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Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease.

Survival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer's disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD.

2545 related Products with: Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease.

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Mentally stimulating activities associate with better cognitive performance in Parkinson disease.

Subjects at risk of dementia benefit from participation in mentally stimulating activities, but no prior studies have investigated similar associations in Parkinson disease (PD). The aim of this study was to investigate the relationship between times spent engaging in mentally stimulating activities and cognitive functions in PD while accounting for the degree of primary neurodegenerations. PD patients (N = 41, 33 males; age 68.5 ± 7.2; Hoehn and Yahr stage 2.6 ± 0.6) completed the Community Health Activities Model Program for Seniors questionnaire, mini-mental state examination (MMSE), and [C]dihydrotetrabenazine dopaminergic and [C]piperidinyl propionate acetylcholinesterase PET imaging. The subset of mentally stimulating activity items of the Community Health Activities Model Program for Seniors questionnaire was used to develop a rating scale as primary outcome variable in this study. Findings showed that mean rating scale score of time spent in mentally stimulating activities over a 4-week timespan was 20.0 ± 8.3 h and mean MMSE score was 28.4 ± 1.9. Regression analysis showed that duration of participation in mentally stimulating activities was a significant predictor of MMSE scores (standardized β = 0.39, t = 2.8, p = 0.009; total model: F = 3.5, p = 0.005) independent from significant effects for cortical cholinergic activity (β = 0.35, t = 2.4, p = 0.024). Caudate nucleus dopaminergic activity, age, education, or duration of disease were not significant regressors. Post hoc analysis did not show significant effects of motor disease severity or level of physical activities. We conclude that engagement in mentally stimulating activities is associated with better cognitive abilities in PD, independent of education, severity of motor disease, nigrostriatal dopaminergic and cortical cholinergic degenerations.

1990 related Products with: Mentally stimulating activities associate with better cognitive performance in Parkinson disease.

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Plasma biomarkers are associated with agitation and regional brain atrophy in Alzheimer's disease.

This study investigated the relationships among plasma biomarkers, regional brain atrophy, and clinical symptoms in patients with Alzheimer's disease (AD; n = 177), mild cognitive impairment (MCI; N = 60) and controls (n = 108). The Mini-Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and Neuropsychiatric Inventory (NPI) subscales were administered to subjects. Magnetic resonance imaging was performed and medial temporal atrophy (MTA) and posterior atrophy (PA) were assessed visually. We examined associations among cognition, NPI score, plasma β-amyloid (Aβ) and clusterin levels, and regional brain atrophy in patients with AD by regression analysis. The mean MTA score was associated with the plasma Aβ1-42/Aβ1-40 ratio (r = 0.38, p = 0.01) and with MMSE scores (r = 0.43, p < 0.01). The plasma clusterin level was correlated with CDR sum of box and right-side PA scores (r = 0.28, p = 0.01 and r = 0.30, p = 0.03, respectively). Right-side PA scores were correlated significantly with NPI agitation/aggression (r = 0.30, p = 0.03) subscale scores. In conclusion, the plasma ratio of Aβ1-42/Aβ1-40 and clusterin level may be associated with different patterns of regional brain atrophy, which in turn may account for the clinical symptoms in patients with AD.

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Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease.

In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data.

2054 related Products with: Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease.

Beta Amyloid (42) ELISA K Beta Amyloid (1 40) ELISA Beta Amyloid (40) ELISA K Beta Amyloid (1 40) ELISA Anti 3 DG imidazolone Mon rHIV gp36, soluble Antige rHIV gp41, soluble Antige Liver disease spectrum ti Lung disease spectrum tis Colon disease spectrum ti Rectum disease spectrum ( Kidney disease spectrum (

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Mitochondrial transcription factor A (TFAM) rs1937 and AP endonuclease 1 (APE1) rs1130409 alleles are associated with reduced cognitive performance.

Mitochondrial dysfunction and DNA damage is intimately connected to ageing and neurodegeneration, including Alzheimer's disease (AD). A particular culprit in this context is oxidative stress, which is a result of increased reactive oxygen species (ROS) due to hyperactive or dysfunctional mitochondria and/or reduced DNA repair capacity. Base excision repair (BER) is the major pathway for repairing oxidative damage events in chromosomal and mitochondrial DNA. Defects in BER have been detected in ageing and neurodegeneration. Mitochondrial transcription factor A (TFAM) plays an important role in the maintenance of mitochondrial DNA integrity. The present study investigated single nucleotide polymorphisms (SNPs) in the genes encoding the BER components MutYH, OGG1, APE1, PolB and PolG and the gene encoding mitochondrial TFAM in a cohort of 161 AD patients, 96 non-AD patient controls (PC) and 192 healthy controls (HC). Notably, the minor allele carriers of APE1 rs1130409 and the common allele carriers of TFAM rs1937 were associated with reduced mini-mental state examination score in AD patients, PC and HC, with no distinction of SNP frequencies in either of these sub-groups. Collectively, the results suggest an association between DNA maintenance and decline in cognitive function. These studies enlighten the normal brain aging process and point to potential new biomarkers for cognitive function and impairment.

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Safety and Efficacy of Anti-Amyloid-β Immunotherapy in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Immunotherapeutics targeting amyloid-β (Aβ) have had mixed results in clinical trials. The present study aims to evaluate the safety and clinical efficacy of immunotherapeutic agents targeting Aβ in Alzheimer's disease. Randomised controlled trials of at least two weeks duration were included in the review. Fourteen randomised controlled trials (n = 5554) were identified in a systematic search of eight electronic databases. Upon pooling of data, there was no increased risk of any adverse event, serious adverse events, or death with the exception of a near fivefold increase in amyloid-related imaging abnormalities (ARIA; OR 4.79, 95% CI 1.24-18.55; p = 0.02). Of the cognitive indicators, the Mini-Mental State Examination (MMSE) showed a small statistically significant improvement (diff in means =0.44; p = 0.02), while the others (ADAS-cog, ADCS-ADL, and CDR-sb) showed no change. Therefore, immunotherapeutic agents have been relatively well tolerated, with some promise for cognitive improvements if the occurrence of ARIA can be mitigated.

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Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice.

Alzheimer's disease is a chronic and degenerative condition that had no treatment until recently. The current therapeutic strategies reduce progression of the disease but are expensive and commonly cause side effects that are uncomfortable for treated patients. Functional foods to prevent and/or treat many conditions, including neurodegenerative diseases, represent a promising field of study currently gaining attention. To this end, here we demonstrate the effects of pomegranate (Punica granatum) peel extract (PPE) regarding spatial memory, biomarkers of neuroplasticity, oxidative stress and inflammation in a mouse model of neurodegeneration. Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1-42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.- βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group. The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE. In conclusion, administration of pomegranate peel extract has neuroprotective effects involving multiple mechanisms to prevent establishment and progression of the neurodegenerative process induced by infusion with amyloid-β peptide in mice.

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Macrophages and dendritic cells in islets of Langerhans in diabetic autoimmunity: a lesson on cell interactions in a mini-organ.

Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets. In the absence of the CD103+ DC in the Batf3 deficient mice, autoimmunity never develops. We discuss the interactions among the two phagocytes and beta cells that result in autoimmune diabetes in NOD mice.

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Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer's disease.

To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD).

1329 related Products with: Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer's disease.

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Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system.

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained.

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