Dementia in old age: from diagnosis to fatal outcome

Background: It is well known, that old age dementias steadily grow progressively worse and inevitably lead to fatal outcome. Mortality indices in foreign research largely vary, they are practically absent in domestic scientific studies, and official statistical data on the prevalence of dementia and the cause of death do not reflect the real situation. The Objective of the study was to perform the analysis of completed cases of late age dementias from the materials of observations in Alzheimer’s disease center of the Mental Health Research Center.Patients and Methods: Observational study, using prospective method of out-patient observation of subjects with dementias, who consulted Alzheimer’s disease center in 2007-2016 for the first time, made it possible to obtain reliable data on 217 patients, who died during this period.Results: More than one third of such cases (39%) referred to nosologically various dementias with an early onset of the disease. In more than half of the cases (58%) the cause of death was medical pathology. In the rest of the patients severe or terminal stage of the basic disease was noticed toward the end of life under conditions of home care.Conclusions: Holistic view of the clinical picture of old age dementias (from the onset of the disease till the fatal outcome) is necessary for creation of incidence registers and obtaining of science-based statistical indices of survival, mortality and causes of death. It is necessary to develop measures of assistance to families of patients with the most severe stage of dementias, creation of out-patient and in-patient network of hospices for this contingent of patients.

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Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9096409 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Sirui Guo ◽

Jiahong Wang ◽

Huarong Xu ◽

Weiwei Rong ◽

Cheng Gao ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pc12 Cells ◽

Protein Signaling ◽

Pi3k Inhibitor Ly294002 ◽

Single Target ◽

Biological Methods ◽

Cognition Impairment ◽

First Time

Alzheimer’s disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aβ25-35 and D-gal-induced AD rats and Aβ25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aβ25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

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Spared and Impaired Abilities in Community-Dwelling Patients Entering the Severe Stage of Alzheimer’s Disease

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000255635 ◽

2009 ◽

Vol 28 (5) ◽

pp. 427-432 ◽

Cited By ~ 24

Author(s):

Anne-Sophie Gillioz ◽

Hélène Villars ◽

Thierry Voisin ◽

Frédéric Cortes ◽

Sophie Gillette-Guyonnet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Community Dwelling ◽

Severe Stage

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TMCC2 Associates with Alzheimer's Disease Pathology

10.1101/2021.08.14.456332 ◽

2021 ◽

Author(s):

Paul C R Hopkins ◽

Claire Troakes ◽

Guy Tear

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apoe Genotype ◽

Coiled Coil ◽

Amyloid Protein ◽

Neuritic Plaques ◽

Protein Precursor ◽

Apoe Isoforms ◽

First Time ◽

Differential Affinity

We previously identified Transmembrane and Coiled-Coil 2 (TMCC2) as a protein that forms complexes with both apolipoprotein E (apoE) and the amyloid protein precursor (APP) and which displayed differential affinity for apoE isoforms apoE3 and apoE4. Here we have for the first time examined TMCC2 in the human brain and found that it is affected by APOE genotype and brain region. We further observed that TMCC2 associates with the pathology of Alzheimer's disease in dense core and neuritic plaques. TMCC2 is therefore positioned to mediate impacts of apoE4 on Alzheimer's disease pathology.

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Factors underlying cognitive decline in old age and Alzheimer’s disease: the role of the hippocampus

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0086 ◽

2017 ◽

Vol 28 (7) ◽

pp. 705-714 ◽

Cited By ~ 20

Author(s):

Wafa Jaroudi ◽

Julia Garami ◽

Sandra Garrido ◽

Michael Hornberger ◽

Szabolcs Keri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Personality Traits ◽

Old Age ◽

Brain Regions ◽

Personality Factors ◽

Associated Symptoms ◽

Lifestyle Patterns

AbstractThere are many factors that strongly influence the aetiology, development, and progression of cognitive decline in old age, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). These factors include not only different personality traits and moods but also lifestyle patterns (e.g. exercise and diet) and awareness levels that lead to cognitive decline in old age. In this review, we discuss how personality traits, mood states, and lifestyle impact brain and behaviour in older adults. Specifically, our review shows that these lifestyle and personality factors affect several brain regions, including the hippocampus, a region key for memory that is affected by cognitive decline in old age as well as AD. Accordingly, appropriate recommendations are presented in this review to assist individuals in decreasing chances of MCI, dementia, AD, and associated symptoms.

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tRNA-Derived Fragments in Alzheimer’s Disease: Implications for New Disease Biomarkers and Neuropathological Mechanisms

Journal of Alzheimer s Disease ◽

10.3233/jad-200917 ◽

2020 ◽

pp. 1-14

Author(s):

Wenzhe Wu ◽

Inhan Lee ◽

Heidi Spratt ◽

Xiang Fang ◽

Xiaoyong Bao

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurological Diseases ◽

Disease Stage ◽

Expression Change ◽

Disease Biomarkers ◽

Qrt Pcr ◽

Rna Fragments ◽

First Time ◽

Polyadenylation Factor

Background: Alzheimer’s disease (AD) is the most common type of dementia caused by irreversible neurodegeneration, with the onset mechanisms elusive. tRNA-derived RNA fragments (tRFs), a recently discovered family of small non-coding RNAs (sncRNAs), have been found to associate with many human diseases, including infectious, metabolic, and neurological diseases. However, whether tRFs play a role in human AD development is not known. Objective: This study aimed to explore whether tRFs are involved in human AD. Methods: Thirty-four postmortem human hippocampus samples were used. The expression of Drosha, Dicer, and angiogenin (ANG), three ribonucleases responsible for the biogenesis of sncRNAs, was determined by qRT-PCR and western blot. The tRFs in the hippocampus was detected by qRT-PCR or northern blot. We also used qRT-PCR to quantify NOP2/Sun RNA methyltransferase 2 (NSun2) and polyadenylation factor I subunit 1 (CLP1), two tRNA modification enzymes. Results: tRFs derived from a subset of tRNAs are significantly altered in the hippocampus of AD patients. The expression change of some tRFs showed age- and disease stage-dependent. ANG is significantly enhanced in AD, suggesting its role in inducing tRFs in AD. The expression of NSun2 in AD patients younger than 65 was significantly decreased. According to a previous report supporting NSun2-mediated tRNA methylation modification making tRNA less susceptible to ANG-mediated cleavage, our results suggested that the decrease in NSun2 may make tRNAs less methylated and subsequently enhanced tRF production from ANG-mediated tRNA cleavage. Conclusion: Our studies demonstrated for the first time the involvement of tRFs in human AD.

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