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\"Brain aging has long been seen as a process of deterioration and decline. Today, this view been challenged with research showing that not all cognitive processes decline with age, that some improve over the course of adulthood, and those that improve can often compensate for those that decline. Chapters in this multidisciplinary volume examine the neural mechanisms underlying changes in the aging brain, changes in learning and memory, risk and protective factors, and the assessment and prevention of cognitive decline\"--Provided by publisher.

Background A better insight into older adults’ understanding of and attitude towards cognitive disorders and their prevention, as well as expectations and reasons for participation in prevention trials, would help design, conduct, and implement effective preventive interventions. This qualitative study aimed at exploring the knowledge and perceptions of cognitive disorders and their prevention among participants in a prevention trial. Methods Semi-structured interviews were conducted among the participants of a multinational randomised controlled trial testing the efficacy of a lifestyle-based eHealth intervention in preventing cardiovascular disease or cognitive decline in community dwellers aged 65+. Participants were probed on their reasons for participation in the trial and their views on general health, cardiovascular disease, ageing, and prevention. The subset of data focusing on cognitive disorders (15 interviewees; all in Finland) was considered for this study. Data were analysed using content analysis. Results Participants’ knowledge of the cause and risk factors of cognitive disorders and prevention was limited and superficial, and a need for up-to-date, reliable, and practical information and advice was expressed. Cognitive disorders evoked fear and concern, and feelings of hopelessness and misery were frequently expressed, indicating a stigma. Strong heredity of cognitive disorders was a commonly held belief, and opinions on the possibility of prevention were doubtful, particularly in relation to primary prevention. Family history and/or indirect experiences of cognitive disorders was a recurrent theme and it showed to be linked to both the knowledge of and feelings associated with cognitive disorders, as well as attitude towards prevention. Indirect experiences were linked to increased awareness and knowledge, but also uncertainty about risk factors and possibility of prevention. Distinct fear and concerns, particularly over one’s own cognition/risk, and high motivation towards engaging in prevention and participating in a prevention trial were also identified in connection to this theme. Conclusions Family history and/or indirect experiences of cognitive disorders were linked to sensitivity and receptiveness to brain health and prevention potential. Our findings may be helpful in addressing older adults’ expectations in future prevention trials to improve recruitment, maximise adherence, and facilitate the successful implementation of interventions.

Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70–84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (–0·200 [95% CI –0·256 to –0·144] in the hearing intervention group and –0·202 [–0·258 to –0·145] in the control group; difference 0·002 [–0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. US National Institutes of Health.

A 3-year trial involving persons with a family history of dementia showed no differences in cognitive change or brain MRI outcomes between the MIND diet, designed for neuroprotection, and a control diet.

INTRODUCTION We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster‐randomized trial. METHODS Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain‐specific neuropsychological tests). RESULTS Of 1030 participants at baseline, n = 819 completed the 24‐month follow‐up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: –0.113, 0.133) were found between groups at follow‐up. Perceived restrictions in intervention conduct by the COVID‐19 pandemic did not impact intervention effectiveness. DISCUSSION The intervention did not improve global cognitive performance. Highlights Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health‐related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID‐19 pandemic.

Cognitive frailty is defined as the presence of both physical frailty and cognitive impairment (clinical dementia rating score = 0.5), in the absence of dementia. It is characterized by concurrent physical frailty and potentially reversible cognitive impairment. In this study, we sought to elucidate the effects of high-speed resistance exercise training on cognitive function and physical performance in older adults with cognitive frailty. We conducted a parallel-group, randomized controlled trial involving community-living older adults with cognitive frailty. The participants' mean age was 73.9 (± 4.3 SD) years, and 69.8% (n=30) were female. Two different 4-month interventions included high-speed resistance exercise training group (n=22) and a control group (balance and band stretching, n=23). Frailty score, cognitive function (memory, processing speed, cognitive flexibility, working memory, executive function), physical function (SPPB, TUG, gait speed), and muscle strength (grip strength, knee extension strength) were assessed at baseline, 8 weeks, and 16 weeks. Statistical analysis showed that exercise improved performance significantly in the tests for cognitive function (processing speed and executive function, both p < 0.05), physical function (SPPB, TUG, gait speed, both p < 0.05), and muscle strength (grip strength, knee extension strength, both p < 0.05). However, no significant changes in frailty score were observed between intervention and either control group (p < 0.05). In conclusion, our findings indicate that high-speed resistance exercise training approaches are effective in improving cognitive function and physical performance in older adults with cognitive frailty. This study shows that it is feasible to identify older adults with cognitive frailty in the community and primary care setting for effective intervention to reduce their level of frailty and cognitive impairment.

INTRODUCTION We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI). METHODS Participants aged 65‐85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months. RESULTS Of 531 participants, 406 completed the trial. The between‐group difference in composite score changes was 0.047 (95% CI: −0.029 to 0.124). Secondary analyses indicated positive impacts of interventions on several secondary health outcomes. The interventions appeared to be particularly effective for individuals with high attendance during exercise sessions and those with the apolipoprotein E ε4 allele and elevated plasma glial fibrillary acidic protein levels. DISCUSSION The multidomain intervention showed no efficacy in preventing cognitive decline. Further research on more efficient strategies and suitable target populations is required. Highlights This trial evaluated the efficacy of multidomain intervention in individuals with MCI. The trial did not show a significant difference in preplanned cognitive outcomes. Interventions had positive effects on a wide range of secondary health outcomes. Those with adequate adherence or high risk of dementia benefited from interventions.

Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT. SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov, NCT01206062. From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7–5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of −0·005 (95% CI −0·010 to 0·001) in the intensive treatment group and −0·001 (–0·006 to 0·005) in the standard treatment group (between-group difference −0·004, 95% CI −0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference −0·010, 95% CI −0·017 to −0·002; p=0·02), with an annual decline of −0·025 (–0·030 to −0·019) for the intensive treatment group and −0·015 (–0·021 to 0·009) for the standard treatment group. Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains. National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.

Multidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age. Brain-derived neurotrophic factor (BDNF) is essential for experience-dependent plasticity and increases following physical exercise, suggesting that physical exercise may facilitate subsequent learning. In a randomized-controlled trial, healthy older adults (65–75 years) completed a 12-week behavioral intervention that involved either physical exercise immediately before cognitive training ( n  = 25; 13 females), physical exercise immediately after cognitive training ( n  = 24; 11 females), physical exercise only ( n  = 27; 15 females), or cognitive training only ( n  = 21; 12 females). We hypothesized that cognition would benefit more from cognitive training when preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF and cognitive training outcome would be greater when cognitive training is preceded by physical exercise. Greater increases of plasma BDNF were associated with greater cognitive training gains on trained task paradigms, but only when such increases preceded cognitive training (ß = 0.14, 95% CI [0.04, 0.25]). Average cognitive training outcome did not differ depending on intervention order (ß = 0.05, 95% CI [−0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning at an interindividual level in older adults, with implications for future multidomain lifestyle interventions.