Chao Suo

The Study of Mental and Resistance Training (SMART) study—resistance training and/or cognitive training in mild cognitive impairment: a randomized, double-blind, double-sham controlled trial.

BACKGROUND Mild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available. METHODS The Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2-3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimers Disease Assessment Scale-cognitive subscale; ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores. RESULTS One hundred adults with MCI [70.1 (6.7) years; 68% women] were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog; [relative effect size (95% confidence interval) -0.33 (-0.73, 0.06); P < .05] at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices; P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training [P < .03; odds ratio (95% confidence interval) 3.50 (1.18, 10.48)]. Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training [z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (-0.60, 0.28) combined] and 48% higher (P < .04) for Global Domain [z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined]. CONCLUSIONS Resistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months.

A longitudinal study of brain atrophy over two years in community-dwelling older individuals

Most previous neuroimaging studies of age-related brain structural changes in older individuals have been cross-sectional and/or restricted to clinical samples. The present study of 345 community-dwelling non-demented individuals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippocampus. In some regions, such as left and right entorhinal cortices, right hippocampus and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimers disease (AD).

Hippocampal harms, protection and recovery following regular cannabis use

Shifting policies towards legalisation of cannabis for therapeutic and recreational use raise significant ethical issues for health-care providers seeking evidence-based recommendations. We investigated whether heavy cannabis use is associated with persistent harms to the hippocampus, if exposure to cannabidiol offers protection, and whether recovery occurs with abstinence. To do this, we assessed 111 participants: 74 long-term regular cannabis users (with an average of 15.4 years of use) and 37 non-user healthy controls. Cannabis users included subgroups of participants who were either exposed to Δ9-tetrahydrocannabinol (THC) but not to cannabidiol (CBD) or exposed to both, and former users with sustained abstinence. Participants underwent magnetic resonance imaging from which three measures of hippocampal integrity were assessed: (i) volume; (ii) fractional anisotropy; and (iii) N-acetylaspartate (NAA). Three curve-fitting models across the entire sample were tested for each measure to examine whether cannabis-related hippocampal harms are persistent, can be minimised (protected) by exposure to CBD or recovered through long-term abstinence. These analyses supported a protection and recovery model for hippocampal volume (P=0.003) and NAA (P=0.001). Further pairwise analyses showed that cannabis users had smaller hippocampal volumes relative to controls. Users not exposed to CBD had 11% reduced volumes and 15% lower NAA concentrations. Users exposed to CBD and former users did not differ from controls on any measure. Ongoing cannabis use is associated with harms to brain health, underpinned by chronic exposure to THC. However, such harms are minimised by CBD, and can be recovered with extended periods of abstinence.

Study of Mental Activity and Regular Training (SMART) in at risk individuals: a randomised double blind, sham controlled, longitudinal trial.

BackgroundThe extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects.MethodsSMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk × 6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimers Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS).DiscussionSMART will provide a novel evaluation of the immediate and long term benefits of CT, PRT, and combined CT and PRT on global cognitive function and brain morphology, as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline.Trial RegistrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000489392

Supervisory experience at work is linked to low rate of hippocampal atrophy in late life

Cultivation of an active cognitive lifestyle, including diverse and challenging educational, occupational and cognitively-loaded leisure activities may be protective against development of dementia but the mechanisms underlying this link are not clear. We used the Lifetime Experiences Questionnaire (LEQ) to assess the structural brain correlates of cognitive lifestyle in the Sydney Memory and Aging Study, a large population-based cohort of originally 1037 non-demented elderly aged over 70 years of age. After excluding those without structural Magnetic Resonance Image data or Mild Cognitive Impairment at their most recent assessment, 151 cognitively intact subjects were studied. Whole-brain voxel based morphometric analysis found that higher total Lifetime Experiences Questionnaire scores are linked with increased grey matter volume in the medial temporal lobe, especially in the hippocampus. Through a series of more specific analyses, we found that supervisory and managerial experience in midlife was the dominant contributor to this effect. Furthermore, in those with longitudinal neuroimaging data (N=91), we measured hippocampal structural changes over a 2-3 year period by gold-standard manual tracing. The rate of hippocampal atrophy in late-life in those with high level supervisory experience in midlife was five-times slower than those with no midlife supervisory experience (p<0.001). Individual differences in intracranial volume, age, gender, physical activity, depressive symptoms, or apolipoprotein ε4 genetic status could not explain these findings, nor could specific lifestyle patterns in late life. For the first time, we reveal that managerial and supervisory experience during our working life is connected to hippocampal integrity after retirement, some 20-30 years later. Our results stimulate several questions about the nature of work-related effects on longterm behaviour, structural neuroplasticity and neuroprotection, and may help explain differences in dementia-risk based on cognitive lifestyle.

Cognitive training-induced short-term functional and long-term structural plastic change is related to gains in global cognition in healthy older adults: a pilot study.

Computerized cognitive training (CCT) is a safe and inexpensive intervention to enhance cognitive performance in the elderly. However, the neural underpinning of CCT-induced effects and the timecourse by which such neural changes occur are unknown. Here, we report on results from a pilot study of healthy older adults who underwent three 1-h weekly sessions of either multidomain CCT program (n = 7) or an active control intervention (n = 5) over 12 weeks. Multimodal magnetic resonance imaging (MRI) scans and cognitive assessments were performed at baseline and after 9 and 36 h of training. Voxel-based structural analysis revealed a significant Group × Time interaction in the right post-central gyrus indicating increased gray matter density in the CCT group compared to active control at both follow-ups. Across the entire sample, there were significant positive correlations between changes in the post-central gyrus and change in global cognition after 36 h of training. A post-hoc vertex-based analysis found a significant between-group difference in rate of thickness change between baseline and post-training in the left fusiform gyrus, as well as a large cluster in the right parietal lobe covering the supramarginal and post-central gyri. Resting-state functional connectivity between the posterior cingulate and the superior frontal gyrus, and between the right hippocampus and the superior temporal gyrus significantly differed between the two groups after 9 h of training and correlated with cognitive change post-training. No significant interactions were found for any of the spectroscopy and diffusion tensor imaging data. Though preliminary, our results suggest that functional change may precede structural and cognitive change, and that about one-half of the structural change occurs within the first 9 h of training. Future studies are required to determine the role of these brain changes in the mechanisms underlying CCT-induced cognitive effects.

Differential brain effects of laser and needle acupuncture at LR8 using functional MRI

Objective While needle acupuncture is a well-accepted technique, laser acupuncture is being increasingly used in clinical practice. The differential effects of the two techniques are of interest. We examine this in relation to brain effects of activation of LR8, a putative acupuncture point for depression, using functional MRI (fMRI). Methods Sixteen healthy participants were randomised to receive low intensity laser acupuncture to LR8 on one side and needle acupuncture to the contralateral LR8. Stimulation was in an on-off block design and brain patterns were recorded under fMRI. Results Significant activation occurred in the left precuneus during laser acupuncture compared with needle acupuncture and significant activation occurred in the left precentral gyrus during needle acupuncture compared with laser acupuncture. Conclusions Laser and needle acupuncture at LR8 in healthy participants produced different brain patterns. Laser acupuncture activated the precuneus relevant to mood in the posterior default mode network while needle acupuncture activated the parietal cortical region associated with the primary motor cortex. Further investigations are warranted to evaluate the clinical relevance of these effects.

The neurobiology of cannabis use disorders: A call for evidence

1 School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, VIC, Australia, 2 Addiction Development and Psychopathology Lab, Department of Psychology, University of Amsterdam, Amsterdam, Netherlands, 3 School of Psychology, Centre for Health Initiatives and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia, Department of Psychological Science, College of Arts and Sciences, The University of Vermont, Burlington, VT, USA

Mediation of Cognitive Function Improvements by Strength Gains After Resistance Training in Older Adults with Mild Cognitive Impairment: Outcomes of the Study of Mental and Resistance Training

To determine whether improvements in aerobic capacity (VO2peak) and strength after progressive resistance training (PRT) mediate improvements in cognitive function.

Low incidence of melanoma brain metastasis in the hippocampus.

AIMS ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of whole brain radiation therapy (WBRT) after local treatment of 1-3 melanoma brain metastases. Modern radiation therapy technologies can now conformally spare the hippocampus during WBRT and therefore potentially reduce the risk of neurocognitive deficit. The aims of this study were to report the prevalence of melanoma metastases within the hippocampal sparing region and to identify variables that correlate with the presence of metastases within the hippocampal sparing region. METHODS The pre-local treatment MRI scans of 77 eligible WBRTMel patients were used to contour the individual metastasis and the hippocampus. The volume, location and closest distance of each metastasis to the hippocampus were recorded. Binary logistic regression was performed to assess the influence of factors on the location of a metastasis within 5mm of the hippocampus. RESULTS The median age was 61 and 66% were male. The distribution of the 115 metastases was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median aggregate volume of the metastasis was 3516mm(3). None of the metastases were within the hippocampus. Four patients (5.2%) had metastases within 5mm of the hippocampus. The median distance from metastasis to the nearest hippocampus was 37.2mm. Only the total volume of metastases was a significant predictor for the risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI: 1.003-1.144, p=0.040). CONCLUSIONS This study confirmed a low incidence of melanoma metastasis in the hippocampal sparing region at diagnosis. Given the lack of randomized data on the safety and benefit of hippocampal sparing WBRT, the current WBRTMel trial provides the opportunity to explore the feasibility of this technique.