scholarly journals Management of the predementia stage of Alzheimer’s disease, complicated with hypoactive delirium

2021 ◽  
Vol 25 (6) ◽  
pp. 40-46
Author(s):  
O. N. Tkacheva ◽  
M. A. Cherdak ◽  
E. A. Mkhitaryan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Clinical Laboratory ◽  
Neurodegenerative Disorder ◽  
Cognitive Status ◽  
New Drugs ◽  
Antidementia Drugs ◽  
Diagnostic Approaches ◽  
Hypoactive Delirium

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in elderly population leading to the development of dementia. The emergence of modern diagnostic approaches makes possible reveal AD at predementia stage and study new drugs with pathogenetic and neuroprotective properties before severe cognitive impairment (dementia) arises. We present a description of patient with amnestic type of mild cognitive impairment with subsequent follow-up for more than two years. AD presence in mentioned patient was confirmed by evaluation of specific clinical, laboratory and instrumental biomarkers. Therapy with akatinol memantine (one of the main antidementia drugs in AD) at dose 20 mg/day was accompanied by cognitive defect stabilization. After two years of therapy acute severe decompensation related to hypoactive delirium due to respiratory infection was observed, which was followed by marked cognitive status deterioration. Daily dose of akatinol memantine was increased to 30 mg with subsequent restoration of baseline cognitive status. Possible mechanisms of akatinol memantine action and its effects in management of geriatric patients with AD including role in delirium therapy are discussed.

scholarly journals Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction

2021 ◽  
pp. 1-16
Author(s):  
Wei Wei ◽  
Yinghua Liu ◽  
Chunling Dai ◽  
Narjes Baazaoui ◽  
Yunn-Chyn Tung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Early Development ◽  
Neurodegenerative Disorder ◽  
Synaptic Dysfunction ◽  
Early Postnatal Development ◽  
Wild Type Female

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction. Objective: To explore strategies for early intervention to prevent Alzheimer’s disease. Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated. Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice. Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

scholarly journals A comparison of resting state EEG and structural MRI for classifying Alzheimer’s disease and mild cognitive impairment

2019 ◽  
Author(s):  
FR Farina ◽  
DD Emek-Savaş ◽  
L Rueda-Delgado ◽  
R Boyle ◽  
H Kiiski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Resting State ◽  
Healthy Aging ◽  
Neurodegenerative Disorder ◽  
Low Cost ◽  
Structural Mri ◽  
Lower Accuracy

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterised by severe cognitive decline and loss of autonomy. AD is the leading cause of dementia. AD is preceded by mild cognitive impairment (MCI). By 2050, 68% of new dementia cases will occur in low- and middle-income countries. In the absence of objective biomarkers, psychological assessments are typically used to diagnose MCI and AD. However, these require specialist training and rely on subjective judgements. The need for low-cost, accessible and objective tools to aid AD and MCI diagnosis is therefore crucial. Electroencephalography (EEG) has potential as one such tool: it is relatively inexpensive (cf. magnetic resonance imaging; MRI) and is portable. In this study, we collected resting state EEG, structural MRI and rich neuropsychological data from older adults (55+ years) with AD, with MCI and from healthy controls (n~60 per group). Our goal was to evaluate the utility of EEG, relative to MRI, for the classification of MCI and AD. We also assessed the performance of combined EEG and behavioural (Mini-Mental State Examination; MMSE) and structural MRI classification models. Resting state EEG classified AD and HC participants with moderate accuracy (AROC=0.76), with lower accuracy when distinguishing MCI from HC participants (AROC=0.67). The addition of EEG data to MMSE scores had no additional value compared to MMSE alone. Structural MRI out-performed EEG (AD vs HC, AD vs MCI: AROCs=1.00; HC vs MCI: AROC=0.73). Resting state EEG does not appear to be a suitable tool for classifying AD. However, EEG classification accuracy was comparable to structural MRI when distinguishing MCI from healthy aging, although neither were sufficiently accurate to have clinical utility. This is the first direct comparison of EEG and MRI as classification tools in AD and MCI participants.

scholarly journals YKL-40 as a Potential Biomarker for the Differential Diagnosis of Alzheimer’s Disease

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 60
Author(s):  
Ioannis Mavroudis ◽  
Rumana Chowdhury ◽  
Foivos Petridis ◽  
Eleni Karantali ◽  
Symela Chatzikonstantinou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Cochrane Library ◽  
Potential Biomarker ◽  
The Cochrane Library

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, associated with extensive neuronal loss, dendritic and synaptic changes resulting in significant cognitive impairment. An increased number of studies have given rise to the neuroinflammatory hypothesis in AD. It is widely accepted that AD brains show chronic inflammation, probably triggered by the presence of insoluble amyloid beta deposits and neurofibrillary tangles (NFT) and is also related to the activation of neuronal death cascade. In the present study we aimed to investigate the role of YKL-40 levels in the cerebrospinal fluid (CSF) in the diagnosis of AD, and to discuss whether there are further potential roles of this protein in the management and treatment of AD. We conducted an online search on PubMed, Web of Science, and the Cochrane library databases from 1990 to 2021. The quantitative analysis showed that the levels of YKL-40 were significantly higher in Alzheimer’s disease compared to controls, to mild cognitive impairment (MCI) AD (MCI-AD) and to stable MCI. They were also increased in MCI-AD compared to stable MCI. The present study shows that the CSF levels of YKL-40 could be potentially used as a biomarker for the prognosis of mild cognitive impairment and the likelihood of progression to AD, as well as for the differential diagnosis between AD and MCI.

scholarly journals Naturally Inspired Pyrimidines Analogues for Alzheimer’s Disease

2020 ◽  
Vol 19 (2) ◽  
pp. 136-151
Author(s):  
Shivani Singh ◽  
Meenakshi Dhanawat ◽  
Sumeet Gupta ◽  
Deepak Kumar ◽  
Saloni Kakkar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Multicomponent Reactions ◽  
Neurodegenerative Disorder ◽  
The Body ◽  
New Drugs ◽  
Atom Economy ◽  
Step Process ◽  
One Step ◽  
Made In

: Alzheimer’s disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.

scholarly journals Treatment of canine cognitive dysfunction with novel butyrylcholinesterase inhibitor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maja Zakošek Pipan ◽  
Sonja Prpar Mihevc ◽  
Malan Štrbenc ◽  
Urban Košak ◽  
Ilija German Ilić ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Cognitive Abilities ◽  
Cognitive Status ◽  
Moderate Cognitive Impairment ◽  
Interesting Candidate ◽  
Butyrylcholinesterase Inhibitor

AbstractCanine cognitive dysfunction (CCD) is common in aged dogs and has many similarities with Alzheimer’s disease. Unfortunately, like Alzheimer’s disease, CCD cannot be cured. In the present study, we treated dogs with CCD with our newly developed and characterized butyrylcholinesterase inhibitor (BChEi). Seventeen dogs were randomized into two groups (treated with BChEi and untreated) and followed for 6 months at regular check-ups. The dogs’ cognitive status was determined by a Canine Dementia Scale (CADES) questionnaire and two cognitive tests. In dogs with moderate cognitive impairment, treatment caused significant improvement in the clinical rating of cognitive abilities and the performance-based tests of cognitive functioning when compared to the untreated group (p < 0.001). Dogs treated with BChEi showed markedly improved cognitive function with enhanced quality of life. No side effects were observed in the treated dogs with moderate cognitive impairment. According to the results of this preliminary study, there is an indication that novel BChEi may be a promising drug for the treatment of CCD in dogs and may be an interesting candidate for the treatment of Alzheimer's disease in humans. However, further clinical studies are needed to confirm this.

scholarly journals Drug Repurposing for Alzheimer’s Disease based on Protein-Protein Interaction Network

2021 ◽  
Author(s):  
Negar Sadat Soleimani Zakeri ◽  
Saeid Pashazadeh ◽  
Habib MotieGhader
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Neurodegenerative Disorder ◽  
Gentian Violet ◽  
Interaction Network ◽  
New Drugs ◽  
Bipartite Network ◽  
Medical Studies ◽  
Gene Complexes

Abstract Background: Alzheimer's disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment is vital. This study proposes a method to extract substantial gene complexes and accomplish an enrichment analysis to introduce the most significant biological procedures. The next step is extracting the drugs related to AD and introduce some new drugs which may be useful for this disease. Results: To this end, protein-protein interactions (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. The next step was to construct a five bipartite network representing the genes of each group and their target miRNAs. Finally, a complete network including all the genes related to each gene complex group and genes’ target drug was illustrated. medical studies and publications were analyzed thoroughly to introduce AD-related drugs. Conclusions: This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. RALOXIFENE, GENTIAN VIOLET are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. These two drugs.

scholarly journals Prospective predictors of decline v. stability in mild cognitive impairment with Lewy bodies or Alzheimer's disease

2020 ◽  
pp. 1-9
Author(s):  
Calum A. Hamilton ◽  
Fiona E. Matthews ◽  
Paul C. Donaghy ◽  
John-Paul Taylor ◽  
John T. O'Brien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Latent Class ◽  
Lewy Bodies ◽  
Cognitive Status ◽  
Rapid Decline ◽  
Visual Hallucinations ◽  
Full Cohort

Abstract Background Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD). Methods A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function. Results Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline. Conclusions These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.

Blink rate study in patients with Alzheimer's disease, Mild Cognitive Impairment and Subjective Cognitive Decline

2021 ◽  
Vol 19 ◽  
Author(s):  
Fabrizia D’Antonio ◽  
Maria Ilenia De Bartolo ◽  
Gina Ferrazzano ◽  
Micaela Sepe Monti ◽  
Letizia Imbriano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Status ◽  
Subjective Cognitive Decline ◽  
Blink Rate ◽  
Compensatory Mechanisms ◽  
Rate Study

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p<0.001), whereas AD subjects had a lower BR than HCs (p<0.05). Conversely, SCD subjects had a BR similar to HCs. No significant correlations emerged between neuropsychological scores and BR in SCD, MCI, and AD subjects. Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

Abstract MP18: Covid-19 Susceptibility and Mortality Among Individuals With Mild Cognitive Impairment, Alzheimer’s Disease and Related Dementias

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Alan Pan ◽  
Jennifer Meeks ◽  
Thomas Potter ◽  
Osman Khan ◽  
Sudha Seshadri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Laboratory ◽  
Management Strategies ◽  
High Risk Group ◽  
Targeted Prevention ◽  
Logistic Regression Models ◽  
Comorbidity Burden

Introduction: We evaluated the burden of SARS-CoV-2 susceptibility and COVID-19 mortality associated with Mild Cognitive Impairment (MCI) or Dementia (MCID). Methods: We analyzed data from COVID-19 Outcomes Registry (CURATOR) at Houston Methodist; a tertiary healthcare system in greater Houston. All adult (≥ 18 years) patients tested for SARS-CoV-2 RNA in nasopharyngeal swabs were included. Utilizing validated ICD-10 codes (MCI, Alzheimer’s Disease, Vascular and Other Dementias) and use of MCID specific medications, we flagged patients with preexisting MCID. Logistic regression models were fitted to evaluate the odds of SARS-CoV-2 susceptibility and COVID-19 mortality associated with preexisting MCID. Odds ratios (OR) and 95% Confidence Intervals (CI) are reported. Results: Between March 3 and August 10, 2020; 86,614 individuals were tested, of whom 14,233 (16.4%) tested positive, with 4,473 (31.4%) hospitalizations, and 431 (9.6%) deaths. Overall 3,069 individuals had preexisting MCID; among whom 518 (16.9%) tested positive. Among all SARS-CoV-2 positive cases, MCID patients (vs. non MCID group) were older (79.9 vs. 47.3 years) and had higher overall comorbidity burden (median Charlson Comorbidity Index: 6 vs. 0), with higher proportion (%) of hypertension (90.3 vs. 39.0), heart failure (37.8 vs. 7.5), diabetes (69.3 vs. 28.2), and cancer (14.5 vs. 4.8). Mortality among MCID patients (vs. non MCID) was 22.3% vs. 8.6%. In fully adjusted models (demographics, comorbidities, clinical / laboratory parameters, complications, treatment and ICU admission), pre-existing MCID was independently associated with higher SARS-CoV-2 susceptibility, OR (CI) 1.62 (1.46-1.80) and in-hospital mortality OR (CI): 1.79 (1.23-2.61) among COVID-19 patients (graphic). Conclusions: Regardless of age, MCID is a potential risk factor for SARS-CoV-2 infection and COVID-19 mortality. Targeted prevention and management strategies are warranted for this high-risk group.

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