Alzheimer's Disease

CONTEXT:
Depression is common in dementia, especially in the early stages, with important clinical implications, but the etiology is unknown and most likely heterogeneous. Antidepressant use in the elderly without dementia has previously been shown to be associated with high risks of adverse events and with structural brain alterations.

OBJECTIVE:
To investigate cortical changes associated with depression and antidepressant use in patients with mild Alzheimer's disease (AD) and Lewy body dementia (LBD).

METHODS:
74 subjects with mild AD and LBD from geriatric and psychiatry outpatient clinics in Western Norway were included. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depression. Automatic preprocessing using Freesurfer included steps for white and grey matter surface reconstruction. The resulting cortical thickness was analyzed using linear modeling.

RESULTS:
Clusters of depression-associated thinning were found in prefrontal and temporal areas. Treatment-associated thinning was observed in the parahippocampal region and was significant even after correction for age, sex, AD/LBD diagnosis, and MADRS scores.

CONCLUSION:
Depression in mild AD and LBD is associated with cortical thinning in prefrontal and temporal areas. The findings suggest that depressive symptoms in mild dementia could develop due to neurodegeneration in the same neural circuits that are critical for depression across different brain disorders. Antidepressant use in patients with mild AD and LBD is associated with parahippocampal thinning. Taken together with low efficacy of antidepressants in cognitively impaired patients and high risks of adverse events, our results suggest a need to re-evaluate the treatment approaches for depression and the role of antidepressants in patients with dementia.

The objective of this investigation done in the Neuropsychological Section of the Hospital Universitario de Caracas was to identify the main indicators in a battery of neuropsychological tests that permit to predict the evolution to Dementia of the Alzheimer´s Type (DTA) in patients previously diagnosed with Mild Cognitive Impairment (MCI). Through a non probabilistic sampling we got a sample of 30 patients from both gender, 46 to 81 years old, whose evolution was evaluated generating two diagnostic groups: DTA and MCI. The results were analized with U-Mann Whitney’s coefficient; we found that the Rey’s Audioverbal Learning Test intent VII, index V-VII, I-VI and errors in R were the ones who could discriminate both groups.

Project EAR (Environments for Alzheimer’s-friendly Radio) involves working alongside BBC Radio Devon to make the mechanics of radio-broadcasting more dementia friendly. The initial feedback stage was conducted using small sample discussions. There was no standardized questionnaire used, but the general question of “how can we make radio more dementia friendly” was put to people, including some of the answers already provided to give people a starting point for discussions. This information was used to structure the fully-produced 60 minute broadcast on  BBC Radio Devon “Music, Memory and Making Radio”. The documentary structure was an unusual mix of music and speaking, with multiple repetitions of the presenters’ names. The topic of the programme was repeatedly explained, mini-features kept as short as possible, and during the recording of interviews, signs were put up asking people to speak clearly. Mini-features included: what makes music memorable, how music can be used to help people with dementias, and initial considerations regarding dementia-friendly radio broadcasts. Below is an overview of the making of the programme; as well as samples of feedback we have been receiving from broadcasters, people living with dementia and their carers.

WCY Leung, YF Shea, SC Lee, LW Chu
Psychogeriatrics. 2019 Feb 27
doi :  10.1111/psyg.12432

Hyperphagia is characterized by increased food intake, active searching for food in between meals, and loss of satiety. 1-3 It has been observed in patients with impaired cognitive function. In this case series, we describe four patients with Alzheimer's disease (AD) who presented at our clinic with disturbing eating behaviour. A 91-year-old man was admitted after having a poor appetite for 2 weeks. He was known to have diabetes mellitus type 2 and had recently been prescribed gliclazide and metformin. He also presented with a 6-month history of anterograde episodic memory impairment with apraxia, temporal and spatial disorientation, and an inability to bathe. There was no clinical evidence of depression. Physical examination was unremarkable. Thyroid function test, vitamin B 12 level, and folate level were within normal range. Brain computed tomog-raphy showed bilateral medial temporal lobe atrophy. He was clinically diagnosed with AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association diagnostic criteria. Neither an active infection nor another identifiable secondary cause was found to have caused the patient's lack of appetite. Met-formin was stopped in view of the limited oral intake. Off-label use of oral megestrol acetate 40 mg twice daily was started, and the patient was discharged with marked improvement of appetite. The patient was admitted for one week. However, he was readmitted with hyperphagia 2 weeks after discharge. His relatives noted an absence of sati-ety, with frequent inappropriate requests for food. He was found searching for food in the kitchen late at night and, on a few occasions, had consumed his dog's canned food. In the absence of any organic causes based on clinical examination and laboratory tests, megestrol acetate was stopped. Hyperphagia gradually subsided a few days later. At our follow-up clinic 8 weeks later, there was no evidence of hyperphagia. Our encounter with the first patient prompted us to review the case records of 94 AD patients (14 with cerebrospinal biomarkers support, 4 80 with 18 F-fluorodeoxyglucose-positron emission tomog-raphy support, and 18 with amyloid load confirmed on 11 C-Pittsburgh compound B positron emission tomography). From these 94 cases, we identified three more AD patients with hyperphagia (Table 1, Appendix S1), meaning the prevalence of hyper-phagia was 4.2% (4/95). There was a predominance of male patients (75%). Hyperphagia developed between 2 weeks and 5 years after the diagnosis of AD and lasted transiently for 2 weeks to 5 months. All cases resulted in an increase in bodyweight. The relatives of these three patients were taught behavioural management techniques, including keeping food out of sight, using distraction techniques, and eating low-calorie snacks. One patient was managed by stopping the causa-tive medication. To the best of our knowledge, medication has not been previously regarded as a potential cause of hyperphagia, and there have been no reported cases of hyperphagia due to the administration of meges-trol. Megestrol is a progestin with anti-androgen activity that is marketed for use as an appetite stimulant in patients with cancer-related cachexia. Occasionally , it has been used off-label in elderly patients with poor appetite due to various causes. Our case demonstrated the drastic effect of megestrol on appetite stimulation, to the extent of hyperphagia or even pica. Previously, 5-hydroxytryptamine receptor 4 was reported to mediate anorexia. 5 Decreased 5-hydroxytryptamine receptor 4 density in the temporal cortex was associated with a higher incidence of hyperphagia in patients with AD. 5 Our case series further suggested that hyperphagia in AD is mostly a transient problem that lasts for months. The

We studied a novel function of the presenilins (PS1 and PS2) in governing capacitative calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores. Abrogation of functional PS1, by either knocking out PS1 or expressing inactive PS1, markedly potentiated CCE, suggesting a role for PS1 in the modulation of CCE. In contrast, familial Alzheimer's disease (FAD)-linked mutant PS1 or PS2 significantly attenuated CCE and store depletion-activated currents. While inhibition of CCE selectively increased the amyloidogenic amyloid beta peptide (Abeta42), increased accumulation of the peptide had no effect on CCE. Thus, reduced CCE is most likely an early cellular event leading to increased Abeta42 generation associated with FAD mutant presenilins. Our data indicate that the CCE pathway is a novel therapeutic target for Alzheimer's disease.

In the course of Alzheimer’s disease (AD), early pathological changes in the brain start decades before any clinical
manifestation. The concentration levels of AD cerebrospinal fluid (CSF) biomarkers, such as amyloid-1-42 (A1-42), total
tau (T-tau), and phosphorylated tau (P-tau), may reflect a cerebral pathology facilitating an early diagnosis of the disease and
predicting a cognitive deterioration. The aim of this study was to estimate the prevalence of AD CSF biomarkers in those
individuals with a subjective cognitive decline (SCD), a mild cognitive impairment (MCI), and Alzheimer’s dementia (AD-D),
together with the relationships between the biomarkers, an APOE 4 presence, and a verbal episodic memory performance.
We included 252 patients from the memory clinic with a diagnosis of SCD (n = 85), MCI (n = 87), and AD-D (n = 80). A
verbal episodic memory performance level was assessed and was based on a delayed recall trial from the 10-word list of an
auditory verbal learning task (AVLT). We found that the patients with more severe cognitive impairments had significantly
lower levels of A1-42 and higher levels of T-tau and P-tau. This pattern was also typical for the APOE 4 carriers, who had
lower levels of A1-42 than the noncarriers in the AD-D and MCI groups. The levels of T-tau and P-tau were significantly
higher in the APOE 4 carriers than in the noncarriers, but only in the MCI patients. The AVLT performance in the whole
study samples was predicted by age, A1-42, and the T-tau CSF biomarkers, but not by the APOE genotyping.

Alzheimer’s disease is one of the most severe types of dementia that causes problems with memory, thinking, and behavior. Biotechnology and bioinformatics are nowadays involved in the establishment of advanced methods of diagnosis and treatment, including molecular medicine, personalized medicine, gene identification and manipulation, as well as neural engineering. Next-generation sequencing is one of the strongest tools for studying genetic diseases and gene mutations. Additionally, brain-computer interface could be used in the near future to assist people with paralysis or other related disorders and physical injuries to move toward into a better way of life, restoring memory or improving the way of everyday life. This chapter aims to provide an overview of the most common and an advanced application of biotechnology and bioinformatics in Alzheimer’s including the genomewide association studies and the role of microbiome detection in Alzheimer’s disease.

Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease. Recent studies suggest that amyloid-beta (Aβ) deposit can be detected several years after TBI. However, it is unknown whether post-TBI Aβ deposits arise from short-term changes in Aβ metabolism or reflect a long-term sequela. To answer this question, we evaluated the cerebrospinal levels of Aβ several months after a severe TBI. The participants of this study were eight consecutive patients who developed a disorder of consciousness after a TBI, including seven in a minimally conscious state and one with unresponsive wakefulness syndrome (mean age: 35.4 ± 14.2 years, mean time since brain injury 297.9 ± 189.8 days). Cerebrospinal Aβ 1-42 peptide was measured using a commercially available Aβ enzyme-linked immunoassay kit. Reduced Aβ 1-42 levels were observed in seven of eight (87.5%) patients with severe post-TBI disorders of consciousness, with the magnitude of reduction among these seven patients ranging from 27 to 75.1% of the lower normal limit. These results point to prolonged changes in Aβ metabolism after a TBI and they suggest a potential mechanism of long-term neurotoxicity. NeuroReport 28:250-252

Background: It has been suggested that the ADAS-Cog is not uniformly sensitive to measuring cognitive decline in Alzheimer disease across mild and moderate patients. As a result, the NTB (neuropsychological test battery) was introduced as an alternative which measures cognitive de- cline in both mild and moderate patients equally well (Harrison et al, Arch Neurol 64:1323-9, 2007). Methods: The psychometric properties of NTB are examined in two randomized, double-blind trials; one 12-week placebo- and active-controlled (w 350 patients) and the other 24-week placebo-con- trolled (w 330). The test-retest reliability, ratio of within subject variability to between subject variability, and internal consistency of NTB in addition to correlation of NTB with other cognitive and functional measures are evaluated using data from the placebo patients. The sensitivities of NTB and ADAS-Cog are assessed as a function of baseline MMSE (Mini-Mental State Examination) scores using data from the active and the placebo arms. Results: It is confirmed that the NTB has good psychometric properties. Although the NTB and ADAS-Cog are equally sensitive in detecting change in the overall population, differences are observed when stratified by baseline MMSE scores. While the NTB is more sensitive than ADAS-Cog among the mild patients, the reverse is observed among the moderate patients. Conclusions: The NTB has good psychometric proper- ties. Based on two studies of relatively short duration, both the NTB and ADAS-Cog are shown to be good instruments for detecting drug effects on cognitive decline among AD patients. The sensitivity of these instruments needs to be evaluated in validation studies of longer duration.

If good Alzheimer's caregiving necessitates empathy, and plenty of it, love stretches it to its uttermost boundary.  By providing insights Into the struggles of Alzheimer's patients and caregivers, literature can increase our understanding, empathy, and love for all those fighting against it.,

The purpose of this brief note is to present a discussion of the first two sessions of a poetry group conducted with moderately to severely cognitively impaired adults in a nursing home. Exercises and techniques used with this population are discussed. Poetry groups such as this may provide joy those who suffer, a chance to re-experience memories, to connect to others, and the creation of moments of increased value and meaning.

Objectives: The incidence of metabolic syndrome (MetS) in menopausal women is one of the main health care concerns. MetS clusters are related to an imbalance in pro-and anti-inflammatory adipokines such as secreted frizzledÀrelated protein 5 (SFRP5) and wingless-type mammary tumor virus integration site family, member 5A (WNT5A). WNT5A induces an inflammatory state to induce insulin resistance and further patho-logic consequences. Recent strategies to prevent progression of MetS to diabetes have focused on conservative treatments such as exercise and herbal medicine. The aim of this study was to investigate the mechanistic effects of cotreatment with cinnamon extract and 12-wk high-intensity endurance training on MetS components considering the non-canonical WNT5A signaling. Method: Thirty-two female ovariectomized Wistar rats were divided into the following four groups (n = 8/ group): exercise (Ova+Exe), cinnamon extract (Ova+Cin), exercise with cinnamon extract (Ova+Exe+Cin) and saline (Ova+Sal). One group of rats undergoing surgery without removal of the ovaries was considered as a sham. After 3 mo of experimental intervention, waist circumference, serum concentrations of glucose, insulin , lipid profile, tumor necrosis factor-a, WNT5A, and SFRP5 were measured. Results: Data showed a significant reduction in serum glucose, low-density lipoprotein, homeostasis model assessment estimate of insulin resistance, and tumor necrosis factor-a, but an increase in SFRP5 level in Ova +Exe, Ova+Cin and Ova +Exe+Cin groups compared with Ova+Sal group (P < 0.05). Serum WNT5A significantly was reduced only in Ova+Exe+Cin group (P = 0.02). Conclusion: The present study indicated that high-endurance training combined with aqueous cinnamon extract supplementation for 12 wk more efficiently alleviated insulin resistance and metabolic dysfunctions via reduction in noncanonical WNT signaling in ovariectomized rats.

Global research in the field of pharmacology has not yet found effective drugs to treat Alzheimer's disease (AD). Thus, alternative therapeutic strategies are under investigation, such as neurostimulation by physical means. Radio electric asymmetric conveyer (REAC) is one of these technologies and has, until now, been used in clinical studies on several psychiatric and neurological disorders with encouraging results in the absence of side effects. Moreover, studies at the cellular level have shown that REAC technology, with the appropriate protocols, is able to induce neuronal differentiation both in murine embryonic cells and in human adult differentiated cells. Other studies have shown that REAC technology is able to positively influence senescence processes. Studies conducted on AD patients and in transgenic mouse models have shown promising results, suggesting REAC could be a useful therapy for certain components of AD.

Introduction: Epidemiological studies suggest convincing evidence for a meaningful relationship between type 2 diabetes and dementia. It also shows that type 2 diabetes is a major cause of Alzheimer's disease. Given the Iranian population's profile of about 31 million middle-aged people, in the next two decades, older people will form a large population. On the other hand, the increase in Alzheimer's in the elderly is due to the prevalence of this disorder and the adverse effects and adverse effects in the next two decades. And so far, quantitative research has been conducted to investigate the risk of Alzheimer's disease in diabetic patients in Khuzestan province. Therefore, this study titled "The communication Between Diabetes and Alzheimer's Disease: study on diabetic patients referring to health centers in three cities of Khuzestan province" was done.

Materials and Methods: This retrospective cross-sectional descriptive study was conducted on diabetic patients hospitalized in Shoushtar, Behbahan, and Abadan, between 2015 to 2017. The files of these patients who were diagnosed with diabetes and referred to medical centers in the mentioned cities that were extracted from medical records of city hospitals and entered the study. Data were then entered into SPSS software version 20. Data were analyzed using descriptive statistics, analytical tests and the significance level of P <0.05.

Results: In this study, the mean age of patients was 57.00 ± 46.23 years. A statistically significant relationship was found between diabetes and those with Alzheimer's disease (p = 0.006). However, there was no significant relationship between diabetes and those with a history of cardiovascular disease (p = 0.09). There was no significant relationship between education and those with Alzheimer's disease (0.06). But a statistically significant relationship was found between jobs with those with Alzheimer's disease (0.003).

Conclusion: In this study, there was a significant relationship between diabetes and those with Alzheimer's disease. Therefore, this study showed the risk of Alzheimer's disease in diabetic patients in the three mentioned cities. More epidemiological and clinical research is needed to investigate the relationship between these two diseases in a wider and larger volume.

O artigo dialoga com etnografias e estudos qualitativos sobre o fenômeno das demências. Dada a centralidade que o
termo doença de Alzheimer angariou nesse campo, retoma sua história, as contínuas e atuais controvérsias a respeito
da doença, bem como os tratamentos e modos de cuidar, estudar e se relacionar com pessoas com demência. O campo
das demências tem questionado conceitos e abordagens metodológicas das ciências sociais, e transformado modos de
cuidar, tratar e medicar a velhice ao redor do mundo, contudo ainda é pouco conhecido no Brasil e são raras as revisões
de literatura que sistematizem o que foi produzido e apontem agendas de pesquisa contemporâneas.

Maria Filomena Mónica, nascida em Lisboa, em 1943, socióloga, historiadora, jornalista e escritora, escreveu um ensaio intitulado “A Morte”, editado pela Fundação Francisco Manuel dos Santos em 2011. Neste ensaio, Mónica debate a questão do direito à morte e à eutanásia, ou “morte assistida” como lhe prefere chamar, quando as circunstâncias impedem que o indivíduo esteja na posse das suas faculdades intelectuais e autonomia física.

The literature on death expectation in ill old age is mostly medical. A social science standpoint (especially quantitative) is practically absent. However, whether families, social and healthcare services can anticipate, support and prepare for the deaths of ill old adults is not reducible to the biomedical paradigm. Yet it is critical for end of life care (EOLC) policy. This study's aim is to investigate relatives' perception of death as unexpected in relation to both disease-related and care-related factors. Using the English Longitudinal Study of Ageing End-of-life Interviews Wave 6 this paper draws on probit regression analysis of unexpected (vs. expected) death in ill adults aged 50+. Findings are interpreted considering the containment of sudden death and the trajectories of dying in ill old age. The latter display overall visible decline preceding death. On this basis, EOLC literature and policy evidence death's uncertain timing as much as death's certain emergence in the horizon of expectation. Therefore, unexpected death in ill old age was interpreted as a failure to acknowledge dying, rather than the impossibility of discerning its approach. Very old age, dementia diagnoses and supported care environments were found to shape unexpected death.

Context: Human life is contested with the emergence of new infectious diseases and antibiotic-resistant pathogens, cellular deterioration due to oxidative stress, and age-related neurodegenerative disorders.

Aims: To evaluate the antibacterial, antioxidant, and acetylcholinesterase inhibitory activities of crude extract from the endophytic fungus Fusarium sp. isolate OQ-Fus-2-F as a basis for medical application.

Methods: Fusarium sp. isolate OQ-Fus-2-F was isolated from the stem of Euphorbia sp. plant. It was identified morphologically and based on 18S rRNA gene partial sequence. The isolated was cultivated in a malt extract glucose medium. Cell filtrate was extracted with ethyl acetate, and the crude extract was dried in vacuum. The crude extract was assessed for its antimicrobial activity through agar diffusion and micro-broth dilution assays; antioxidant activity was measured using DPPH and ABTS methods, and the anticholinergic activity was evaluated in terms of inhibition in acetylcholinesterase (AChE) activity.

Results: Crude extract of Fusarium sp. isolate OQ-Fus-2-F was more potent in inhibiting the growth of B. subtilis with a MIC value of 125 µg/mL. Its antioxidant activity was highly detected in ABTS than DPPH assay with IC50 values 37.5 ± 3.5 µg/mL and 191.3 ± 17.6 µg/mL, respectively. Moreover, the extract inhibited the AChE activity with IC50 177.0 ± 13.7 µg/mL.

Conclusions: Crude extract of Fusarium sp. isolate OQ-Fus-2-F has potential biomedical applications as it contains secondary metabolites with antimicrobial, antioxidant, and neuroprotective activates.

This paper presents research that illustrates how design thought and action has contributed to the co-design and development of a mass-produced product with people living with dementia. The research, undertaken in collaboration with Alzheimer Scotland, has adopted a range of disruptive design interventions for breaking the cycle of well-formed opinions, strategies, mindsets, and ways-of-doing, that tend to remain unchallenged in the health and social care of people living with dementia. The research has resulted in a number of co-designed interventions that will help change the perception of dementia by showing that people living with dementia can offer much to UK society after diagnosis. Moreover, it is envisaged that the co-designed activities and interventions will help reconnect people recently diagnosed with dementia to help build their self-esteem, identity and dignity and help keep the person with dementia connected to their community, thus delaying the need for formal support and avoid the need for crisis responses. The paper reports on an initial intervention where the author worked collaboratively with over 130 people diagnosed with dementia across Scotland in the co-design and development of a new tartan. The paper concludes with a number of recommendations for researchers when co-designing with people living with dementia.

There are unexplained links between human exposure to aluminium and the incidence, progression and aetiology of Alzheimer's disease. The null hypothesis which underlies any link is that there would be no Alzheimer's disease in the effective absence of a body burden of aluminium. To test this the latter would have to be reduced to and retained at a level that was commensurate with an Alzheimer's disease-free population. In the absence of recent human interference in the biogeochemical cycle of aluminium the reaction of silicic acid with aluminium has acted as a geochemical control of the biological availability of aluminium. This same mechanism might now be applied to both the removal of aluminium from the body and the reduced entry of aluminium into the body while ensuring that essential metals, such as iron, are unaffected. Based upon the premise that urinary aluminium is the best non-invasive estimate of body burden of aluminium patients with Alzheimer's disease were asked to drink 1.5 L of a silicic acid-rich mineral water each day for five days and, by comparison of their urinary excretion of aluminium pre-and post this simple procedure, the influence upon their body burden of aluminium was determined. Drinking the mineral water increased significantly (P < 0.001) their urinary excretion of silicic acid (34.3 ± 15.2 to 55.7 ± 14.2 µmol/mmol creatinine) and concomitantly reduced significantly (P = 0.037) their urinary excretion of aluminium (86.0 ± 24.3 to 62.2 ± 23.2 nmol/mmol creatinine). The latter was achieved without any significant (P > 0.05) influence upon the urinary excretion of iron (20.7 ± 9.5 to 21.7 ± 13.8 nmol/mmol creatinine). The reduction in urinary aluminium supported the future longer-term use of silicic acid as non-invasive therapy for reducing the body burden of aluminium in Alzheimer's disease.

Aims and objective: While loss of insight of cognitive deficits is a common phenomenon in patients with Alzheimer’s disease (AD), there is a lack of consensus regarding the presence of impaired insight among patients with mild cognitive impairment (MCI). We aim to investigate the clinical, cognitive, and be- havioral associations of anosognosia in AD and MCI subjects.
Methods: A consecutive series of 87 subjects (30 healthy older patients, 21 MCI, and 36 AD) each ac- companied by a caregiver, underwent clinical assessment including the evaluation of insight using the Anosognosia Questionnaire for Dementia (AQD). We also separately assessed Intellectual Function (AQD-IF) and Behavior domains of the AQD scale. Regression models were subsequently used to inves- tigate associations of AQD scores with cognitive and other neuropsychiatric symptoms, including de- pression and apathy.
Results: Both AD and MCI groups demonstrated significant anosognosia compared with the healthy control group. In the AD group, 55.6% had “Mild Anosognosia,” and 27.8% had “Severe Anosognosia.” In the MCI group, 42.9% showed “Mild Anosognosia,” and 9.5% had “Severe Anosognosia.” Greater levels of AQD-Total and AQD-IF were associated with lower Mini-mental state examination and higher apathy scores in the AD group. In the MCI group, caregiver burden was significantly associated with AQD-Total (p = 0.016) and AQD-IF (p = 0.039).
Conclusion: The results indicated that anosognosia is common in both AD and MCI patients and asso- ciated with cognitive dysfunction and apathy in AD. The findings of this study warrant further research to delineate the mechanisms of anosognosia as it poses a challenge to treatment outcomes.

—Mathematical and computational modellings are the necessary tools for reviewing, analysing, and predicting processes and events in the wide spectrum range of scientific fields. Therefore, in a field as rapidly developing as neuroscience, the combination of these two modellings can have a significant role in helping to guide the direction the field takes. The paper combined mathematical and computational modelling to prove a weakness in a very precious model in neuroscience. This paper is intended to analyse all-or-none principle in Hodgkin-Huxley mathematical model. By implementation the computational model of Hodgkin-Huxley model and applying the concept of all-or-none principle, an investigation on this mathematical model has been performed. The results clearly showed that the mathematical model of Hodgkin-Huxley does not observe this fundamental law in neurophysiology to generating action potentials. This study shows that further mathematical studies on the Hodgkin-Huxley model are needed in order to create a model without this weakness.

Der vorliegende Beitrag zeichnet den Weg von der Re- zur Dekonstruktion von ‚Demenz'. Dabei werden zunächst die rekonstruktiven Verfahren der Objektiven Hermeneutik beschrieben, um im Anschluss daran die Rekonstruktion am Material exemplarisch vorstellen zu können. Hieran anknüpfend werden zentrale Ergebnisse aus der Studie „Kontexte des Lebens. Lebenssituation demenziell erkrankter Menschen im Heim“ (Trescher 2013) dargelegt und vor dem Hintergrund aktueller Entwicklungen aus dem Bereich der Demenzforschung diskutiert. Im Mittelpunkt steht dabei der Befund der Notwendigkeit der Dekonstruktion des gegenwärtig vorherrschenden, medizinisch geprägten Verständnisses von ‚Demenz‘. Der Beitrag kritisiert die bestehenden Betreuungs- und Versorgungsstrukturen, die an ebendiesem ausgerichtet bzw. aus diesem heraus entstanden sind. Das medizinische Leitbild, so eine Kernthese, führt zwangsläufig zu Demütigungen auf interaktiver, institutioneller sowie gesamtgesellschaftlicher Ebene und bedarf einer theoriegeleiteten Reformulierung. Der Autor verweist dabei auf bereits bestehende Dekonstruktionsdiskurse, wie etwa ‚Geschlecht' oder ‚Behinderung'. In diesem Zusammenhang wird ebenfalls kritisiert, dass sich die Sonderpädagogik (welche als ‚Leitwissenschaft' die Entmedikalisierung von (geistiger) Behinderung maßgeblich vorantrieb) der Demenzthematik nur sehr schleppend annimmt, kann sie doch auf theoretische Paradigmen und einen breiten Fundus an handlungsleitenden Praxiskonzepten zurückgreifen.

Summary The hypothesis as to whether a benign species of bacteria could kill a virulent kind has to this point been untested. Recently it was shown that in the macrophage, bacteriophages, when properly introduced through a nonvirulent
microbe, had a killing rate for virulent AIDS Mycobacterium tuberculosis and Mycobacterium avium far in excess of modern day antibiotics. The study in effect brought a natural phenomena, lysogeny, whereby one bacterial colony kills another thru phage weaponry, to bear in the conquest of hard-to-kill, antibiotic resistant pathogens. This killing occurred intracellularly, within the white blood cell using Mycobacterium smegmatis, a benign bacterial species found generally in smegma secretions from human genitalia as well as soil, dust and water, and first identified
in 1884. The subsequent treatment of M. avium-infected, as well as M. tuberculosis-infected RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4 resulted in a unexpectedly large time- and titer-dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fused with the M. avium vacuole in macrophages. These results suggested a potentially novel concept to kill intracellular pathogenic bacteria and warrant future
development.

Contemporary research into health treats diagnosis as a central step in illness management and trajectories. Most public health policies, especially in the case of Alzheimer’s disease, claim that the earlier a diagnosis is made, the better it is for patients and caregivers. Quantitative and qualitative analysis from our longitudinal interview study, conducted with 60 caregivers of persons diagnosed with dementia, shows that this usual model of diagnosis [symptoms → diagnosis → meaning and caregiving] should be nuanced. First, diagnosis does not follow increased symptoms, but occurs rather through a process involving the observability of patients’ troubles and their interpretation of said troubles as requiring medical assistance ‐the ‘trouble?observability?interpretation convergence.’ Second, diagnosis does not systematically trigger the mobilisation of a caregiving network: such mobilisation may follow the diagnosis, but it can also provoke it, temporarily prevent it, or have no immediate impact. These observations beg the question: To what extent does diagnosis matter? We conclude by questioning the centrality of diagnosis in the illness trajectories and its crucial role in the mobilisation of a caregiving network, that is often taken for granted, and propose to distinguish between ‘anticipation diagnosis’ and ‘emergency diagnosis’.

Aim

As the population ages, the problem of dementia increases and affects a growing number of people. People with mental illness are known to be stigmatised and this has been the subject of numerous studies. There have been contradictory studies assessing the stigma attached to dementia, and the majority focus on stigma at a social level and the public perception of people with dementia. There have been a number of projects that included a study group of people with dementia. However, to date, this topic has not been discussed in Poland. Hence, the aim of this paper is to carry out a literature review addressing this issue.

Perspective

The problem of stigma attached to dementia is particularly significant as it affects not only the subject, but also their family, friends and health professionals. As people with dementia develop cognitive impairment and lose their independence, stigmatisation leads to their social isolation, despite their need for care. Stigma has emotional, behavioural and social implications, including diminished self-esteem, a feeling of anxiety and the development of a sense of shame and a fear of the judgement of others. Family members also deal with the stigma, which manifests itself as embarrassment and anxiety and causes their circle of friends and acquaintances to decrease. Current studies show that professionals can also play a negative role in the process of labelling and stigmatisation of patients.

Conclusion

Stigma is a serious and common problem in dementia. It seems necessary to target this issue in research and social discourse.

Alzheimer’s disease(AD) is a neurological disease. It affects memory. The livelihood of the people that are
diagnosed with AD. In this paper, we have discussed various imaging modalities, feature selection and
extraction, segmentation and classification techniques.

It is a chronic neurodegenerative disease that usually starts slowly gets worse over time and become incurable and the valid grounds of Alzheimer's disease [1] are poorly understood. About 70 % of the risk is believed to be genetic with many genes usually involved. Other risk factors include a history of head injuries, depression, or hypertension. Affected people increasingly rely on others for assistance, often placing a burden on the caregiver; the pressures can include social, psychological, physical, and economic elements. Exercise programs are beneficial with respect to activities of daily living and can potentially improve outcomes. The cause for most Alzheimer's cases is still mostly unknown except for 1 % to 5 % of cases where genetic differences have been identified. Symptoms can be treated with medication, but there is no cure. People who engage in intellectual activities such as reading, playing board games, crossword puzzles, musical instruments or regular social interaction and physical activity are also connected with a reduced risk of Alzheimer's disease despite usage of medications. Treatment may involve medications that are thought to decrease the rate of decline. Majority of patients will receive neuroimaging (CT, MRI) as a part of the diagnostic work. Genetic tests may be supportive in diagnosis but further studies are needed to confirm their reliability. No diagnostic test is definitive for Alzheimer's disease.

A B S T R A C T Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive deterioration of cognitive functions. The pathological hallmarks are extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles of tau protein. The cognitive deficits seen are thought to be due to synaptic dysfunction and neurochemical deficiencies. Various neurochemical abnormalities have been observed during progressive ageing, and are linked to cognitive abnormalities as seen with the sporadic form of AD. Acetylcholinesterase inhibitors are one of the major therapeutic strategies used for the treatment of AD. During the last decade, various new therapeutic strategies have shown beneficial effects in preclinical studies and under clinical development for the treatment of AD. The present review is aimed at discussing the neurobiology of AD and association of neurochemical abnormalities associated with cognitive deterioration and new therapeutic strategies for the treatment of AD.