Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts.

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m2 and <75% of baseline rate. RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I2=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m2), hypertension, diabetes, and coronary heart disease at baseline. CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

Characterising Australian memory clinics: current practice and service needs informing national service guidelines.

BACKGROUND: Memory clinics (MCs) play a key role in accurate and timely diagnoses and treatment of dementia and mild cognitive impairment. However, within Australia, there are little data available on current practices in MCs, which hinder international comparisons for best practice, harmonisation efforts and national coordination. Here, we aimed to characterise current service profiles of Australian MCs. METHODS: The 'Australian Dementia Network Survey of Expert Opinion on Best Practice and the Current Clinical Landscape' was conducted between August-September 2020 as part of a larger-scale Delphi process deployed to develop national MC guidelines. In this study, we report on the subset of questions pertaining to current practice including wait-times and post-diagnostic care. RESULTS: Responses were received from 100 health professionals representing 60 separate clinics (45 public, 11 private, and 4 university/research clinics). The majority of participants were from clinics in metropolitan areas (79%) and in general were from high socioeconomic areas. While wait-times varied, only 28.3% of clinics were able to offer an appointment within 1-2 weeks for urgent referrals, with significantly more private clinics (58.3%) compared to public clinics (19.5%) being able to do so. Wait-times were less than 8 weeks for 34.5% of non-urgent referrals. Only 20.0 and 30.9% of clinics provided cognitive interventions or post-diagnostic support respectively, with 7.3% offering home-based reablement programs, and only 12.7% offering access to group-based education. Metropolitan clinics utilised neuropsychological assessments for a broader range of cases and were more likely to offer clinical trials and access to research opportunities. CONCLUSIONS: In comparison to similar countries with comprehensive government-funded public healthcare systems (i.e., United Kingdom, Ireland and Canada), wait-times for Australian MCs are long, and post-diagnostic support or evidence-based strategies targeting cognition are not common practice. The timely and important results of this study highlight a need for Australian MCs to adopt a more holistic service of multidisciplinary assessment and post-diagnostic support, as well as the need for the number of Australian MCs to be increased to match the rising number of dementia cases.

The many ages of man: diverse approaches to assessing ageing-related biological and psychological measures and their relationship to chronological age.

PURPOSE OF REVIEW: Chronological age is a crude measure and may not be the best indicator of the ageing process. Establishing valid and reliable biomarkers to understand the true effect of ageing is of great interest. We provide an overview of biological and psychological characteristics that change with age and can potentially serve as markers of the ageing process, and discuss if an integration of these characteristics may more accurately measure the true age of a person. We also describe the clinicopathological continuum of these ageing-related changes. RECENT FINDINGS: Ageing-related changes in the biological and psychological systems of the body have been studied to varying degrees and with differing emphases. Despite the development of ageing indices, there is no single indicator that can holistically estimate the ageing process. Differential ageing of bodily systems remains poorly understood, and valid methods have not been developed for composite markers of biological and psychological processes. SUMMARY: The ageing process is complex and heterogeneous. Incorporating biological and psychological measures may improve accuracy in reflecting an individual's 'true age,' and elucidate why some people age successfully, whereas others show ageing-related decline and disease.

Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer's disease.

PURPOSE OF REVIEW: The current review discusses the biology and metabolism of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+) in the central nervous system. We also review recent work suggesting important neuroprotective effects that may be associated with the promotion of NAD+ levels through NAD+ precursors against Alzheimer's disease. RECENT FINDINGS: Perturbations in the physiological homoeostatic state of the brain during the ageing process can lead to impaired cellular function, and ultimately leads to loss of brain integrity and accelerates cognitive and memory decline. Increased oxidative stress has been shown to impair normal cellular bioenergetics and enhance the depletion of the essential nucleotides NAD+ and ATP. NAD+ and its precursors have been shown to improve cellular homoeostasis based on association with dietary requirements, and treatment and management of several inflammatory and metabolic diseases in vivo. Cellular NAD+ pools have been shown to be reduced in the ageing brain, and treatment with NAD+ precursors has been hypothesized to restore these levels and attenuate disruption in cellular bioenergetics. SUMMARY: NAD+ and its precursors may represent an important therapeutic strategy to maintain optimal cellular homoeostatic functions in the brain. NAD+ precursors are available in a variety of foods and may be translated to the clinic in the form of supplements.

The Antidepressant Effect of Laser Acupuncture: A Comparison of the Resting Brain's Default Mode Network in Healthy and Depressed Subjects During Functional Magnetic Resonance Imaging.

BACKGROUND: It has been suggested that the antidepressant effect of laser acupuncture involves modulation of the default mode network (DMN) or resting state network (RSN). In this study, the authors investigated changes in the DMN during laser acupuncture in depressed and nondepressed participants. OBJECTIVE: To aim of this study was to determine if the modulation of the DMN effects by laser acupuncture in depressed participants are different from those of nondepressed participants. DESIGN: Randomized stimulation was performed with laser acupuncture on four putative antidepressant acupoints (LR 14, LR 8, CV 14, and HT 7) in a block on-off design, while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from each subject's whole brain on a 3T scanner. DMN patterns of the participants were identified, using an independent component analysis. The identified DMN components from both the nondepressed group and the depressed group were then analytically compared using SPM5. SETTING: This study took place at a research institute. SUBJECTS: Ten nondepressed participants and 10 depressed participants (DS) as confirmed by the Hamilton Depression Rating Scale (HAM-D) participated in this study. INTERVENTION: Low Intensity Laser Acupuncture. MAIN OUTCOME MEASURES: Significant DMN patterns in one group were greater than those in the other group. RESULTS: The nondepressed participants had significant modulation of DMN in the frontal region at the medial frontal gyrus (verum laser>rest, p<0.001) for three acupoints (LR 14, LR 8, and CV 14). For the depressive participants, the DMN modulation occurred at the inferior parietal cortex and the cerebellum (verum laser>rest, p<0.001). CONCLUSIONS: Laser acupuncture on LR 8, LR 14, and CV 14 stimulated both the anterior and posterior DMN in both the nondepressed and depressed participants. However, in the nondepressed participants, there was consistently outstanding modulation of the anterior DMN at the medial frontal gyrus across all three acupoints. In the depressed participants, there was wider posterior DMN modulation at the parieto-temporal-limbic cortices. This is part of the antidepressant effect of laser acupuncture.

The brain effects of laser acupuncture in healthy individuals: an FMRI investigation.

BACKGROUND: As laser acupuncture is being increasingly used to treat mental disorders, we sought to determine whether it has a biologically plausible effect by using functional magnetic resonance imaging (fMRI) to investigate the cerebral activation patterns from laser stimulation of relevant acupoints. METHODOLOGY/PRINCIPAL FINDINGS: Ten healthy subjects were randomly stimulated with a fibreoptic infrared laser on 4 acupoints (LR14, CV14, LR8 and HT7) used for depression following the principles of Traditional Chinese Medicine (TCM), and 1 control non-acupoint (sham point) in a blocked design (alternating verum laser and placebo laser/rest blocks), while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from the whole brain on a 3T scanner. Many of the acupoint laser stimulation conditions resulted in different patterns of neural activity. Regions with significantly increased activation included the limbic cortex (cingulate) and the frontal lobe (middle and superior frontal gyrus). Laser acupuncture tended to be associated with ipsilateral brain activation and contralateral deactivation that therefore cannot be simply attributed to somatosensory stimulation. CONCLUSIONS/SIGNIFICANCE: We found that laser stimulation of acupoints lead to activation of frontal-limbic-striatal brain regions, with the pattern of neural activity somewhat different for each acupuncture point. This is the first study to investigate laser acupuncture on a group of acupoints useful in the management of depression. Differing activity patterns depending on the acupoint site were demonstrated, suggesting that neurological effects vary with the site of stimulation. The mechanisms of activation and deactivation and their effects on depression warrant further investigation.

Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation.

BACKGROUND: To determine the efficacy and tolerability of repetitive transcranial magnetic stimulation (rTMS) as a treatment for obsessive compulsive disorder (OCD) in a double-blind placebo-controlled study. METHOD: Subjects with treatment-resistant OCD were randomized to rTMS (n = 10) or sham rTMS (n = 8) for 10 sessions of daily stimulation over the left dorsolateral prefrontal cortex (DLPFC), with subjects and raters being blind to the treatment. Subjects were offered an open extension of up to 20 sessions of rTMS. RESULTS: The two groups did not differ on change in Yale-Brown Obsessive Compulsive Scale (YBOCS) or Maudsley Obsessive-Compulsive Inventory scores over 10 sessions, with or without correction for depression ratings. Over 20 sessions, there was a significant reduction in total YBOCS scores, but not after controlling for depression. rTMS over 20 sessions was well tolerated. CONCLUSION: Two weeks of rTMS over the left DLPFC is ineffective for treatment-resistant OCD.

Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy.

Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.

Differential effects of transcranial magnetic stimulation of left and right posterior parietal cortex on mental rotation tasks.

A recently published study used the interference strategy of transcranial magnetic stimulation (TMS) to demonstrate the role of the right posterior parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used similar stimulation parameters over the same left and right PPC regions, and examined the ability to rotate more complex 3D Shepard and Metzler (1971) images. There was reduced accuracy of performance with both right and left PPC stimulation for different angles of rotation of the visual stimuli. Right PPC stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC stimulation affected 180 degrees C rotation. We hypothesise that the two hemispheres make different contributions to the processing underlying visuospatial mental imagery: the right PPC is important for spatial rotations through smaller angles; the left hemisphere has a unique role when the stimuli to be compared are rotated through 180 degrees C, a task that engages verbal strategies due to the well-documented special nature of enantiomorphs.