Treatment Of Dementia Research Articles

Dietary Factors and Interventions for Cognitive Impairment and Dementia

Dietary Factors and Interventions for Cognitive Impairment and Dementia

Searching for new drugs to treat Alzheimer’s disease dementia through multiple pathways

Dementia is a group of diseases, including Alzheimer's disease (AD), vascular dementia, Lewy body dementia, frontotemporal dementia, Parkinson's disease dementia, metabolic dementia and toxic dementia. The treatment of dementia mainly includes symptomatic treatment by controlling the primary disease and accompanying symptoms, nutritional support therapy for repairing nerve cells, psychological auxiliary treatment, and treatment that improves cognitive function through drugs. Among them, drug therapy to improve cognitive function is important. This review focuses on introducing and commenting on some recent progress in exploring drugs to improve cognitive function, especially the new progress in drug treatment for AD. We mainly discuss the opportunities and challenges in finding and developing new therapeutic drugs from the aspects of acetylcholinesterase, N-methyl-D-aspartate glutamate receptor, amyloid protein, tau protein and chronic immune inflammation.

Virus-mediated delivery of single-chain antibody targeting TDP-43 protects against neuropathology, cognitive impairment and motor deficit caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion induced by permanent unilateral common carotid artery occlusion in mice was recently found to induce an age-dependent formation of insoluble cytoplasmic TDP-43 aggregates reminiscent of pathological changes found in human vascular dementia. In this model, the gradual deregulation of TDP-43 homeostasis in cortical neurons was associated with marked cognitive and motor deficits. To target the TDP-43-mediated toxicity in this model, we generated an adeno-associated virus vector encoding a single-chain antibody against TDP-43, called scFv-E6, designed for pan-neuronal transduction following intravenous administration. Injected prior to brain hypoperfusion, this tonic virus-mediated delivery of the scFv-E6 antibody reduced formation of cytoplasmic TDP-43 aggregates in cortical neurons, boosted levels of autophagy markers and attenuated microgliosis. Moreover, the novel object recognition and grip strength tests revealed that neuronal expression of scFv-E6 prevented the cognitive impairment and loss of motor performance caused by two-months of cerebral hypoperfusion. The robust protective effects of scFv-E6 antibody in this model suggest a key role of TDP-43 in neuronal damage and symptom phenotypes caused by chronic cerebral hypoperfusion. Accordingly, TDP-43 should be considered as a new therapeutic target in drug development, including antibody approaches, for treatment of vascular dementia.

DESIGNING A BIOEXPERIENTIAL PROGRAM FOR SAFETY, USABILITY, AND ACCEPTABILITY WITH DYADS WITH ADVANCED DEMENTIA

Abstract Dyadic psychosocial interventions that engage both persons living with dementia (PLWD) and care partners (CPs) are increasingly popular. Yet, designing dyadic interventions for advanced dementia is challenging due to mismatched abilities. Here, we describe the initial development and refinement of the Toolkit for Experiential well-beiNg in Dementia (TEND) intervention with a focus on design considerations for safety, usability, and acceptability. TEND is an online bioexperiential program (e.g., storytelling, digital art, and relaxing sounds and imagery) designed to engage PLWD and CPs together, to support positive affect, relationship satisfaction, and emotional well-being. Using a multi-phasic approach consistent with user-centered design, we conducted two focus groups with clinicians (N=10), two with PLWD-CP dyads (N=7), and one with CPs only (N=4) to inform an initial prototype. Then, we conducted eight rounds of workshops with 10 PLWD-CP dyads to inform intervention refinements. Rapid data analysis was used to analyze findings and quickly inform iterative design. Focus group participants highlighted design considerations to avoid inadvertently exacerbating behavioral and psychiatric symptoms; matching the context of use; and promoting individualization, familiar stimuli, immersion, and visual clarity of the online program. After development of an initial prototype, workshop participants informed refinements to include mixed methods of engagement (i.e., voice recognition, typing, and interactive movement); instructions, tutorials, and navigation guides; directive prompts; simplified language; and pleasant sounds. Overall, the program was perceived as safe and user feedback informed refinements to promote usability and acceptability. We highlight design elements of the TEND program that were responsive to iterative user feedback.

COMPARING HEALTH SYSTEM–BASED AND COMMUNITY-BASED DEMENTIA CARE: THE DEMENTIA CARE (D-CARE) STUDY

Abstract Despite the advent of new medications for treatment of dementia, the clinical care of those affected remains a challenge. Though several community-based and health system-based approaches have been developed to provide comprehensive care for patients living with dementia and their caregivers, the relative effectiveness of these approaches is unknown. The Dementia Care (D-CARE) Study is a pragmatic randomized trial comparing the effectiveness of three dementia care approaches at four clinical trial sites (CTS) over 18 months: 1) by nurse practitioners or physician assistants within a health care system, 2) by social workers or nurses at community-based organizations, or 3) usual care. D-CARE illustrates advantages (e.g., facilitation of recruitment with over 93% receiving active intervention) and disadvantages (e.g., CTS health systems needed to implement two interventions; because both active interventions have prior demonstrated effectiveness, the differences are likely to be smaller, requiring a larger sample size to have sufficient power) of comparative effectiveness research. The pragmatic design presented obstacles including funding for clinical positions, integrating interventions into workflows, and potential threats to fidelity; but the real-world settings will facilitate dissemination. COVID-19 introduced additional barriers to recruitment and retention. Strong commitment by study leaders, adaptability of research staff, and continuous engagement of patient and stakeholders at the CTS contributed to D-CARE’s success in enrolling 2,176 participants and high retention rates. D-CARE applied principles of community-based participatory research to continually refine materials to the study’s needs. D-CARE’s adaptations and successes demonstrate viable strategies for sustainability and scalability in real-world practices.

EXPLORING THE EFFECTIVENESS OF COGNITIVE STIMULATION THERAPY FOR DEMENTIA IN UNITED STATES, BRAZIL, AND HONG KONG

Abstract Cognitive Stimulation Therapy (CST) is a cost-effective non-pharmacological intervention for dementia developed in the United Kingdom. Though CST has been adopted and implemented all over the world, there has not been a study to evaluate its effectiveness across multiple counties. This study analyzes existing data from CST groups in USA, Hong Kong, and Brazil to evaluate the primary outcomes CST for persons with dementia. Paired sample t-tests were conducted to evaluate the effect of CST on cognition, quality of life, physical function, and depression across the countries. Among the USA CST groups (N=288), significant t-test were calculated for cognition, t(261) = -7.412, p< 0.01, quality of life, t(199) = -8.707, p< 0.01, and depression, t(254) = 6.347, p< 0.01. A non-significant t-test was calculated for physical function, t(103) = 1.262, p=0.21. Among the Hong Kong CST groups (N=408), significant t-tests were calculated for cognition, t(204) = 3.125, p< 0.01, depression, t(236) = 3.084, p< 0.01. However, non-significant t-tests were calculated for quality of life, t(376) = -0.614, p=0.539, physical function, t(84) = -0.888, p=0.377. On the other hand, among Brazil CST groups (N=47), significant t-test was calculated for cognition, t(46) = -2.961, p< 0.01. However, non-significant t-tests were calculated for quality of life, t(46) = -1.760, p=0.085, physical function, t(46) = -0.250, p=0.804, and depression, t(46) = 0.345, p=0.690. There are cultural and demographic factors that influence the effectiveness of interventions like CST. As CST is being implemented as a cost-effective non-pharmacological intervention for dementia and Alzheimer’s worldwide, its cultural applicability is worth exploring.

DEVELOPMENT AND OPTIMIZATION OF MECHANISTICALLY SOUND DEMENTIA CARE INTERVENTIONS

Abstract Optimizing care for persons living with dementia (PLWD) and their caregivers (CGs) is an urgent priority. A recent AHRQ report highlights the poor quality of existent dementia interventions emphasizing the need to develop methodologically sound interventions that test theory-based mechanisms hypothesized to underlie intervention effects. This symposium will describe methodology and applications of the NIH Stage Model and the Science Of Behavior Change (SOBC) experimental medicine approach and how they inform interventions for PLWD and their CGs. Dr. Cornelius will introduce SOBC and discuss complexities of specifying conceptual models, measuring mechanisms, and study methodology in a dyadic context. Dr. Vranceanu will introduce the NIH stage model and discuss the development and refinement of the Mindfulness and Self-Compassionate Care Program for stressed CGs of PLWD who endorse behavioral symptoms (NIH Stage 1A), showcasing mechanism and measure selection, feasibility testing, and first test of mechanistic target engagement. Dr. Mroz will describe a Stage 0 Appreciative Inquiry approach, in partnership with PLWD (mild-moderate), to define promising pathways for measuring and intervening to bolster purpose in the wake of a dementia diagnosis. Dr. Plys will present feasibility, mechanism engagement, and clinical outcome results of an NIH Stage 1B trial comparing a mindfulness mobile app to a podcast control for stressed CGs of PLWD. Dr. Berridge will describe an intervention’s non-linear pathway to Stage 1B mechanistic research to support empowered shared decision making about technology use for dementia care. The discussant, Dr. Rice will contextualize these findings within the larger literature and NIA funding opportunities.

Uncovering Hericenones from the Fruiting Bodies of Hericium erinaceus through Interdisciplinary Collaboration.

Hericium erinaceus is an edible and medicinal mushroom. Previously, we found hericenones C-H from the fruiting bodies and erinacines A-I from the mycelia of the fungus. These compounds stimulated nerve growth factor (NGF) synthesis both in vitro and in vivo; some have been suggested to be effective in the prevention and treatment of dementia. Recently, the total synthesis of hericenones C-H and their derivatives (1-4) was reported by one of the authors. We considered that the chemical synthetic route would also be reasonable as a biosynthetic pathway of the compounds. Based on the hypothesis, we investigated the endogenous existence of synthetic intermediates and products of the chemical synthesis in the fruiting bodies. The n-hexane-soluble part of the fruiting bodies of H. erinaceus was fractionated, and all the fractions were subjected to a product ion scan and multiple reaction monitoring (MRM) analysis by LC-MS/MS and compared to the authentic synthesized compounds. The analysis indicated the endogenous existence of 1-4 and the dehydrated form of 2 or 3. The dehydrated form was elucidated to be (Z)-5 by chemical synthesis, and a plausible biosynthetic pathway was proposed.

Targeting NLRP3 signaling with a novel sulfonylurea compound for the treatment of vascular cognitive impairment and dementia.

As a key inflammatory factor, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation and the progression of neurodegenerative diseases. Dysregulation of NLRP3 signaling can trigger various inflammatory responses in the brain, contributing to the development of neurodegenerative diseases such as ischemic stroke, vascular dementia (VaD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Therefore, the NLRP3 signaling pathway is a promising therapeutic target for the treatment of neurodegenerative diseases, including VaD. In this study, we investigated the therapeutic effects of a synthetic sulfonylurea NLRP3 inhibitor, AMS-17, in a VaD mouse model using bilateral common carotid artery stenosis (BCAS) and elucidated the underlying mechanisms. All mice were randomly divided into three groups: Sham, VaD + Vehicle, and VaD + AMS-17. Cognitive function was assessed using the Y-maze and Morris water maze (MWM) on the 50th day after BCAS. Brain sections and blood serum samples were collected for biomarker analysis and immunohistochemistry. Neurodegeneration, expressions of the molecules involved in the NLRP3 signaling pathways, tight junction proteins, and myelination were assessed using western blotting and immunofluorescence (IF). The levels of Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-4 (IL-4) in the blood were measured using ELISA. AMS-17 treatment improved cognitive function, enhanced blood-brain barrier (BBB) integrity, and promoted remyelination in VaD mice. Additionally, AMS-17 reduced neurodegeneration and decreased the expression of NLRP3 and its associated proteins, Apoptosis-associated speck-like protein (ASC), and cleaved caspase-1 in the brain. It also lowered pro-inflammatory TNF-α and IL-1β levels, while increasing the anti-inflammatory IL-4 level in the blood. The findings of this study provide the first promising evidence for the use of AMS-17 in VaD treatment in mice. This study introduces AMS-17 as a novel chemical scaffold with NLRP3 inhibitory activity, which can be further developed for the treatment of VaD in humans.

A Novel Neuroprotective Derived Peptide of Erythropoietin Improved Cognitive Function in Vascular Dementia Mice.

The effective therapeutics for vascular dementia are still lacking. Here, we designed a novel derived peptide of erythropoietin-DEPO and evaluated its safety, erythropoiesis effect, and neuroprotective effects in mice of vascular dementia. For evaluating the safety and erythropoiesis, DEPO was injected into naive C57BL6 mice (n = 5) for 4-8 weeks, and venous blood was collected at 1, 2, and 4 weeks after DEPO treatment. Neuroprotective effects of DEPO were studied in both cultured neurons and bilateral common carotid artery stenosis (BCAS) mice (n = 10/group). After 4-week DEPO administration, neurobehavioral tests and histology were applied to evaluate cognitive function and brain tissue damage of mice, respectively. Molecule docking, western blotting, pharmacological or genetic interference with EPOR, and JAK/STAT/AKT pathway were used to determine the mechanism of neuroprotective effects of DEPO. DEPO did not increase the hemoglobin concentration or red blood cell number in mice after 4-week treatment compared to the Vehicle group (p > 0.05). DEPO treatment alleviated spatial reference memory impairment and the anxiety level in mice (p < 0.05). Both gray and white matter injuries were significantly alleviated by DEPO treatment. DEPO activated JAK/STAT pathway in cultured neurons and protected neurons against chronic ischemia (p < 0.05). Pharmacological or genetic interference with JAK2 signaling or EPOR inhibited the pro-survival effect of DEPO on chronic ischemia neurons (p < 0.05). DEPO is a novel safe erythropoietin-derived peptide and exerted its neuroprotective effects in vascular dementia mice through activating EPOR and its downstream JAK/STAT signaling pathway. DEPO is a potential alternative agent for treatment of vascular dementia or chronic cerebral ischemia.

Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia.

Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer's disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive. In this review, we delve into the current evidence regarding the physiological properties of PV-INs and summarize the latest insights into how their loss contributes to cognitive decline in dementia, particularly focusing on AD and VD. Additionally, we discuss the influence of PV-INs on brain development, the variations in their characteristics across different types of dementia, and how their loss affects the etiology and progression of cognitive impairments. Ultimately, our goal is to provide a comprehensive overview of PV-INs and to consider their potential as novel therapeutic targets in dementia treatment.

Management of patients with cognitive impairment in old age

Cognitive impairment (CI) is one of the most common disorders in elderly. As the population ages, the prevalence of cognitive impairment CI is also increasing. The importance of early identification of individuals with mild CI (MCI) lies in the fact that timely diagnosis of these disorders increases the potential for secondary prevention and therapeutic intervention, which can delay or even prevent the onset of occupational and social maladaptation due to the development of dementia. The current principles of classification of the MCI and the criteria for its diagnosis are presented. Current approaches to the treatment of patients with CI are discussed. It is shown that treatment should start as early as possible and include both non-pharmacological and pharmacological approaches to improve cognitive abilities and prevent CI progression. The possibilities of modern neuroprotective and symptomatic therapy of MCI and the role of choline alfoscerate in the treatment of MCI and dementia are presented. The results of the multicenter placebo-controlled ASCOMALVA study are discussed, in which the addition of choline alfoscerate to donepezil therapy in patients with Alzheimer's disease and cerebrovascular disease helped to slow the progression of CI, reduce the severity of the disease, and had a positive effect on the behavioral functions and emotional status of both patients and their caregivers. In addition, a decrease in the progression of cerebral atrophy was observed. A new form of choline alfoscerate (Cerpechol) for oral administration is reported that may increase patients' compliance and can be used in patients with dysphagia.

The effectiveness of digital technology interventions for cognitive function in older adults: a systematic review and meta-analysis of randomized controlled trials.

Digital technology interventions (DTIs) are seen as promising interventions to prevent or delay cognitive decline in older adults, yet evidence from reviews is not conclusive. The aim of this study is to explore the effectiveness of DTIs in improving older adults' cognitive function while taking study design and intervention characteristics as moderators. We searched the PubMed, Embase, CINAHL, PsycINFO, and Scopus databases up to May 26, 2023. Only randomized controlled trials examined the effects of DTIs on cognitive function were included in our study. Standardized mean difference (SMD) and 95% confidence interval for outcomes were applied in meta-analyses and subgroup analyses. A risk of bias assessment was also conducted. Overall, 23 eligible studies with a total sample size of 1454 participants were included. We found that DTIs significantly improved global cognitive function (SMD = 0.479), attention and processing speed (SMD = 0.488), executive function (SMD = 0.287), immediate recall (SMD = 0.266), and working memory (SMD = 0.307). Our subgroup analyses revealed that DTIs were more effective for cognitively impaired subjects, and DTIs with specific intervention characteristics, such as the inclusion of cognitive standard tasks, virtual reality-based interventions, specialized settings, professional guidance, low/medium-density training, > 24 sessions, and sessions lasting > 30 min, were more effective for different cognitive domains. This study supported the effectiveness of DTIs in improving cognitive function in older adults aged 60 years old and over, which may be influenced by study design and intervention characteristics. These findings have important implications for clinical dementia prevention and treatment strategies targeted at specific cognitive domains.

Exploring the Combined Efficacy of Rivastigmine and Vitamin E in Dementia Care

With the increasing number of individuals affected by dementia, particularly Alzheimer's disease (AD), it is essential to discover new treatments. This review looks at the potential benefits of using rivastigmine and vitamin E together to manage dementia. Rivastigmine, a drug that boosts acetylcholine levels in the brain, helps improve memory and communication between nerve cells. Vitamin E, a powerful antioxidant, shields brain cells from damage induced by oxidative stress. Combined, these treatments may slow down the progression of dementia and enhance patient outcomes. The review details how rivastigmine and vitamin E work individually and presents clinical evidence supporting their combined use. It also highlights the potential benefits of this combination therapy in improving cognitive functions and reducing the decline in daily activities. Additionally, the paper outlines areas for future research, such as long-term effectiveness, optimal dosages, and real-world application, to fully understand and utilize this therapeutic combination. In conclusion, while current evidence is promising, Additional research is required to validate the effectiveness and enhance the application of rivastigmine and vitamin E in dementia treatment. This review emphasizes the need for ongoing studies to refine treatment approaches and elevate the quality of life for individuals with dementia.

Physicochemical Properties, Fatty Acid Profile and Estimation of Phospholipids by HPLC-ELSD Method in Seeds of &lt;i&gt;Abelmoschus esculentus&lt;/i&gt; and &lt;i&gt;Benincasa hispida&lt;/i&gt;

Background: Abelmoschus esculentus (Ae) and Benincasa hispida (Bh) are herbal plants has embarked its benefits in ayurveda medicine since history. Chemical compounds present in these two plant parts have numerous health benefits. Aim: In the present study seeds of the selected plants Ae and Bh are evaluated for its physicochemical, pharmacognostical, and analyzing fatty acid profile along with estimating important phospholipids such as Phosphatidyl Choline (PC) and Phosphatidyl Ethanolamine (PE) by HPLC-ELSD method. Methods: PC and PE are phospholipids which are the important components of cell membrane. PC and PE are involved in cell signaling, brain development, signal transduction, cell to cell communication and used for the synthesis of acetylcholine, which is a neurotransmitter. Hence, estimating PC and PE in the seeds of Ae and Bh will serve as an important data, and which will act as a source of memory enhancing components. Total lipids were extracted from the seeds using chloroform and methanol. The extracted lipids were subjected to column chromatography to estimate PC and PE. Using seed powder physicochemical and pharmacognostical values were evaluated. Results: Current study results show optimized physicochemical and pharmacognostical values. Fatty acids such as linoleic, palmitic and oleic acids make up the higher percentage. Importantly we could be able to estimate PC and PE by proposed HPLC-ELSD method, in Ae account for 24.6 % (PC) and 75.4% (PE), but unfortunately, we could not be able to estimate phospholipids in Bh by proposed method. Conclusion: The obtained results will serve as a parameter for the standardization of seeds and fixed oil obtained from seeds, with the estimation of phospholipids, which can be utilized as a potential source in the treatment of dementia, Alzheimer’s disease, Parkinson disease etc.

The pharmacoeconomic assessment of the rationality of the use of memantine and its combinations with acetylcholinesterase inhibitors in the treatment of dementia in Alzheimer’s disease in Ukraine

Aim. To conduct the pharmacoeconomic assessment of the rationality of using memantine and its combinations with acetylcholinesterase inhibitors in the treatment of dementia in Alzheimer’s disease in Ukraine. Materials and methods. Historical, analytical and comparative, systematic, graphic, logical, hypothetical-deductive, as well as marketing, pharmacoeconomic, and mathematical and statistical methods of analysis were used. The pharmacoeconomic studies were conducted using the cost-effectiveness method. CER and ICER indicators were calculated for dementia treatment regimens in Alzheimer’s disease containing memantine and its combinations with acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) in the period of 12 and 24 weeks of their use. The pharmacoeconomic analysis used data on the clinical effectiveness of dementia treatment regimens in Alzheimer’s disease presented in the Sochrane library (ID Number: CN-01071444; Accession Number: PUBMED 25932260e). Results. It was found that despite the clinical advantages of using the memantine+galantamine regimen proven by scientists according to the MMSE scale, the use of the memantine+rivastigmine regimen seemed to be rational (CER1 = 23.13 and CER2 = 34.57 USD/unit of increased efficiency). The clinical and economic benefits of using the memantine+galantamine regimen in the treatment of dementia patients with Alzheimer’s disease were proven in the 12- and 24-week regimen (MMSE scale). In the case of using the AADL scale, it was rational, from the point of view of economical use of resources, in the 12-week regimen of treating patients, the use of the memantine + rivastigmine regimen was less expensive (CER1 = 18.30 $/unit of AADL score reduction), while in the 24-week regime it was the memantine + placebo regimen (CER2 = $37.58 $/ unit of AADL score reduction). Conclusions. The research results presented can be used in forming drug purchases carried out by specialized healthcare institutions under the conditions of limited budget funding and growing needs of psychoneurological patients in effective medical and pharmaceutical care.

Stepwise identification of prodromal dementia: Testing a practical model for primary care.

Prodromal dementia is largely underdiagnosed in primary care. To develop a clinical model for detecting prodromal dementia within the operative boundaries of primary care practice. The study employed the Functional Activities Questionnaire (FAQ) and Montreal Cognitive Assessment (MoCA) to evaluate a "functional-cognitive" step-down screening model, in which the MoCA is administered subsequent to reported symptoms on the FAQ. It classified participants from the Alzheimer's Disease Imaging Initiative to three diagnostic categories: (1) healthy cognition (n = 396), (2) mild cognitive impairment without conversion (n = 430), and (3) prodromal dementia assessed 24 months before diagnosis (n = 164). Analyses indicated that the step-down model (Model 1) performed significantly better than an alternative model that applied the FAQ as a single measure (Model 2) and compared well with another model that administered both screening measures to all participants (Model 3). Gradient Boosting Trees classifications yielded the following estimations for Model 1/Model 2/ Model 3, respectively: Sensitivity = 0.87/0.77/0.89, Specificity = 0.68/0.47/0.70, PPV = 0.73/0.40/0.75, NVP = 0.84/0.81/0.87, F1 Score = 0.79/0.52/0.81, AUC = 0.78/0.67/0.79. These analyses support the proposed model. The study offers algorithms for validated measures, which were developed from a well characterized clinical sample. Their accuracy will likely improve further with new data from diverse clinical settings. These results can serve primary care in a timely manner in light of the recent advances in pharmacological treatment of dementia and the expected increase in demand for screening.

Antisense oligonucleotide‐based α‐synuclein targeting as a disease‐modifying treatment for Dementia with Lewy bodies (DLB) disease

Antisense oligonucleotide‐based α‐synuclein targeting as a disease‐modifying treatment for Dementia with Lewy bodies (DLB) disease

Utility of three cognitive screening tests to triage referrals to a dementia specialty clinic

AbstractBackgroundDue to the shortage of healthcare professionals with expertise in diagnosis and treatment of Alzheimer disease and related dementias, there are long wait times to be evaluated in dementia specialty clinics and no clear guidance about how to allocate limited resources. The purpose of this study was to examine utility of cognitive screening measures administered by clinic staff to determine level of cognitive impairment to aid in decisions about which patients may benefit from full diagnostic services.MethodsParticipants were 169 older adults who completed an intake interview, including a brief cognitive screening test, conducted by a neuropsychologist at a dementia specialty clinic. During the rooming process, clinic staff administered one of three cognitive screening measures, Quick Dementia Rating Scale (QDRS; n = 47), Quick Mild Cognitive Impairment (Qmci) screen (n = 70), and the BrainCheck Standard Battery (n = 52). After the intake interview, blinded to results of these cognitive screening measures, the neuropsychologist completed an initial impressions form indicating level of cognitive impairment (i.e., none, mild, possible dementia, definite dementia). A separate neuropsychologist, blinded to information from the intake interview, completed the same form based on results of each of the three cognitive screening measures and patient demographic information.ResultsBased on impressions from the intake interview, 27 patients were cognitively normal (CN), 67 had mild cognitive impairment (MCI), 32 had possible dementia, and 43 had definite dementia. Agreement on level of cognitive impairment between the intake interview and cognitive screening measures was 53% for QDRS (κ = .459, p &lt; .001), 41% for Qmci (κ = .423, p &lt; .001), and 48% for BrainCheck (κ = .539, p &lt; .001). Agreement improved notably for all three measures when level of cognitive impairment was limited to two groups (i.e., CN + MCI vs possible + definite dementia): 79% for QDRS (κ = .566), 77% for Qmci (κ = .537), and 83% for BrainCheck (κ = .655).ConclusionsCognitive screening measures administered by clinic staff and interpreted by dementia experts may have utility as time‐efficient, cost‐effective clinical decision support tools for the allocation of limited dementia diagnostic resources.

Fluid Biomarkers in Dementia Diagnosis.

This article familiarizes neurologists with the currently available CSF and plasma biomarkers for the diagnosis of dementia and diagnosis-dependent treatment decisions. For Alzheimer disease, the recent US Food and Drug Administration (FDA) approval of monoclonal antibody therapy has increased the urgency of confirming the pathologic diagnosis with biomarkers before initiating therapy. The new availability of disease-modifying therapies also highlights the need for biomarkers to monitor efficacy over time. Both of these needs have been partially addressed by the emergence of improved blood-based biomarkers for Alzheimer disease. Regarding other forms of dementia, the latest development is a CSF assay for aggregated α-synuclein, which permits the biomarker confirmation of synuclein pathology in Lewy body dementia. CSF biomarkers for the diagnosis of Alzheimer disease, Lewy body dementia, and Creutzfeldt-Jakob disease are well established. Blood-based biomarkers for dementia diagnosis are emerging and rapidly evolving. Sensitivity and specificity for diagnosis continue to improve, and they are being incorporated into diagnostic decisions. Fluid biomarkers for monitoring the efficacy of therapy are not yet established. Because serial CSF examinations are impractical, the validation of blood-based biomarkers of disease activity will be critical for addressing this unmet need.