKGROUND Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure. AIMS To examine lifetime blood pressure as a predictor of brain structure in old age. METHOD A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985-2013). In 2012-2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities. RESULTS Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy. CONCLUSIONS Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose-response pattern.

What can gait tell us about dementia? Review of epidemiological and neuropsychological evidence

BACKGROUND Cognitive impairment and gait disorders in people over the age of 65 represent major public health issues because of their high frequency, their link to poor outcomes and high costs. Research has demonstrated that these two geriatric syndromes are closely related. METHODS AND RESULTS We aim to review the evidence supporting the relationship between gait and cognitive impairment, particularly focusing on epidemiological and neuropsychological studies in patients with Mild cognitive impairment, Alzheimers disease and Vascular dementia. The review demonstrates that gait and cognition are closely related, but our knowledge of their interrelationship is limited. Emerging evidence shows that gait analysis has the potential to contribute to diagnosis and prognosis of cognitive impairment. CONCLUSIONS An integrated approach for evaluating these major geriatric syndromes, based on their close relationship, will not only increase our understanding of cognitive-motor interactions, but most importantly may be used to aid early diagnosis, prognosis and the development of new interventions.

Neuroimaging in dementia.

Over the last few years, advances in neuroimaging have generated biomarkers, which increase diagnostic certainty, provide valuable information about prognosis, and suggest a particular pathology underlying the clinical dementia syndrome. We aim to review the evidence for use of already established imaging modalities, along with selected techniques that have a great potential to guide clinical decisions in the future. We discuss structural, functional and molecular imaging, focusing on the most common dementias: Alzheimers disease, fronto-temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we stress the importance of conducting research using representative cohorts and in a naturalistic set up, in order to build a strong evidence base for translating imaging methods for a National Health Service. If we assess a broad range of patients referred to memory clinic with a variety of imaging modalities, we will make a step towards accumulating robust evidence and ultimately closing the gap between the dramatic advances in neurosciences and meaningful clinical applications for the maximum benefit of our patients.

Diagnosing early cognitive decline-When, how and for whom?

Mild cognitive impairment (MCI) is a term used to describe cognitive impairment in one or more cognitive domains that is greater than any expected age-related changes, but not of the magnitude to warrant a diagnosis of dementia. This review considers how early cognitive decline is diagnosed, focusing on the use of neuropsychological tests and neuroimaging, as well as the differential diagnosis. Potential treatments, including secondary prevention, post-diagnostic support and self-help are discussed. Finally, medico-legal matters such as driving, lasting power of attorney and employment are outlined.

Resilience and MRI correlates of cognitive impairment in community-dwelling elders.

Background The contribution of education and intelligence to resilience against age-related cognitive decline is not clear, particularly in the presence of ‘normal for age’ minor brain abnormalities. Method Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes. Results Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) <26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy. Conclusions Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment.

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.Highlights • Gait is thought to have a cognitive component, but the evidence in elderly is mixed.• We studied the association between multiple gait and cognitive measures.• No strong relationship in a cognitively healthy, high functioning sample of elderly.• Nevertheless we find some relationships with spatial, but not temporal gait.• White matter hyperintensities made no independent contribution to gait measures.