Care Of Alzheimer's Disease Patients Research Articles

Aptamer-Functionalized Carbon Nanotube Field-Effect Transistor Biosensors for Alzheimer's Disease Serum Biomarker Detection.

Blood-biomarker-based tests are highly important for the early clinical diagnosis of Alzheimer's disease (AD) and the treatment and care of AD patients, but the complex serum environment and extremely low abundance of AD blood protein biomarkers present challenges. Nanomaterials are promising for constructing highly sensitive transistor-based biosensors due to their small size. However, such biosensors are difficult to fabricate on a large scale and suffer from the lack of combined optimization of reproducibility and sensitivity in complex physiological fluids. In this work, field-effect transistor (FET) biosensors based on highly uniform semiconducting carbon nanotube (CNT) thin films are mass produced to achieve highly sensitive and selective detection of the AD core blood biomarkers of β-amyloid (Aβ). The combination of the mass-produced CNT FET sensors and oligonucleotide aptamers as efficient bioreceptors enables reliable and reproducible sub-femtomolar detection in full human serum for Aβ42 and Aβ40 peptides and has outperformed other methods reported to date. The adsorption of biological substrates to the sensor was significantly reduced by multiple blocking steps, resulting in selectivity ratios of up to 730% (Aβ40) and 800% (Aβ42). The aptamer-functionalized CNT FET biosensor exhibits a large dynamic range (>104), rapid response time (several minutes), and low variation (<10%) and can be delivered as a low-cost and rapid clinical detection technology for the early diagnosis and mass screening of AD. This platform will help bring complex laboratory-based and expensive diagnostic tools to the point of care.

Global Public Interest and Seasonal Variations in Alzheimer's Disease: Evidence From Google Trends.

Background: As the world's population ages, Alzheimer's disease (AD), a common neurodegenerative disease, is a major challenge to human health in the future. Understanding the information needs on AD of the global public can contribute to the prevention and control of AD. The purpose of this study was to explore global public interest and seasonal variations in AD using Google Trends (GT).Methods: GT was used to obtain relative search volume (RSV) of the keyword “Alzheimer's disease” in six English-speaking countries (Australia, New Zealand, the USA, the UK, Canada, and Ireland) and the world from January 2004 to December 2020. Cosinor analysis was applied to detect the seasonality of AD-related RSV. Time series plot was used to observe the trend of annual mean AD-related RSV. Globally, hot topics and top rising topics related to AD were also analyzed. In addition, we also explored the geographical distribution characteristics of AD-related RSV.Results: AD-related RSV declined steadily from January 2004 to December 2013 and rose steadily from January 2014 to December 2020. Search popularity of AD is low in the southern hemisphere, compared to the northern hemisphere. Cosinor analysis showed that there were significant seasonal variations in AD-related RSV in six English-speaking countries (all P < 0.05). Interestingly, regardless of the hemisphere, peaks were observed in the winter months and trough in the summer months. Topics related to the characteristics and etiology of AD, early onset AD, AD-related associations, care of AD patients, and diseases that can easily be confused with AD had received special attention.Conclusions: There is increasing global public interest for AD and a significant seasonal variation in AD. A better understanding of the seasonal variations and public interest of AD by governments, health workers and patients can contribute to the prevention, management, and treatment of AD.

White Matter Deterioration May Foreshadow Impairment of Emotional Valence Determination in Early-Stage Dementia of the Alzheimer Type.

In Alzheimer Disease (AD), non-verbal skills often remain intact for far longer than verbally mediated processes. Four (1 female, 3 males) participants with early-stage Clinically Diagnosed Dementia of the Alzheimer Type (CDDAT) and eight neurotypicals (NTs; 4 females, 4 males) completed the emotional valence determination test (EVDT) while undergoing BOLD functional magnetic resonance imaging (fMRI). We expected CDDAT participants to perform just as well as NTs on the EVDT, and to display increased activity within the bilateral amygdala and right anterior cingulate cortex (r-ACC). We hypothesized that such activity would reflect an increased reliance on these structures to compensate for on-going neuronal loss in frontoparietal regions due to the disease. We used diffusion tensor imaging (DTI) to determine if white matter (WM) damage had occurred in frontoparietal regions as well. CDDAT participants had similar behavioral performance and no differences were observed in brain activity or connectivity patterns within the amygdalae or r-ACC. Decreased fractional anisotropy (FA) values were noted, however, for the bilateral superior longitudinal fasciculi and posterior cingulate cortex (PCC). We interpret these findings to suggest that emotional valence determination and non-verbal skill sets are largely intact at this stage of the disease, but signs foreshadowing future decline were revealed by possible WM deterioration. Understanding how non-verbal skill sets are altered, while remaining largely intact, offers new insights into how non-verbal communication may be more successfully implemented in the care of AD patients and highlights the potential role of DTI as a presymptomatic biomarker.

Identification and characterization of Aβ peptide interactors in Alzheimer’s disease by structural approaches

Currently, there are very limited pharmaceutical interventions for Alzheimer’s disease (AD) to alleviate the amyloid burden implicated in the pathophysiology of the disease. Alzheimer’s disease is characterized immunohistologically by the accumulation of senile plaques in the brain with afflicted patients progressively losing short-term memory and, ultimately, cognition. Although significant improvements in clinical diagnosis and care for AD patients have been made, effective treatments for this devastating disease remain elusive. A key component of the amyloid burden of AD comes from accumulation of the amyloid-beta (Aβ) peptide which comes from processing of the amyloid precursor protein (APP) by enzymes termed secretases, leading to production of these toxic Aβ peptides of 40–42 amino acids. New therapeutic approaches for reducing Aβ are warranted after the most logical avenues of inhibiting secretase activity appear less than optimal in ameliorating the progression of AD.Novel therapeutics may be gleaned from proteomics biomarker initiatives to yield detailed molecular interactions of enzymes and their potential substrates. Explicating the APPome by deciphering protein complexes forming in cells is a complementary approach to unveil novel molecular interactions with the amyloidogenic peptide precursor to both understand the biology and develop potential upstream drug targets. Utilizing these strategies we have identified EC 3.4.24.15 (EP24.15), a zinc metalloprotease related to neprilysin (NEP), with the ability to catabolize Aβ 1–42 by examining first potential in silico docking and then verification by mass spectrometry. In addition, a hormone carrier protein, transthyreitin (TTR), was identified and with its abundance in cerebrospinal fluid (CSF), found to clear Aβ by inhibiting formation of oligomeric forms of Aβ peptide. The confluence of complementary strategies may allow new therapeutic avenues as well as biomarkers for AD that will aid in diagnosis, prognosis and treatment.

COGNOS

Care plans are intended to improve the independence and functioning of patients with cognitive dysfunction and support the caregivers involved. They are an integral part of the Belgian reimbursement procedure for cholinesterase inhibitors. This nationwide, multicenter, observational study examined the content and implementation of the care plan along with patient satisfaction in community-dwelling patients newly diagnosed with Alzheimer disease in Belgium. The patients' opinion of their quality of life was measured using Anamnestic Comparative Self-Assessment (ACSA) scale. A total of 720 participants (453 female) were enrolled with 86.0% (619/719) living at home alone or with their spouse/partner. Cognitive problems (627/717, 87.4%) were the main reason for initiation of the consultation. Most patients had a caregiver (646/719, 89.8%): generally the spouse/partner (351/646, 54.3%) or a child (232/646, 35.9%). A total of 511 patients (71.0%) were prescribed a cholinesterase inhibitor after the initial consultation. A total of 236 care plans were advised with 169 (71.6%) realized and 157 of these (92.9%) considered adequate. Most patients were satisfied with the help received in the care plan (service satisfaction range, 80.0% to 98.6% of patients). Quality of life as rated by the patient significantly increased between baseline (average ACSA score: 5.2±2.4) and follow-up (5.8±2.1). The use of care plans appears to improve management of care for Alzheimer disease patients.

Aspects of awareness in patients with Alzheimer's disease

The purpose of the present study was to gain insight into Alzheimer's disease (AD) patients' perception of the world through the study of a few aspects of awareness. The aspects in focus of the study were disease awareness, metacognition, managing of everyday life, and as a complement, the agreement (calibration) between patients and their spouses on the studied aspects was considered. A mixed-method evaluation design was used involving 15 AD patients, their spouses, and 15 elderly healthy control subjects. The study comprised both a semistructured interview (AD patients and spouse) and a neuropsychological assessment (AD patients and control subjects). The patients were aware of their disease and able to report on their illness. Despite this awareness, they were unable to realize and manage the practical and cognitive implications of their impairment. The results also indicate that patients and spouses were not well calibrated regarding thoughts about the disease and problems in handling the cognitive deterioration. The findings of our study have relevance to patients' well being and how they manage everyday life. An open dialogue on these issues between spouses and in the care for AD patients would hopefully enhance quality of life for all parties involved.

PPN13: DELAYS IN NURSING HOME PLACEMENT FOR PATIENTS WITH ALZHEIMER'S DISEASE ASSOCIATED WITH TREATMENT WITH DONEPEZIL MAY HAVE HEALTH CARE COST-SAVING IMPLICATIONS

OBJECTIVES: Donepezil, an anti-dementia drug, has been associated with delays in nursing home placement (NHP) for patients with Alzheimer's disease (AD). This analysis explores the health care cost-saving implications of such treatment. METHODS: Information on the dates and reasons for NHP was obtained through follow-up interviews with caregivers and chart reviews of 763 AD patients who participated in three randomized, double-blind, placebo-controlled clinical trials and two subsequent open-label studies of donepezil. Patients were categorized according to their experiences in utilizing donepezil during the clinical trials and extension studies. Cox proportional hazards models (adjusted for age, gender, baseline Mini-Mental Status Examination scores, caregiver status and post clinical study use of cholinesterase inhibitors) were used to estimate adjusted survival functions from which median times to NHP were estimated for each donepezil use category. Analyses of the relationship between donepezil use and time to NHP were completed for both first dementia-related placement (data reported here) and for permanent placement (data similar). Standard nursing home cost data were applied to these results. RESULTS: For the least exposure group (dose <5 mg/day and/or used drug for less than 8 weeks total; n = 95), the median time to first dementia-related NHP was 43 months. Compared with this group, patients who received at least 5 mg/day of donepezil for 8 weeks or more had a significantly (p < 0.05) longer time to first dementia-related NHP. For patients who received donepezil for at least 36 weeks (12 weeks of double blind and 24 weeks of open-label treatment, for example), the median time was 73 months to first dementia-related NHP (RR = 0.458, p < 0.01). CONCLUSIONS: Because nursing home care has been reported as the principal cost driver in the care of AD patients, these delays to the time of entry into a nursing home associated with donepezil treatment may have important health care cost-saving implications.

Estimating the Costs of Caring for People with Alzheimer Disease in California: 2000-2040

The costs of caring for people with Alzheimer disease (AD) in California are estimated using data from a study of the costs of caring for community-resident and institutionalized people with AD, combined will prevalence and population projections. Costs for community-resident patients will increase 83 percent in the period 2000 ($23.4 billion) to 2020 ($42.8 billion), and will grow an additional 59 percent from 2020 to 2040 ($68.1 billion). Costs for AD patients in institutions will increase 84 percent from 2000 ($2.5 billion) to 2020 ($4.6 billion), and will grow an additional 61 percent from 2020 to 2040 ($7.4 billion), assuming the supply of nursing home beds meets projected demand. Total costs of caring for AD patients will nearly triple between 2000 and 2040. The rapid aging of the U.S. population makes more aggressive societal action necessary if the personal and societal burden of Alzheimer's disease is to be reduced in the future.

Evolving Standards in Patient and Caregiver Support

It has become increasingly clear that family members and others have enormous potential to contribute positively to the care of the patient suffering from Alzheimer disease (AD). Various methods such as respite services and day care as well as counseling and support groups have been shown to reduce caregiver stress and burnout. Moreover, there are many areas in which the informed, trained caregiver can contribute positively to, and even lead, the interdisciplinary ongoing care of AD patients. For example, the caregiver can help with memory aids, behavioral interventions, the maintenance of exercise and nutrition, healthcare proxies and housing arrangements, decisions about intensity of treatment, and the timely implementation of palliative care approaches. Caregivers skilled in such matters will increase the quality of life of the AD patient and reduce their dependency. Many support services and educational activities are known to help caregivers and their patients, yet their availability is variable, and it is unclear whose responsibility it is to organize and finance them.

Ensuring the adequacy of long term care of AD patients: Special challenges and advocacy mechanisms

The world is aging. The United Nations' has estimated an increase in those 65 years of age and older in the world from 6 percent of the total population in 1985 to 9.7 percent of the population by the year 2025. The growth in the elderly population is most significant among the oldest of the old. While the incidence of Alzheimer's disease (AD) is related to advanced age (as are other forms of dementia), it can be concluded that the aging of the world will result in an increase in the worldwide number of AD patients. For example, in the United States presently there are in excess of 2.5 million persons with AD and 100,000 AD patients are dying on a yearly basis-it is the fourth leading cause of death in the United States for the elderly, following heart disease, cancer, and stroke.2 Holmes et al project that the number of AD victims in the United States will increase to over 14 million persons by the year 2050.3 It has been estimated that one-third of all American families have at least one parent who has AD.4

Potential Prevention Strategies for Alzheimer Disease

Primary prevention trials for Alzheimer disease (AD) should be considered because of the substantial cost of caring for AD patients. Current clues to possible treatments include the potential use of antioxidants, estrogens, anti-inflammatory drugs, drugs designed to alter apolipoprotein E4 status, and compounds altering amyloid metabolism. Because of the expense of primary prevention trials, resources should be devoted to developing epidemiological clues for environmental loss in vivo and searching for additional epidemiological clues for environmental factors that may protect individuals from AD. A primary prevention trial would involve the recruitment of 4,000-5,000 subjects followed for 3-5 years at a cost of approximately $20 million. Alternatively, a primary prevention trial could be performed as an "add on" study to an existing clinical trial of a compound of interest currently being tested in an elderly population at substantially less cost.