Our groups recently published that a novel cyclic peptide (Naturido) modulates glia-neuron interactions in vitro and reverses aging-related deficits in senescence-accelerated mice. This article suggests that Naturido is a promising glia-neuron modulator for the treatment of not only senescence, but also Alzheimer’s disease (AD) and other neurodegenerative disorders. We briefly review the main points of this article.
Background: The relationship between awareness domains and behavioural-psychological symptoms in Alzheimer's disease (AD) is unclear.Objective: To investigate the effects of awareness domains on mild AD patients’ emotional-behavioural disturbances and caregivers’ stress accounting for demographic and clinical variables.Methods: Overall awareness and cognitive, emotional and functional domains were investigated in 60 mild AD patients and 60 related caregivers using the Questionnaire of identification of deficits. The patients’ cognitive functioning and psycho-affective/psychiatric symptoms, and their caregivers’ stress, were also assessed. Patients were classified as preserved (AD_AP) and impaired (AD_AI) awareness. Hierarchical linear models were applied to explore the effects of awareness domains on psychological and behavioural measures.Results: Unawareness was more frequent for emotional and functional disturbances than for cognitive deficits. AD_AP patients were less engaged in social and leisure activities and had higher rates of psycho-affective disturbances, while AD_AI had higher rates of psychiatric and behavioural disorders. Higher global awareness and higher awareness of cognitive alterations respectively explained 32% and 25 % of the variance for depression (both p: <0.001), higher awareness of emotional disturbances explained 23% of the variance for anxiety (p=0.022). Impaired awareness explained 33% of the variance for apathy symptom (p<0.001). Unawareness was also associated with higher caregivers’ stress.Conclusions: In mild AD patients, frequency of unawareness is domain-dependent. The relationship between awareness domains and emotional-behavioural disturbances is independent of demographic and clinical factors.
Investigating the mechanism of neuronal death in Alzheimer’s disease is difficult, because only a tiny percentage of neurons are degenerating at any time point during the long prodromal period. Epidemiological, genetic, biochemical and animal model studies have attributed excessive aldehyde load as a cause of Alzheimer neuronal death. Focusing on toxic aldehydes will help fill gaps in our knowledge that cannot be explained by the amyloid β or tau hypotheses. Hydroxynonenal is formed by peroxidation of membrane lipids and LDL or during deep-frying of vegetable oils. It carbonylates Hsp70.1, a heat shock protein with the dual functions of a chaperone protein and lysosomal stabilizer. Hydroxynonenal-mediated Hsp70.1 carbonylation followed by calpain-mediated cleavage of carbonylated Hsp70.1, causes lysosomal neuronal death (the ‘calpain-cathepsin hypothesis’). Aldehyde dehydrogenase (ALDH) participates in the removal of not only ethanol-derived acetaldehyde, but also linoleic acid-derived hydroxynonenal. This review describes how scavenging hydroxynonenal by ALDH enzymes prevent Alzheimer’s disease.
Alzheimer disease (AD) is the sixth leading cause of death, presently in America. AD is the centre of preoccupation of not only the scientific community, but also of the intelligentsia. The study of various structures of the brain, their connections and the pathways involved (anatomy), their normal functioning (physiology) and how this is subverted, leading to AD (pathology and pathogenesis), is vital to understanding comprehensively the complete gamut of clinical features of the Alzheimer disease. The anatomical structures, their connections and interplay, as implicated as having a role in AD, are briefly reviewed in this article. The functional significance with AD, of each structure is highlighted.
Background: As the Japanese society ages, the number of elderly people with dementia who commit criminal offenses is also increasing. Through a retrospective study of medical records, we investigated the relationship between dementia and antisocial behaviors in 239 outpatients who visited our psychiatric department during a 2-year period. Methods: We examined the medical records of outpatients of St. Marianna School of Medicine Hospital from April 2015 until March 2017: 152 with AD dementia (AD or AD+Vascular Dementia [VaD]), 19 with non-AD dementia (VaD, Lewy Body Dementia [LBD], FTD, alcohol-related dementia, organic dementia) and 24 controls without dementia. We investigated the incidence of antisocial behaviors and Behavioral and Psychological Symptoms of Dementia (BPSDs). We then compared their age, sex,, Hasegawa Dementia Scale-Revised (HDS-R) scores and the frequencies of antisocial behaviors and BPSDs using the chi-square test and analysis of variance. Results: The frequency of antisocial behaviors among all dementia patients in our study was 6.4%, with no significant difference versus the controls. Analysis of variance revealed that the antisocial behavior, home invasion was significantly more common in the non-AD group (5.3%) than in the AD and control groups (both 0%, p<0.05) and was significantly different between the AD and non-AD groups (p<0.05). Conclusion: We found a lower level of antisocial behaviors in people with dementia than reported in previous studies 7-9. The frequency of home invasion as an antisocial behavior and hallucinations and wandering as BPSDs was significantly higher in 1 patient with LBD (non-AD dementia). In this case, the hallucinations progressed to home invasion due to wandering. Antisocial behaviors with dementia mostly appear at the same time or after the development of BPSDs. Therefore, psychiatrists and caregivers should pay special attention to the treatment of BPSDs in patients with dementia to avoid the progression of these to antisocial behaviors.
Objective: This article presents a proof of concept study on the efficacy of autologous treatment with adipose tissue stromal cells and bone marrow stem cells on patients with mild Alzheimer’s disease.Methods: Eligible patients were selected on the basis of SPECT test, NINCDS-ADRDA criteria and specific inclusion and exclusion criteria. Cognitive status of the patients was assessed before and after autologous intrathecal administration of stem cells through different assessment tests. Neurological status was determined using PET scan, SPECT imaging and CSF protein analysis.Results: Steady improvement in the cognitive capability of patients was observed in the first six months of treatment. Later, there was a decline in the neurological ability which was revealed in the cognitive assessments. PET scan results were not changed.Conclusion: In mild AD patients, the effect was obvious although short lived. The enhancement of the general status of the patients revealed the therapeutic potential of the therapy. Future large-scale clinical trials with more study subjects to determine the safety and efficacy of the therapy in different clinical settings are warranted.
V dementia has been reported as the most common form of dementia in South Asian communities living in the UK due to higher incidences of hypertension and diabetes. Research on dementia care in these communities has highlighted the need for the need for cultural competency training for those working professionally with people with dementia and their families. It has been evidenced that while many health professionals feel that they need more training to both improve their knowledge about dementia and the cultural norms and religious practices of South Asian people with dementia, access to this sort of training is variable. Because of the acute lack of quantitative and qualitative data about the health and social care needs of South Asian communities and how they are best met, training to improve cultural competency in services is difficult. This paper reports the findings of research with Sikh carers of a family member with vascular dementia living in Wolverhampton in the UK highlighting evidence that demonstrates the diversity of the Sikh community and challenges assumptions of homogeneity. The evidence base presented highlights the importance for understanding the psycho-social perspectives of living with vascular dementia for migrant communities and the need for health care professionals and service managers to apply a person-centered approach to care. This paper will help participants to consider person centered care as a model for practice for achieving cultural competency with migrant communities living with dementia in their countries of work.
The most recent hypothesis of the development of small vessel vascular dementia (VaD) emphasises the role of blood-brain barrier (BBB) dysfunction. It is hypothesised that certain genetic polymorphisms of the BBB tight junction claudin-1 protein, in combination with adverse environmental risk factors, increase the risk of BBB dysfunction and small vessel VaD. In this case-control study, 97 control participants, with a mean Mini Mental State Exam (MMSE) score of 29.1, and 38 VaD participants were recruited and completed a questionnaire on their medical history and lifestyle factors. Blood was also collected and two single nucleotide polymorphisms (SNPs), rs17501010 and rs893051 of claudin-1 genotyping, were analysed by real-time polymerase chain reaction (PCR) assay. A significantly higher frequency of all rs893051 SNP genotypes (GC and CC) was found in the VaD population (OR=4.8, P=0.006 and OR=6, P<0.001 respectively). Patients with TT genotype of rs17501010 were also more likely to have VaD (OR=3.25, P=0.022). Stratification analysis revealed that having combined haplotype GC+ CC of rs893051 and lipid disorders was associated with higher risk of VaD (OR=9.9, P<0.001). For patients with type 2 diabetes the odds ratio of VaD increased significantly in GC+ CC genotypes of rs893051 (OR=12.57, P<0.0001) and GT+TT of rs17501010 (OR=5.33, P=0.01).
PURPOSE:To explore whether arterial spin labeling (ASL) imaging in cognitively intact elderly individuals may be used to predict subsequent early neuropsychological decline.MATERIALS AND METHODS:The local ethics committee approved this prospective study, and written informed consent was obtained from all participants. A total of 148 consecutive control subjects were included, 75 of whom had stable cognitive function (sCON) (mean age, 75.9 years ± 3.4 [standard deviation]; 43 female) and 73 of whom had deteriorated cognitive function (dCON) at 18-month clinical follow-up (mean age, 76.8 years ± 4.1; 44 female). An additional 65 patients with mild cognitive impairment (MCI) (mean age, 76.2 years ± 6.1; 25 female) were also included. Two-dimensional pulsed ASL was performed at the baseline visit. Statistical analysis included whole-brain voxelwise analysis of the ASL relative cerebral blood flow (CBF) data, receiver operating characteristic (ROC) curve analysis of the posterior cingulate cortex (PCC), and voxel-based morphometry analysis of gray matter.RESULTS:The voxelwise comparison of ASL revealed decreased relative CBF in the dCON group compared with that in the sCON group and slightly more pronounced relative CBF in the MCI group compared with that in the sCON group, most notably in the PCC (P < .05 corrected). Comparison of the dCON group with the MCI group revealed no significant differences. ROC analysis of relative CBF in the PCC enabled discrimination of dCON (P < .001; area under the ROC curve, 0.66). There was no confounding focal gray matter atrophy.CONCLUSION:Reduced ASL in the PCC at baseline is associated with the development of subsequent subtle neuropsychological deficits in healthy elderly control subjects. At a group level, ASL patterns in subjects with dCON are similar to those in patients with MCI at baseline, indicating that these subjects may initially maintain their cognitive status via mobilization of their neurocognitive reserve at baseline; however, they are likely to develop subsequent subtle cognitive deficits.
