Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer’s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer’s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTESTenzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.

The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.

The benefits of physical exercise on improvements in brain-derived neurotrophic factor (BDNF) levels and cognitive functioning have been reported in the literature. However, the variability of individual responses may be linked to genetic differences. BDNF is considered one of the most plausible factors involved in the cognitive benefits associated with physical activity practice. A single nucleotide polymorphism localized in the gene that codes BDNF results in a missense mutation that promotes an amino acid substitution (Val66Met) in the protein. This process has been associated with decreased levels of BDNF secretion, with corresponding impairments in specific cognitive functions. Therefore, the objective of this study was to analyze the effects of a multimodal physical exercise program on peripheral BDNF levels and cognitive functions in elderly individuals with mild cognitive impairment (MCI). The participants were genotyped for the BDNF Val66Met polymorphism. Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) prior to and after the intervention. Forty-five participants were assigned to the control and trained groups. The trained group participated in a multimodal physical training for a 16-week period. The results showed a significant between-subjects interaction (p < 0.05), which indicates the beneficial contribution of training on cognitive functions independent of the BDNF genotype. However, only participants with BDNF-Met genotypes exhibited significant improvements in peripheral BDNF levels. The BDNF genotype appears to modulate the effects of physical exercise on BDNF secretion, but it does not influence cognition. This is the first study that evaluated the influence of a BDNF polymorphism on physical activity and cognition performance in elderly MCI individuals.

The benefits of physical exercise to reduce low-grade inflammation and improve Brain-Derived Neurotrophic Factor (BDNF) levels and cognitive function became a growing field of interest. Low-grade inflammation is common during aging and seems to be linked to neurodegenerative process. Regular physical exercises can help to reduce pro-inflammatory cytokines levels and to improve BDNF peripheral concentrations. The main goal of this research was to analyze the effects of a 16-week multimodal physical exercise program on peripheral BDNF levels and on Tumor Necrosis-α (TNF-α) and Interleukin- 6 (IL-6) as pro-inflammatory markers in cognitive healthy elderly individuals and in elderly with mild cognitive impairment (MCI). Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) prior to and after the intervention. Thirty cognitively healthy participants and thirty-seven MCI participants were assigned to the control (CG) and trained (TG) groups. The TG participated in a multimodal physical training program for a 16-week period. The results showed a significant between-subjects interaction, which indicates the beneficial contribution of training on the reduction of TNF-α (p=0.001) and IL-6 (p<0.001) and on the improvement of BDNF (p<0.001) peripheral concentrations. Cognitive functions also presented significant improvements for MCI trained group (p=0.03). In conclusion, physical exercise was effective to reduce pro-inflammatory cytokines and to improve BDNF peripheral levels, with positive reflexes on cognition. To the best of our knowledge, this is the first study that evaluated longitudinally the effects of a multimodal physical exercises protocol on peripheral concentrations of pro-inflammatory cytokines and cognition performance in elderly MCI individuals.

Background/Aims: Abnormal inflammatory response has been associated to the pathogenesis of Alzheimer’s disease (AD) and may be a marker of an ongoing neurodegenerative process. The aim of this study was to evaluate the serum levels of interleukin-1β (IL-1β) in patients with mild cognitive impairment (MCI) and AD. Methods: One hundred and sixty-three older adults (58 with mild to moderate AD, 74 with MCI and 31 healthy controls) were recruited for this study. Serum IL-1β levels were measured by ELISA. Patients with MCI were subcategorized in single-domain amnestic (aMCI), nonamnestic (naMCI), and multiple-domain (mdMCI) subtypes. Results: Patients with AD and MCI (all subtypes) had a significant increase in serum IL-1β levels as compared to controls (p = 0.03). Patients with mdMCI had serum IL-1β levels comparable to those with AD, and significantly higher than those observed in aMCI and naMCI (p = 0.02). Discussion: The present study provides evidence that inflammatory mechanisms, represented by elevated IL-1β, are observed in patients with MCI, specifically in those with impairment in multiple cognitive domains. As these patients are at higher risk of conversion to dementia, we propose that an increased serum IL-1β level is a stage marker of the ongoing brain neurodegeneration in the continuum between normal ageing and AD.

Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer's disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer's disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.

Decreased neurotrophic support, as indicated by a reduced systemic availability of BDNF, may play role in the neurodegenerative processes that underlie the continuum from MCI to AD. The presence of Met-BDNF allele, particularly in association with APOE*E4, may predict a worse cognitive outcome in patients with MCI.

Background Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression. Methods Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. Results Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission. Conclusion The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium’s clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.