Efficacy of cognitive rehabilitation in Parkinson's disease

Cognitive rehabilitation is a potential and promising treatment for cognitive impairment in Parkinson＇s disease （PD） that has shown efficacy in diverse studies. In addition, some few studies have found brain changes after cognitive rehabilitation in PD, which supports the existence of brain plasticity associated to cognitive training in a degen- erative disease.

Consequences of redefining Alzheimer＇s disease in terms of amyloid burden without regard to cognitive decline

Alzheimer＇s disease（AD）redefined：For the past century,AD has been defined as a disease of progressive cognitive decline paired with a burden of amyloid-β（Aβ）plaques and pathologic tau tangles in the hippocampus and forebrain.However,a recent Framework paper jointly sponsored by the National Institute on Aging and the Alzheimer＇s Association（Jack et al.,2018）proposes new classification guidelines for AD,which,if adopted,will have profoundconsequences for the future management of AD.

Usefulness of the Japanese version of Rapid Dementia Screening Test for mild cognitive impairment in older patients with cardiovascular disease:a cross-sectional study

BACKGROUND Cognitive decline is common among older patients with cardiovascular disease(CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment(MCI) are not always feasible in clinical practice. Therefore, this study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test(RDST-J), which is a simple screening tool for identifying cognitive decline.METHODS This retrospective single-center study included patients who were ≥ 65 years old and hospitalized because of CVD.Patients with a pre-hospitalization diagnosis of dementia were excluded. Each patient's cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment(Mo CA-J), which is a standard tool for MCI screening. The correlation between the two scores was evaluated using Spearman's rank correlation coefficient. Receiver operating characteristic(ROC) analysis was also to evaluate whether the RDST-J could identify MCI, which was defined as a Mo CA-J score of ≤ 25 points.RESULTS The study included 78 patients(mean age: 77.2 ± 8.9 years). The RDST-J and Mo CA-J scores were strongly correlated(r = 0.835, P < 0.001). The ROC analysis revealed that an RDST-J score of ≤ 9 points provided 75.4% sensitivity and 95.2% specificity for identifying MCI, with an area under the curve of 0.899(95% CI: 0.835-0.964). The same cut-off value was identified when excluding patients with a high probability of dementia(RDST-J score of ≤ 4 points).CONCLUSIONS The RDST-J may be a simple and effective tool for identifying MCI in older patients with CVD.

Cognitive training in neurodegenerative diseases: a way to boost neuroprotective molecules?

Neurotrophins,and growth factors in general,are proteins which exert many actions in central nervous system neurons.Neurotrophins promote the survival and neuronal function of neurons and exert neuroprotective effects in pathological models of neurodegenerative diseases.In humans several clinical trials based on the use of these proteins have been carried out. Among them, it is worth to mention gene ther- apy especially in Parkinson＇s disease （PD） （Kordower and Bjorklund, 2013）, and a series of experiments using vectors capable of carrying neurotrophins in the selected target re- gion where they can exert their beneficial action （Ghosh et al., 2014）.

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

Long-term Helicobacter pylori Infection Does Not Induce Tauopathy and Memory Impairment in SD Rats

Helicobacter pylori（H.pylori） infection is a recognized risk factor of dementia, while its role and mechanism in Alzheimer disease（AD） remained unclarified. Our previous study has identified that injection of soluble H.pylori filtrate could induce AD-like pathologic changes and cognitive impairment in SD rats. In the present study, we further explored the effect of long-term stomach colonization of H.pylori bacteria on the brains of SD rats. The results showed that H.pylori bacteria gavage induced an efficient colonization of H.pylori in the stomach after four weeks. However, there was no significant change of tau phosphorylation at Thr205（pT205）, Thr231（pT231）, Ser396（pS396） and Ser404（pS404） sites in the hippocampus and cerebral cortex. The H.pylori-infected rats also showed no cognitive impairment. These observations may result from inefficient release of bacterial pathogenic factors or the overall lack of host inflammatory responses. We conclude that SD rat with long-term H.pylori colonization in the stomach is not a suitable animal model for exploring the effects of H.pylori infection on brain function in human beings; administration of bacterial filtrates may better reveal the systemic pathologic changes induced by bacterial infection in animals which show a negative host response to bacterial colonization.

Clustering and switching during a semantic verbal fluency test contribute to differential diagnosis of cognitive impairment

The verbal fluency test （VFT） can be dissociated into ＂clustering＂ （generating words within subcategories） and ＂switching＂ （shifting between clusters）, which may be valuable in differential diagnosis. In the current study, we investigated the validity of VFT in the differential diagnosis of Alzheimer＇s disease （AD, n = 65）, vascular dementia （VaD, n = 65）, mild cognitive impairment （MCI, n = 92）, and vascular cognitive impairment without dementia （VCIND, n = 76） relative to cognitively normal senior controls （NC, n = 374）. We found that in the NC group, the total correct score was significantly correlated with age and education; males generated more subcategories; cluster size increased with education, and subcategory and switching decreased with age. A significantly progressive advantage was observed in VFT scores in the sequence NC 〉 MCI/VCIND 〉 AD/VaD, and this significantly discriminated dementia patients from the other groups. AD patients performed better in all four VFT scores than VaD patients. Subcategory and switching scores significantly distinguished AD from VaD patients （AD 〉 VaD; mean difference, 0.50 for subcategory, P 〈0.05; 0.71 for switching, P 〈0.05）. MCI patients scored higher than VCIND patients, but the difference did not reach statistical significance. These results suggest that semantic VFT is useful for the detection of MCI and VCIND, and in the differential diagnosis of cognitive impairment.

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment（a MCI） to Alzheimer＇s disease（AD）. As a part of the medial temporal lobe memory system,the hippocampus is one of the brain regions affected earliest by AD neuropathology,and shows progressive degeneration as a MCI progresses to AD. Currently,no validated biomarkers can precisely predict the conversion from a MCI to AD. Therefore,there is a great need of sensitive tools for the early detection of AD progression. In this review,we summarize the specifi c structural and functional changes in the hippocampus from recent a MCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile,this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of a MCI to AD.