This article reports 2 cases of urinary retention in Alzheimer's disease with agitation treated by acupuncture. Based on patients' clinical symptoms, the etiology and pathogenesis were determined, and acupuncture was applied to Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), and bilateral Ciliao (BL32), Zhongliao (BL33), Fengchi (GB20), Taiyang (EX-HN5), etc. to regulate the mind and promote water metabolism. The positive and negative electrodes of the SDZ-Ⅴ type electroacupuncture device were attached to ipsilateral Ciliao (BL32), Zhongliao (BL33) respectively, with continuous wave, at the frequency of 15 Hz, and the current of 3 to 10 mA, depending on patients' tolerance. The needles were retained for 20 min. The treatment was delivered once every other day, 3 interventions a week and 12 interventions as 1 course. Both patients reported the micturition desire after 1 intervention with acupuncture and the catheter was removed on the same day. The urination was ameliorated without dysuresia after 1-2 courses of treatment, and the agitated behavior was alleviated. It can be the reference for the clinical treatment of urinary retention in patients with Alzheimer's disease with agitation.
Humans ; Alzheimer Disease/psychology* ; Acupuncture Therapy ; Urinary Retention/etiology* ; Male ; Female ; Aged ; Acupuncture Points ; Psychomotor Agitation/complications*

Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer's disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.
Humans ; Hypotension/complications* ; Cognitive Dysfunction/etiology* ; Alzheimer Disease/epidemiology* ; Cerebrovascular Circulation/physiology* ; Cognition Disorders/etiology*

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Periodontal diseases are inflammatory diseases caused by oral pathogens around the periodontal supporting tissues, leading to systemic and chronic inflammatory conditions. The continuous chronic systemic inflammation may be a trigger of neuroinflammation, which is the prominent feature of a variety of neurological disorders. It implies that there may be a causal link between periodontal diseases and neurological disorders. This article presents epidemiological and biological evidences that periodontal diseases can induce or exacerbate neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis and major depressive disorder, and analyzes the possible mechanisms. The importance of maintaining oral health as well as preventing and treating periodontal diseases are emphasized. At the same time, this may provide novel approaches to study the relationship between periodontal diseases and neurological disorders in the prevention and treatment strategies of neurological disorders.
Alzheimer Disease ; Depressive Disorder, Major/complications* ; Humans ; Inflammation/complications* ; Periodontal Diseases/complications* ; Periodontium

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-β (Aβ) pathologies in the hippocampus, and supplementation with folate and vitamin B12 (FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for 14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Aβ and tau pathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Aβ accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein (APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.
Alzheimer Disease ; etiology ; metabolism ; pathology ; therapy ; Amyloid beta-Peptides ; metabolism ; Animals ; Dietary Supplements ; Disease Models, Animal ; Folic Acid ; therapeutic use ; Homocysteine ; Hyperhomocysteinemia ; complications ; metabolism ; pathology ; therapy ; Male ; Rats, Sprague-Dawley ; Retina ; metabolism ; pathology ; Retinal Vessels ; metabolism ; pathology ; Vitamin B 12 ; therapeutic use ; tau Proteins ; metabolism

BACKGROUND: To investigate whether diabetes contributes to mortality for major types of diseases. METHODS: Six National Health and Nutrition Examination Survey data cycles (1999 to 2000, 2001 to 2002, 2003 to 2004, 2005 to 2006, 2007 to 2008, and 2009 to 2010) and their linked mortality files were used. A population of 15,513 participants was included according to the availability of diabetes and mortality status. RESULTS: Participants with diabetes tended to have higher all-cause mortality and mortality due to cardiovascular disease, cancer, chronic lower respiratory diseases, cerebrovascular disease, influenza and pneumonia, and kidney disease. Confounder-adjusted Cox proportional hazard models showed that both diagnosed diabetes category (yes or no) and diabetes status (diabetes, prediabetes, or no diabetes) were associated with all-cause mortality and with mortality due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease. No associations were found for cancer-, accidents-, or Alzheimer's disease-related mortality. CONCLUSION: The current study's findings provide epidemiological evidence that diagnosed diabetes at the baseline is associated with increased mortality risk due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease, but not with cancer or Alzheimer's disease.
Alzheimer Disease ; Cardiovascular Diseases ; Cerebrovascular Disorders ; Diabetes Complications ; Diabetes Mellitus ; Influenza, Human ; Kidney Diseases ; Mortality ; Nutrition Surveys ; Pneumonia ; Prediabetic State ; Proportional Hazards Models

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical characteristics of animal models that could help to better understand molecular mechanisms underlying the increased risk of CVD and AD in patients with prediabetes or T2D.
Alzheimer Disease ; Amyloid ; Blood Vessels ; Cerebrovascular Disorders ; Dementia ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Humans ; Islet Amyloid Polypeptide ; Models, Animal ; Neurologic Manifestations ; Pathology ; Prediabetic State ; Rodentia

OBJECTIVETo research Angelica tenuissima Nakai (ATN) for use in novel Alzheimer's disease (AD) therapeutics.

METHODSThe effect of a 30% ethanol extract of ATN (KH032) on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of β-amyloid (Aβ) peptide (Aβ) was investigated. Male C57Bl/6 mice were randomly divided into 4 groups, 10 in each group. KH032-treated groups were administrated with a low or high dose of KH032 (50 and 200 mg/kg, respectively), intragastrically for 16 days; distilled water was applied in the sham and negative groups. Open fifield test, Y maze and Morris water maze test were used for behavior test and cognitive ability. In addition, the neuroprotective effects of KH032 in Aβ-infused mice on the histopathological markers [neuronspecific nuclear protein (NeuN), Aβ] of neurodegeneration were examined. The levels of glial fibrillary acidic protein (GFAP), NeuN, phosphorylation extracellular signal-regulated kinase (ERK)/ERK, brain-derived neurotrophic factor (BDNF), phosphorylation cAMP response element-binding (CREB)/CREB protein expression were measured by Western blot.

RESULTSKH032 treatment ameliorated cognitive impairments, reduced the overexpression of Aβ, and inhibited neuronal loss and neuroinflammatory response in the Aβ-infused mice. Moreover, KH032 treatment enhanced BDNF expression levels in the hippocampus. Finally, KH032 treatment increased phosphorylation of ERK1/2 and CREB, vital for ERK-CREB signaling.

CONCLUSIONSKH032 attenuated cognitive defificits in the Aβ-infused mice by increasing BDNF expression and ERK1/2 and CREB phosphorylation and inhibiting neuronal loss and neuroinflflammatory response, suggesting that KH032 has therapeutic potential in neurodegenerative disorders such as AD.

Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Amyloid beta-Peptides ; Angelica ; chemistry ; Animals ; Brain ; pathology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cognitive Dysfunction ; complications ; drug therapy ; physiopathology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Male ; Maze Learning ; drug effects ; Memory, Short-Term ; drug effects ; Mice, Inbred C57BL ; Neurogenesis ; drug effects ; Neuroglia ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plaque, Amyloid ; drug therapy ; pathology ; physiopathology ; Signal Transduction ; drug effects

Alzheimer Disease ; complications ; pathology ; therapy ; Amyloid beta-Peptides ; metabolism ; Humans ; Mitochondria ; physiology ; Mitochondrial Diseases ; etiology ; tau Proteins ; metabolism