Ageing and the brain.
TL;DR: Protective factors that reduce cardiovascular risk, namely regular exercise, a healthy diet, and low to moderate alcohol intake, seem to aid the ageing brain as does increased cognitive effort in the form of education or occupational attainment.
Abstract: Ageing causes changes to the brain size, vasculature, and cognition. The brain shrinks with increasing age and there are changes at all levels from molecules to morphology. Incidence of stroke, white matter lesions, and dementia also rise with age, as does level of memory impairment and there are changes in levels of neurotransmitters and hormones. Protective factors that reduce cardiovascular risk, namely regular exercise, a healthy diet, and low to moderate alcohol intake, seem to aid the ageing brain as does increased cognitive effort in the form of education or occupational attainment. A healthy life both physically and mentally may be the best defence against the changes of an ageing brain. Additional measures to prevent cardiovascular disease may also be important.
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TL;DR: The challenge now is to understand the senescence response well enough to harness its benefits while suppressing its drawbacks.
Abstract: Cellular senescence is an important mechanism for preventing the proliferation of potential cancer cells. Recently, however, it has become apparent that this process entails more than a simple cessation of cell growth. In addition to suppressing tumorigenesis, cellular senescence might also promote tissue repair and fuel inflammation associated with aging and cancer progression. Thus, cellular senescence might participate in four complex biological processes (tumor suppression, tumor promotion, aging, and tissue repair), some of which have apparently opposing effects. The challenge now is to understand the senescence response well enough to harness its benefits while suppressing its drawbacks.
1,723 citations
TL;DR: Age predictions can be accurately generated on raw T1‐MRI data, substantially reducing computation time for novel data, bringing the process closer to giving real‐time information on brain health in clinical settings.
610 citations
TL;DR: It will be difficult to understand AD without understanding why it preferably affects older brains, and that a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology is needed.
581 citations
Cites background from "Ageing and the brain."
...Dendritic spine plasticity in the prefrontal cortex is reduced in aged rodents (Bloss et al., 2011), and spine density is likely reduced in aging (Jacobs et al., 1997; Esiri, 2007; Freeman et al., 2008; Benavides-Piccione et al., 2013) (see Fig....
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..., 2011), and spine density is likely reduced in aging (Jacobs et al., 1997; Esiri, 2007; Freeman et al., 2008; Benavides-Piccione et al., 2013) (see Fig....
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TL;DR: Multivariate analyses indicate that the frontal gray matter was most strongly associated with age, while occipital gray and white matter were least associated.
523 citations
TL;DR: Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy.
444 citations
Cites result from "Ageing and the brain."
...Thus, the current study supports the longstanding “last in, first out” hypothesis otherwise known as the phylogenetic/ontogenetic model according to which the brain regions that are the last to mature or develop are the first to be affected by aging (Raz 2005)....
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References
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TL;DR: Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals and was extended to elderly individuals the treatment strategy currently used in middle aged people.
3,162 citations
Journal Article•
TL;DR: Dementia is more prevalent in women, and AD is the main contributor to the steep increase of prevalence with age, so a large variation across studies was observed, as well as a difference in prevalence between men and women that was age dependent.
Abstract: Article abstract-The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men. There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries. This study confirms that AD is the most frequent dementing disorder in all ages, and that there is a higher incidence of dementia, specifically AD, in women than men among the very old. Finally, there may be regional differences in dementia incidence.
1,517 citations
TL;DR: It is found that those who received aerobic training showed substantial improvements in performance on tasks requiring executive control compared with anaerobically trained subjects.
Abstract: In the ageing process, neural areas1,2 and cognitive processes3,4 do not degrade uniformly. Executive control processes and the prefrontal and frontal brain regions that support them show large and disproportionate changes with age. Studies of adult animals indicate that metabolic5 and neurochemical6 functions improve with aerobic fitness. We therefore investigated whether greater aerobic fitness in adults would result in selective improvements in executive control processes, such as planning, scheduling, inhibition and working memory. Over a period of six months, we studied 124 previously sedentary adults, 60 to 75 years old, who were randomly assigned to either aerobic (walking) or anaerobic (stretching and toning) exercise. We found that those who received aerobic training showed substantial improvements in performance on tasks requiring executive control compared with anaerobically trained subjects.
1,340 citations
TL;DR: These findings extend the scope of beneficial effects of aerobic exercise beyond cardiovascular health, and they suggest a strong solid biological basis for the benefits of exercise on the brain health of older adults.
Abstract: Background. The human brain gradually loses tissue from the third decade of life onward, with concomitant declines in cognitive performance. Given the projected rapid growth in aged populations, and the staggering costs associated with geriatric care, identifying mechanisms that may reduce or reverse cerebral deterioration is rapidly emerging as an important public health goal. Previous research has demonstrated that aerobic fitness training improves cognitive function in older adults and can improve brain health in aging laboratory animals, suggesting that aerobic fitness may provide a mechanism to improve cerebral health in aging humans. We examined the relationship between aerobic fitness and in vivo brain tissue density in an older adult population, using voxel-based morphometric techniques. Methods. We acquired high-resolution magnetic resonance imaging scans from 55 older adults. These images were segmented into gray and white matter maps, registered into stereotaxic space, and examined for systematic variation in tissue density as a function of age, aerobic fitness, and a number of other health markers. Results. Consistent with previous studies of aging and brain volume, we found robust declines in tissue densities as a function of age in the frontal, parietal, and temporal cortices. More importantly, we found that losses in these areas were substantially reduced as a function of cardiovascular fitness, even when we statistically controlled for other moderator variables. Conclusions. These findings extend the scope of beneficial effects of aerobic exercise beyond cardiovascular health, and they suggest a strong solid biological basis for the benefits of exercise on the brain health of older adults. I N the course of normal aging, the human brain begins to lose tissue early in the third decade of life. Average losses are estimated at roughly 15% of the cerebral cortex and 25% of the cerebral white matter between ages 30 and 90 (1), with disproportionately high losses in the frontal, parietal, and temporal cortices (2). This pattern is closely matched by declines in cognitive performance throughout this period (3). Given the projected rapid growth in the aged population in developed countries (4), and the staggering costs associated with cognitive deterioration (4,5), identifying effective mechanisms to ward off structural and functional declines of the central nervous system (CNS) is rapidly emerging as an imperative public health goal. Several rigorous longitudinal studies (6,7) and a recent metaanalysis (8) have demonstrated that improvements in cardiovascular fitness can exert positive effects on human cognitive abilities. In this article, we report the first known evidence linking higher levels of aerobic fitness to the sparing of brain tissue in aging humans.
973 citations
University of California, San Diego1, Mayo Clinic2, New York University3, Georgetown University4, Rush University Medical Center5, University of Michigan6, Baylor College of Medicine7, Oregon Health & Science University8, Columbia University9, Eli Lilly and Company10, McGill University11, University of California, Irvine12, Yale University13, Medical University of South Carolina14, University of Alabama at Birmingham15, Brown University16
TL;DR: Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings.
Abstract: Background Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD. Objective To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial. Design Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial. Setting Memory disorder centers in the United States and Canada. Patients A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0. Main Outcome Measures Clinical, neuropsychologic, functional, neuroimaging, and genetic measures. Results Mean ± SD Alzheimer's Disease Assessment Scale–Cognitive Subscale scores were 5.6 ± 3.3 for controls, 11.3 ± 4.4 for patients with MCI, 18.0 ± 6.2 for the AD CDR 0.5 group, and 25.2 ± 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E ϵ4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD. Conclusions Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.
891 citations