Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-ADmini randomized controlled trial.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (ßLifestyle×Time = 1.11, P = 0.038; ßLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

Cochlear implant therapy improves the quality of life and social participation in the elderly: a prospective long-term evaluation.

PURPOSE: In recent years, the number of elderly cochlear implant (CI) candidates is continuously rising. In addition to the audiological improvement, other positive effects of CI treatment can also be observed in clinical routine. The "quality of life" as a parameter of success directly experienced by the patient is increasingly becoming the focus of clinical research. Although there are already clear indications of a rapid and significant improvement in quality of life, there is still a lack of systematic, prospectively collected longitudinal long-term data in patients over the age of 65. METHODS: This prospective longitudinal observational study included 31 patients between the age of 71 and 92 years who had first been treated unilaterally with a CI 6 years ago. In addition to free-field monosyllable recognition, quality of life was assessed using the World Health Organization Quality-of-Life Scale-old (WHOQL-OLD). The results were compared with the data from our previous study, in which we focused on the short- and medium-term effects on quality of life. In both studies, the same patient population was examined. In addition, these study data were compared with an age-matched average population. RESULTS: In speech recognition, there was no significant change from the control 6 months postoperatively compared with the results 6 years postoperatively. No significant changes occurred in the total quality of life score or any of the other six facets of quality of life when comparing the results 6 months postoperatively with the results 6 years postoperatively. In "Social participation", the CI patients even exceed the values of the age-matched average population 6 years after treatment. CONCLUSION: Improvement in the quality of life and especially in social participation appears stable over many years in elderly patients after hearing rehabilitation with a CI.

Age-related changes in energy metabolism in peripheral mononuclear blood cells (PBMCs) and the brains of cognitively healthy seniors.

Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1H- and 31P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (- 15%) and ATP levels (- 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (- 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (- 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant.

Long-term effects on the quality of life following cochlear implant treatment in older patients.

PURPOSE: Even in older patients, hearing rehabilitation with a cochlear implant has become an established method for deafened or severely hearing-impaired patients. In addition to the hearing improvement, numerous other effects of CI treatment can be observed in clinical routine. In the literature, there is multiple evidence for a rapid and significant improvement in quality of life with CI treatment. The aim of this study was to evaluate the long-term effects of hearing rehabilitation using CI on the quality of life in older patients (≥ 65 years). METHODS: This prospective cross-sectional study examined 84 patients between the age of 65 and 101 years who received unilateral CI treatment for the first time between one and 10 years ago. The World Health Organization Quality-of-Life Scale-Old (WHOQL-OLD) was used to determine the quality of life. The study cohort was divided into three groups to compare the quality of life over time: group I (1-3 years after CI treatment), group II (4-6 years after CI treatment), and group III (7-10 years after CI treatment). In addition, the data from this study were compared with the results of our previous study (Issing et al. 2020) in which we focused on the first 6 months after CI treatment. RESULTS: In all three groups, there was a significant improvement in monosyllabic discrimination within 1 year after CI fitting (p > 0.001). No significant differences were found between the three groups. There were no significant differences between the three groups in the WHOQOL-OLD total score (p = 0.487) or any of the other six facets. Moreover, no significant differences were found compared to the study group of our previous study 6 months after CI treatment. CONCLUSION: This study demonstrates the long-term stability of the improved quality of life following unilateral CI treatment in patients aged 65 years or older.

Impact of Hearing Rehabilitation Using Cochlear Implants on Cognitive Function in Older Patients.

OBJECTIVE: To assess the effects of hearing rehabilitation with cochlear implants on a subset of cognitive domains in older patients (≥65 yr). STUDY DESIGN: Prospective observational study. SETTING: Department of Oto-Rhino-Laryngology, Goethe-University Frankfurt/Main. PATIENTS: Patients aged between 65 and 86 years who have received unilateral cochlear implant (CI) therapy. INTERVENTION: Unilateral cochlear implantation. MAIN OUTCOME MEASURES: The dementia screening test (DemTect) and the trail making test (TMT) were carried out on three occasions: previous to the surgery, at the initial fitting (about 1 month after surgery) and 6 months after surgery. RESULTS: The average overall score on the DemTect scale increased significantly within 6 months of CI treatment (p = 0.049), with verbal aspects improving particularly markedly. The results of the trail making test showed that within 6 months of CI treatment, processing speed increased significantly (TMT A: p = 0.003; TMT B: p = 0.001). CONCLUSION: A pre-post comparison showed that aural rehabilitation with a CI results in an improvement in cognitive subdomains. Further comprehensive randomized-controlled studies may be necessary to evaluate possible confounding variables and to assess long-term results.

Cochlear Implant Therapy Improves the Quality of Life in Older Patients-A Prospective Evaluation Study.

OBJECTIVE: To determine the effects of cochlear implant (CI) hearing rehabilitation on quality of life in older patients (≥65 yr). STUDY DESIGN: Prospective observational study. SETTING: Department of Oto-Rhino-Laryngology, Medical University Frankfurt/Main. PATIENTS: Patients aged between 65 and 86 years who received unilateral CI therapy for the first time. INTERVENTION: Unilateral cochlear implantation. MAIN OUTCOME MEASURES: In addition to audiological parameters, the World Health Organization Quality-of-Life Scale - old (WHOQL-OLD) was used to assess quality of life prior to surgery, at the time of first fitting of the audio processor (approx. 1 mo after surgery) and 6 months afterward. Dementia and depression were excluded using dementia detection test (DemTect) and geriatric depression scale. RESULTS: Speech recognition improved significantly during the study period. Furthermore, the total WHOQL-OLD score showed a significant improvement of quality of life comparing the preoperative and the 6 months data (60.0 ±â€Š15.7 to 66.8 ±â€Š12.2 points) (p = 0.001). Only 6 months after surgery, comparable quality of life values were achieved compared to the corresponding population average of the same age group (67.96 ±â€Š14.74 points). No statistically significant difference remained between the study group and the age-adjusted population average (p = 0.37). CONCLUSION: To achieve auditory rehabilitation, CI treatment in older patients can be strongly recommended, not only hearing rehabilitation, but also to improve quality of life.

Is Objectively Assessed Sedentary Behavior, Physical Activity and Cardiorespiratory Fitness Linked to Brain Plasticity Outcomes in Old Age?

The aim of this cross-sectional study was to determine the associations of objectively assessed habitual physical activity and physical performance with brain plasticity outcomes and brain-derived neurotrophic factor (BDNF) levels in cognitively healthy older adults. Physical performance was analyzed based on cardiopulmonary exercise-testing data and accelerometer-based physical activity was analyzed as total activity counts, sedentary time, light physical activity and moderate to vigorous physical activity. Brain plasticity outcomes included magnetic resonance spectroscopy (MRS)-based markers, quantitative imaging-based hippocampal volume and BDNF serum levels. The association between physical performance and hippocampal volume was strongly influenced by participants' education, sex, age and BMI. Confounder-controlled correlation revealed significant associations of brain plasticity outcomes with physical activity but not with performance. MRS-based adenosine triphosphate to phosphocreatine and glycerophosphocholine to phosphocreatine ratios were significantly associated with accelerometer total activity counts. BDNF was detrimentally associated with sedentary time but beneficially related to accelerometer total activity counts and moderate to vigorous physical activity. Exceeding the current moderate to vigorous physical activity recommendations led to significantly higher BDNF levels. Our results indicate that regular physical activity might be beneficial for preserving brain plasticity in higher age. In this study these associations were not mediated significantly by physical performance. Overall physical activity and exceeding current moderate to vigorous physical activity recommendations were positively associated with BDNF. Sedentary behavior, however, seems to be negatively related to neurotrophic factor bioavailability in the elderly.

SMART: physical activity and cerebral metabolism in older people: study protocol for a randomised controlled trial.

BACKGROUND: Physical activity exerts a variety of long-term health benefits in older adults. In particular, it is assumed to be a protective factor against cognitive decline and dementia. METHODS/DESIGN: Randomised controlled assessor blinded 2-armed trial (n = 60) to explore the exercise- induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age ≥ 65), recruited within the setting of assisted living facilities and newspaper advertisements are allocated to a 12-week individualised aerobic exercise programme intervention or a 12-week waiting control group. Total follow-up is 24 weeks. The main outcome is the change in cerebral metabolism as assessed with Magnetic Resonance Spectroscopic Imaging reflecting changes of cerebral N-acetyl-aspartate and of markers of neuronal energy reserve. Imaging also measures changes in cortical grey matter volume. Secondary outcomes include a broad range of psychometric (cognition) and movement-related parameters such as nutrition, history of physical activity, history of pain and functional diagnostics. Participants are allocated to either the intervention or control group using a computer-generated randomisation sequence. The exercise physiologist in charge of training opens sealed and opaque envelopes and informs participants about group allocation. For organisational reasons, he schedules the participants for upcoming assessments and exercise in groups of five. All assessors and study personal other than exercise physiologists are blinded. DISCUSSION: Magnetic Resonance Spectroscopic Imaging gives a deeper insight into mechanisms of exercise-induced changes in brain metabolism. As follow-up lasts for 6 months, this study is able to explore the mid-term cerebral metabolic effects of physical activity assuming that an individually tailored aerobic ergometer training has the potential to counteract brain ageing. TRIAL REGISTRATION: NCT02343029 (clinicaltrials.gov; 12 January 2015).