•Lower hippocampal activity predicted greater subjective cognitive decline (SCD)•Amyloid and actual memory decline are both predictors of SCD•Hippocampal activity predicted SCD independently of ...amyloid and actual decline•SCD in old adults appear to reflect their surprising insights into neural deficits.
We evaluated whether self-reports of worse cognition in older adults with normal cognitive function reflected actual memory decline, amyloid pathology, and subtle vulnerabilities in hippocampal function. We measured subjective cognitive decline (SCD) in 156 older participants from the Dallas Lifespan Brain Study. Functional hippocampal activation during encoding, measured with fMRI, and longitudinal memory change that was measured in the four years preceding the SCD measures were used to predict the magnitude of SCD. A subsample (N=105) also underwent 18F-Florbetapir PET imaging that measured amyloid burden. Results showed that increased SCD were associated with greater prior memory decline and amyloid deposition. Importantly, decreased hippocampal activation during encoding was a significant predictor of SCD, particularly in young-old adults below 69 years old, above and beyond prior memory change and amyloid deposition. These results indicate that multiple measures of neural and cognitive dysfunction are simultaneously associated with SCD. Moreover, SCD in younger seniors appears to reflect deficient hippocampal activity that increases their reports of poorer memory, independent of amyloid. This manuscript is part of the Special Issue entitled “Cognitive Neuroscience of Healthy and Pathological Aging” edited by Drs. M. N. Rajah, S. Belleville, and R. Cabeza. This article is part of the Virtual Special Issue titled COGNITIVE NEU-ROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect at https://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.
Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some ...older adults show little decline in cognitive ability compared with young adults and are thus termed 'optimally ageing'. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular - compensation, maintenance and reserve - have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.
The challenges associated with the ageing population are important and continuous growth across the world, especially in Europe, the continent with the oldest population. The fundamental objective of ...active ageing interventions is to optimise opportunities for health, participation and security so as to increase the quality of life of the population with ageing. The Active Ageing Index is a flexible comparative analysis tool that has the mission to help promote and implement active ageing. Thus, the purpose of this paper is to analyse the phenomenon of active ageing from the perspective of the active ageing index in the European area. The methodology used consisted of document analysis, study for several countries in the European space such as: Italy, Germany, Poland, Spain, Romania, analysis and comparison of statistic data. The results obtained show that the role of this active ageing index is to capture the various facets of active ageing, measuring the contribution of older people (women and men) to economic and social life and to the extent to which the environment in which they live stimulates them in this regard to provide more active participation in employment, social life and to lead independent lives.
Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, ...which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.
The structure and integrity of the ageing brain is interchangeably linked to physical health, and cardiometabolic risk factors (CMRs) are associated with dementia and other brain disorders. In this ...mixed cross‐sectional and longitudinal study (interval mean = 19.7 months), including 790 healthy individuals (mean age = 46.7 years, 53% women), we investigated CMRs and health indicators including anthropometric measures, lifestyle factors, and blood biomarkers in relation to brain structure using MRI‐based morphometry and diffusion tensor imaging (DTI). We performed tissue specific brain age prediction using machine learning and performed Bayesian multilevel modeling to assess changes in each CMR over time, their respective association with brain age gap (BAG), and their interaction effects with time and age on the tissue‐specific BAGs. The results showed credible associations between DTI‐based BAG and blood levels of phosphate and mean cell volume (MCV), and between T1‐based BAG and systolic blood pressure, smoking, pulse, and C‐reactive protein (CRP), indicating older‐appearing brains in people with higher cardiometabolic risk (smoking, higher blood pressure and pulse, low‐grade inflammation). Longitudinal evidence supported interactions between both BAGs and waist‐to‐hip ratio (WHR), and between DTI‐based BAG and systolic blood pressure and smoking, indicating accelerated ageing in people with higher cardiometabolic risk (smoking, higher blood pressure, and WHR). The results demonstrate that cardiometabolic risk factors are associated with brain ageing. While randomized controlled trials are needed to establish causality, our results indicate that public health initiatives and treatment strategies targeting modifiable cardiometabolic risk factors may also improve risk trajectories and delay brain ageing.
The structure and integrity of the ageing brain is interchangeably linked to physical health, and cardiometabolic risk factors (CMRs). We investigated CMRs and health indicators including anthropometric measures, lifestyle factors, and blood biomarkers in relation to brain structure using MRI‐based morphometry and diffusion tensor imaging (DTI). Tissue‐specific brain age prediction using machine learning revealed older‐appearing brains and accelerated ageing in people with higher cardiometabolic risk.
It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells ...that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.
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