Pharmacotherapy Of Dementia Research Articles

Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.

Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting the elderly. The most common forms are Alzheimer's disease, vascular dementia, and other (frontotemporal, Lewy body disease) dementias. The etiology of these multifactorial disorders involves complex interactions of various environmental and (epi)genetic factors and requires multiple forms of pharmacological intervention, including anti-dementia drugs for cognitive impairment, antidepressants, antipsychotics, anxiolytics and sedatives for behavioral and psychological symptoms of dementia, and other drugs for comorbid disorders. The pharmacotherapy of dementia patients has been characterized by a significant interindividual variability in drug response and the development of adverse drug effects. The therapeutic response to currently available drugs is partially effective in only some individuals, with side effects, drug interactions, intolerance, and non-compliance occurring in the majority of dementia patients. Therefore, understanding the genetic basis of a patient's response to pharmacotherapy might help clinicians select the most effective treatment for dementia while minimizing the likelihood of adverse reactions and drug interactions. Recent advances in pharmacogenomics may contribute to the individualization and optimization of dementia pharmacotherapy by increasing its efficacy and safety via a prediction of clinical outcomes. Thus, it can significantly improve the quality of life in dementia patients.

HTA52 Evaluation of Cost by TPS vs Pharmacotherapy of Dementia in Ukraine

HTA52 Evaluation of Cost by TPS vs Pharmacotherapy of Dementia in Ukraine

Replacement of leisure-time sedentary behavior with various physical activities and the risk of dementia incidence and mortality: A prospective cohort study

BackgroundWhether or not there is targeted pharmacotherapy for dementia, an active and healthy lifestyle that includes physical activity (PA) may be a better option than medication for preventing dementia. We examined the association between leisure-time sedentary behavior (SB) and the risk of dementia incidence and mortality. We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities. MethodsIn the UK Biobank, 484,169 participants (mean age = 56.5 years; 45.2% men) free of dementia were followed from baseline (2006–2010) through July 30, 2021. A standard questionnaire measured individual leisure-time SB (watching TV, computer use, and driving) and PA (walking for pleasure, light and heavy do-it-yourself activity, strenuous sports, and other exercise) frequency and duration in the 4 weeks prior to evaluation. Apolipoprotein E (APOE) genotype data were available for a subset of 397,519 (82.1%) individuals. A Cox proportional hazard model and an isotemporal substitution model were used in this study. ResultsDuring a median 12.4 years of follow-up, 6904 all-cause dementia cases and 2115 deaths from dementia were recorded. In comparison to participants with leisure-time SB <5 h/day, the hazard ratio ((HR), 95% confidence interval (95%CI)) of dementia incidence was 1.07 (1.02–1.13) for 5–8 h/day and 1.25 (1.13–1.38) for >8 h/day, and the HR of dementia mortality was 1.35 (1.12–1.61) for >8 h/day. A 1 standard deviation increment of sedentary time (2.33 h/day) was strongly associated with a higher incidence of dementia and mortality (HR = 1.06, 95%CI: 1.03–1.08 and HR = 1.07, 95%CI: 1.03–1.12, respectively). The association between sedentary time and the risk of developing dementia was more profound in subjects <60 years than in those ≥60 years (HR = 1.26, 95%CI: 1.00–1.58 vs. HR = 1.21, 95%CI: 1.08–1.35 in >8 h/day, p for interaction = 0.013). Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a 6% decreased risk and 9% decreased mortality from dementia, with exercise (e.g., swimming, cycling, aerobics, bowling) showing the strongest benefit (HR = 0.82, 95%CI: 0.78–0.86 and HR = 0.79, 95%CI: 0.72–0.86). Compared with APOE ε4 noncarriers, APOE ε4 carriers are more likely to see a decrease in Alzheimer's disease incidence and mortality when PA is substituted for SB. ConclusionLeisure-time SB was positively associated with the risk of dementia incidence and mortality. Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.

Феномен эксайтотоксичности как объект фармакологического воздействия при деменциях

Статья посвящена вопросам терапии деменции. Подробно рассматривается место в лечении данной патологии препарата группы адамантанов мемантина — неконкурентного низкоаффинного антагониста NMDA-рецепторов. Подчеркивается, что мемантин занимает совершенно особое место не только в фармакотерапии деменций, но и в нейрофармакологии в целом, представляя собой уникальный регулятор всей системы глутаматергической медиации, своего рода «адаптоген» в отношении глутаматзависимых процессов в центральной нервной системе и «корректор» реакций эксайтотоксичности. Результаты исследований применения мемантина показывают его эффективность при различных формах и при всех стадиях деменции, комплексность воздействия на все основные клинические синдромы (когнитивный, поведенческий, психоэмоциональный), долгосрочность клинических эффектов, сочетаемость с другими лекарственными средствами в рамках комбинированной терапии, хорошую переносимость и безопасность.

Препарати — інгібітори холінестерази в терапії деменцій: клініко-фармакологічні аспекти

У статті викладаються сучасні уявлення про фармакотерапію деменцій, зокрема про інгібітори ацетилхолінестерази (ІАХЕ), які сьогодні включені в усі світові рекомендації з лікування деменцій. Обґрунтуванню їх застосування на різних етапах когнітивних порушень присвячено значну кількість публікацій. На сьогоднішній день саме ІАХЕ виявилися єдиною групою лікарських засобів, що відповідають потребам клінічної практики, тобто здатні справляти клінічно значимий терапевтичний ефект при задовільному рівні побічної дії.

Resident-Level Predictors of Dementia Pharmacotherapy at Long-Term Care Admission: The Impact of Different Drug Reimbursement Policies in Ontario and Saskatchewan: Prédicteurs de la pharmacothérapie de la démence au niveau des résidents lors de l'hospitalisation dans des soins de longue durée : l'impact de différentes politiques de remboursement des médicaments en Ontario et en Saskatchewan.

Cholinesterase inhibitors (ChEIs) and memantine are approved for Alzheimer disease in Canada. Regional drug reimbursement policies are associated with cross-provincial variation in ChEI use, but it is unclear how these policies influence predictors of use. Using standardized data from two provinces with differing policies, we compared resident-level characteristics associated with dementia pharmacotherapy at long-term care (LTC) admission. Using linked clinical and administrative databases, we examined characteristics associated with dementia pharmacotherapy use among residents with dementia and/or significant cognitive impairment admitted to LTC facilities in Saskatchewan (more restrictive reimbursement policies; n = 10,599) and Ontario (less restrictive; n = 93,331) between April 1, 2009, and March 31, 2015. Multivariable logistic regression models were utilized to assess resident demographic, functional, and clinical characteristics associated with dementia pharmacotherapy. On admission, 8.1% of Saskatchewan residents were receiving dementia pharmacotherapy compared to 33.2% in Ontario. In both provinces, residents with severe cognitive impairment, aggressive behaviors, and recent antipsychotic use were more likely to receive dementia pharmacotherapy; while those who were unmarried, admitted in later years, had a greater degree of frailty, and recent hospitalizations were less likely. The direction of the association for older age, rural residency, medication number, and anticholinergic therapy differed between provinces. While more restrictive criteria for dementia pharmacotherapy coverage in Saskatchewan resulted in fewer residents entering LTC on dementia pharmacotherapy, there were relatively few differences in the factors associated with use across provinces. Longitudinal studies are needed to assess how differences in prevalence and characteristics associated with use impact patient outcomes.

Problems Associated with the Measurement of Neuropsychiatric Symptoms of Dementia

Neuropsychiatric symptoms (NPS) affect nearly all persons living with dementia (PLWD) at some point during the course of the disease. Given the absence of a cure or effective pharmacotherapy for dementia, it is particularly important to prevent, measure, track, and manage NPS in dementia care. Unfortunately, these efforts are hindered by inconsistent operational definitions and measurement tools for numerous neuropsychiatric symptoms. This review examines agitation, aggression, restlessness, and rejection of care as examples of NPS that are not consistently measured across research studies and scales. The results of a computerized search of peer-reviewed published studies of assessment tools measuring these NPS are reported. The differences in operational definitions and conceptual underpinnings of the four NPS are highlighted through comparisons of seven agitation measurements and four aggression measurements, and through a discussion of the inappropriate nesting of restlessness and rejection of care within co-occurring – but distinct – NPS. Universally-accepted consensus definitions of NPS are needed in order to develop accurate measurements around these definitions. Until that time, inconsistent nosology, conceptualization, and measurement will continue to confound our understanding of the prevalence and disease burden of these behaviors and hinder the development of effective interventions.

Strategy for Peptide Drug Delivery via Nose-to-Brain Transport Pathways: Challenges to Pharmacotherapy for Dementia

Strategy for Peptide Drug Delivery via Nose-to-Brain Transport Pathways: Challenges to Pharmacotherapy for Dementia

Important regulatory function of transient receptor potential ankyrin 1 receptors in age-related learning and memory alterations of mice

Expression of the transient receptor potential ankyrin 1 (TRPA1) receptor has been demonstrated not only in the dorsal root and trigeminal ganglia but also in different brain regions (e.g., hippocampus, hypothalamus, and cortex). However, data concerning their role in neurodegenerative and age-related diseases of the CNS is still indistinct. The aim of our study was to investigate the potential role of TRPA1 in a mouse model of senile dementia. For the investigation of changes during aging, we used male young (3–4-month-old) and old (18-month-old) wild-type (TRPA1+/+;WT) and TRPA1 receptor gene-deleted (TRPA1−/−) mice. Novel object recognition (NOR) test as well as Y maze (YM), radial arm maze (RAM), and Morris water maze (MWM) tests were used to assess the decline of memory and learning skills. In the behavioral studies, significant memory loss was detected in aged TRPA1+/+ mice with the NOR and RAM, but there was no difference measured by YM and MWM tests regarding the age and gene. TRPA1−/− showed significantly reduced memory loss, which could be seen as higher discrimination index in the NOR and less exploration time in the RAM. Furthermore, young TRPA1−/− animals showed significantly less reference memory error in the RAM and notably higher mobility in NOR, RAM, and YM compared with the age-matched WTs. Our present work has provided the first evidence that TRPA1 receptors mediate deteriorating effects in the old age memory decline. Understanding the underlying mechanisms could open new perspectives in the pharmacotherapy of dementia.

Caregivers\u2019 perspectives and experiences of withdrawing acetylcholinesterase inhibitors and memantine in advanced dementia: a qualitative analysis of an online discussion forum

BackgroundThere is considerable uncertainty surrounding the medications used to delay the progression of dementia, especially their long-term efficacy and when to withdraw treatment with these agents. Current research regarding the optimal use of antidementia medication is limited, contributing to variability in practice guidelines and in clinicians’ prescribing practices. Little is currently known about the experiences encountered by caregivers of people with dementia after antidementia medication is withdrawn.AimTo investigate the experiences and perspectives of carers and family members when antidementia medications (cholinesterase inhibitors and/or memantine) are stopped, by analysing archived threads and posts of an online discussion forum for people affected by dementia.MethodsArchived discussions from Talking Point, an online discussion forum hosted by the Alzheimer’s Society UK, were searched for threads discussing antidementia medication withdrawal and relevant threads were analysed thematically using the Framework method. Participant demographics were not established due to usernames which ensured anonymity.ResultsFour key themes emerged: (1) expectations about withdrawal, (2) method of withdrawal, (3) clinical condition on withdrawal, and (4) the effect of withdrawal on caregivers.ConclusionsOnline discussion forums such as Talking Point provide dementia carers with an outlet to seek help, offer advice and share experiences with other members. The study findings highlight the complexity surrounding optimising dementia pharmacotherapy and antidementia medication withdrawal, highlighting the need for treatment to be person-centred and highly individualised.

Current management tactics for patients with dementia

Dementia develops as a result of continuous long-term progression of less severe cognitive impairment (CI). Social and psychological methods (neurocognitive stimulation and neurocognitive training) are the mainstay of treatment for dementia. At the moment, there are no drugs both to cure dementia and to stop the degeneration of nerve tissue. Modern pharmacotherapy for dementia aims to maintain cognitive functions in the patient for as long as possible and to slow down disability, thus ensuring higher living standards. CI therapy most often consists of compensation for cognitive defect. Among the whole variety of pharmacological agents, the effective drugs to treat dementia are only two groups, such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. Atypical neuroleptics are employed for the treatment of psychotic disorders; antidepressants from a group of selective serotonin reuptake inhibitors are for depression. Cognitive behavioral therapy and cognitive stimulation deserve special attention. A high educational level and physical, social, and intellectual and activities can prevent dementia.

Nose-to-Brain Delivery of Peptide Drugs Enhanced by Coadministration of Cell-penetrating Peptides: Therapeutic Potential for Dementia.

Recent reports suggest that peptide drugs such as insulin have the potential to serve as therapeutics in neurodegenerative diseases such as Alzheimer's disease. However, the transport of these drugs to the therapeutic target, the brain, is significantly hindered by the blood-brain barrier (BBB). Intranasal administration appears to be an ideal solution for drug delivery to the brain, bypassing the BBB, however the entry of peptide drugs into neuronal and epithelial cells in the olfactory mucosa remains low. In this study, we therefore examined whether intranasal coadministration of cell-penetrating peptides (CPPs) could improve nose-to-brain drug transport. In both mice and rats, we found that direct transport of insulin into the brain was significantly facilitated when coadministered with amphipathic CPP penetratin, and eventually insulin reached the deeper regions of the brain such as the hippocampus. In the mouse line senescence-accelerated mouse prone-8 (SAMP8), spatial learning tests demonstrated that long-term intranasal coadministration of insulin with penetratin improved mild memory loss in the early stages of dementia. In contrast, the severe cognitive dysfunction in the aged SAMP8 mice was preserved despite intranasal coadministration of insulin with penetratin. The immunohistological examination of the hippocampus suggested that enhanced nose-to-brain delivery of insulin had a partial neuroprotective effect but unexpectedly increased amyloid β plaque deposition. In conclusion, intranasal coadministration of insulin with CPPs has the potential to serve as a therapeutic for mild cognitive dysfunction. To identify suitable pharmacotherapy for dementia with severe pathology, further studies of nose-to-brain delivery of molecularly appropriate biopharmaceuticals are necessary.

PMH46 - Mental Health - Costs and Treatment Penetration Across Europe

Mental health disorders are becoming important drivers in costs and resource use among non-communicable diseases. This trend will continue due to aging population. The authors evaluated pharmacotherapy costs, accessibility and treatment penetration for specific mental health disorders (schizophrenia, depression and dementia) across Europe. Based on published statistics and IMS data we calculated No. of mental health specialists, resource use and medication penetration in 29 European countries. Penetration was calculated in standard units per capita. There is a wide range of psychiatrists per 100 000 inhabitants (from 1 in Turkey to 30 in Switzerland), costs spent for mental health (% from healthcare) also differ significantly from 2 % (Bulgaria) to almost 14 % (UK). Average European costs for pharmacotherapy (ATC groups N3-N7) is 25 Euro/capita (2013 data); from 6 € in Russia to 57 € in Switzerland. Since 2009 the penetration of atypical antipsychotics steadily increases across Europe from 48 % among all antipsychotics (2009) to 56 % (2013). We however found differences in individual countries (46 % penetration in Slovenia; 69 % penetration in Hungary). The average annual European consumption of antidepressants is 18 units per capita (2 units in Russia; 42 units in the UK). SSRIs represent approximately 50 % of all antidepressants in the majority of countries. Penetration of pharmacotherapy for dementia (ATC group N7D1) is poor across Europe except Finland and Greece. In almost all countries it is below 50 % if a hypothetical common prevalence of 1.17 % is assumed. Our findings indicate unequal access, treatment penetration and allocation of financial resources across 29 evaluated European countries.

Pharmacotherapy for Dementia: A Practical Approach to the Use of Cholinesterase Inhibitors and Memantine.

Cholinesterase inhibitors and memantine are the only classes of drugs approved for the treatment of dementia due to Alzheimer's disease. This article provides evidence-based recommendations to address the issues regarding the use of cholinesterase inhibitors and memantine in clinical practice. It includes their efficacy, timing, assessment, use in institutionalized patients, combined use, and use in other dementia types. However, most of the studies are of short duration (<1year) and are mainly focused on cognitive and global improvement, whereas the practical issue of their use in daily practice such as optimal duration of treatment, long-term efficacy and delaying institutionalization are limited.

Pharmacotherapy of dementia in Germany: Results from a nationwide claims database

In 2011, about 1.1–1.4 million patients with dementia were living in Germany, a number expected to rise to three million by 2050. Dementia poses a major challenge to the healthcare system and neuropharmacological service provision. The aim of this study was to determine prescription rates for anti-dementia drugs as well as for neuroleptics, sedative-hypnotics and antidepressants in dementia using the complete nationwide outpatient claims data pertaining to the services of statutory health insurance. We controlled for gender, age, dementia diagnosis, physician specialty (general practitioner GP versus neuropsychiatry specialist physician NPSP), and rural and urban living area. In about one million prevalent dementia patients (N=1,014,710) in 2011, the prescription prevalence rate of anti-dementia drugs was 24.6%; it varied with gender, age, and diagnosis (highest in Alzheimer’s disease; 42%), and was higher in patients treated by NPSPs (48% vs. 25% in GPs). At the same time, we found an alarmingly high rate of treatment with neuroleptics in dementia patients (35%), with an only slightly decreased risk in patients treated exclusively by NPSPs (OR=0.86). We found marginal differences between rural and urban areas. Our results show that the majority of anti-dementia drug prescriptions appear guideline-oriented, yet prescription rates are overall comparatively low. On the other hand, neuroleptic drugs, which are associated with excess morbidity and mortality in dementia, were prescribed very frequently, suggesting excess use given current guidelines. We therefore suggest that guideline implementation measures and increasing quality control procedures are needed with respect to the pharmacotherapy of this vulnerable population.

Persistence and adherence with dementia pharmacotherapy: relevance of patient, provider, and system factors.

This paper provides a comprehensive review of studies examining adherence and (or) persistence with dementia pharmacotherapy during the past decade, including a summary of the key patient-, drug-, system-, and provider-level factors associated with these measures. Estimates of adherence and 1-year persistence to these drugs have ranged from 34% to 94% and 35% to 60%, respectively. Though many studies reported nonsignificant associations, there are data suggesting that patient age, sex, ethnoracial background, socioeconomic status, and region-specific reimbursement criteria, as well as the extent and quality of interactions among patients, caregivers, and providers, may influence persistence with pharmacotherapy. As many studies relied on administrative data, limited information was available regarding the relevance of patient's cognitive and functional status or the importance of caregiver involvement or assistive devices to adherence or persistence.

Geriatric Psychiatry: What's in a Name, and Five Concerns about DSM-5.

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Patterns and Determinants of Dementia Pharmacotherapy in a Population-Based Cohort of Home Care Clients

Little is known about the needs of older home care clients with dementia or their key quality of care issues, including their use of pharmacotherapy for Alzheimer's disease. The objectives of this study were to (1) describe the sociodemographic, psychosocial, and health characteristics of clients with dementia (relative to two control subgroups) from a population-based home care cohort; and, (2) determine the distribution and associated characteristics of cholinesterase inhibitor (ChEI) and/or memantine use among dementia clients overall and according to medication class, comorbid illness, and year of assessment. This cross-sectional study included all home care clients aged 50 years or older assessed with the Resident Assessment Instrument-Home Care (RAI-HC) in Ontario, Canada from January 2003 to December 2010. Multivariable logistic regression models were used to identify factors associated with receiving a dementia medication (a ChEI and/or memantine). There were 104,802 (21.5 %) clients with a diagnosis of dementia, 92,529 (18.9 %) cognitively impaired clients without a dementia diagnosis, and 290,929 (59.6 %) cognitively intact clients. Relative to the comparison groups, dementia clients were more likely to have reported conflicts with others, a distressed caregiver, greater levels of cognitive and functional impairment, and to exhibit wandering, aggressive behaviors, anxiety, hallucinations or delusions, and swallowing problems. Approximately half of dementia clients were taking a dementia medication, most commonly donepezil. Characteristics most strongly associated with use of ChEI monotherapy included age greater than 64 (especially 75-84), absence of economic barriers, availability of a primary caregiver, year of assessment, moderate to severe cognitive impairment, relative independence in function, health stability, no depressive symptoms or hallucinations/delusions, no recent hospitalization, use of at least 9 medications, the absence of chronic health and neurological conditions, and the use of an antipsychotic or antidepressant. For combination therapy, strong positive associations were observed for younger age, year of assessment, increasing cognitive impairment, presence of a primary caregiver, male sex, absence of economic barriers, use of at least 9 medications, and various indicators of positive health status (e.g., stability in health, absence of chronic health and neurological conditions, and no recent hospitalization). The percentage of clients receiving ChEIs increased with cognitive impairment scores but declined slightly at the highest level of impairment, whereas the percentage receiving memantine increased with cognitive impairment level. The number and percentage of dementia clients receiving any pharmacotherapy increased during the study interval. We observed a relatively high prevalence of dementia-specific pharmacotherapy among Ontario long-stay home care clients as well as significant variation in utilization patterns by select sociodemographic, functional, and clinical characteristics, and over time. While physicians generally followed recommended guidelines regarding appropriate dementia pharmacotherapy, continued efforts to monitor practice patterns are required among vulnerable older adults across care settings.

Interação medicamentosa e a farmacoterapia de pacientes geriátricos com síndromes demenciais

OBJETIVO: Investigar as possíveis interações medicamentosas, a fim de identificar os prováveis eventos adversos relacionados à farmacoterapia das síndromes demenciais. METODOLOGIA: A amostra foi constituída por 48 idosos com idade igual ou superior a 60 anos, portadores de síndromes demenciais atendidos no grupo terapêutico da equipe multiprofissional do Instituto Paulista de Geriatria e Gerontologia (IPGG). A primeira etapa foi a descrição da farmacoterapia geriátrica dos pacientes com síndromes demenciais. A segunda foi a análise estatística dos dados coletados com base no pacote Stata® 9.0, adotando-se p&lt;0,001, e a análise das interações medicamentosas foi baseada na utilização do programa Lexi-Interact™. RESULTADOS: Dos pacientes avaliados, verificou-se predomínio de pacientes do gênero feminino (66,7%). Em ambos os gêneros, a demência de Alzheimer foi o diagnóstico de maior prevalência, sendo 60% nas mulheres e 80% nos homens. Também se verificou maior adesão nos pacientes com diagnóstico de Alzheimer (81,8%). No que diz respeito aos medicamentos utilizados, verificaram-se 41 diferentes fármacos prescritos. Entre eles, os mais usados foram os do sistema cardiovascular (30,8%), seguidos dos medicamentos que atuam no nível central (29,8%). A polifarmácia foi verificada em 73,3% dos pacientes, mais predominante em pacientes do sexo feminino (54,5%), portadoras da demência de Alzheimer (72,7%), com grau moderado (50%). Entre as interações medicamentosas, destacaram-se as decorrentes do uso concomitante de medicamentos anti-hipertensivos (30,5%), dentre os quais os inibidores da enzima conversora de angiotensina (IECA) e os diuréticos (2,2%). CONCLUSÃO: A interação medicamentosa, como evento precursor do uso de medicamentos, pode resultar em efeitos potencialmente perigosos, como visto nas interações medicamentosas mediadas no uso de medicamentos hipotensores, cujo evento tem relação indireta com o grau de demência, e consequentemente comprometendo a evolução clínica dos pacientes diagnosticados como portadores de síndromes demenciais.

Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies

Cognitive impairment, including dementia, is a common but poorly recognized problem among patients with end-stage renal disease (ESRD), affecting 16-38% of patients. Dementia is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD; thus, recognizing and effectively managing cognitive impairment may improve clinical care. Dementia screening strategies should take into account patient factors, the time available, the timing of assessments relative to dialysis treatments, and the implications of a positive screen for subsequent management (for example, transplantation). Additional diagnostic testing in patients with cognitive impairment, including neuroimaging, is largely based on the clinical evaluation. There is limited data on the efficacy and safety of pharmacotherapy for dementia in the setting of ESRD; therefore, decisions about the use of these medications should be individualized. Management of behavioral symptoms, evaluation of patient safety, and advance care planning are important components of dementia management. Prevention strategies targeting vascular risk factor modification, and physical and cognitive activity have shown promise in the general population and may be reasonably extrapolated to the ESRD population. Modification of ESRD-associated factors such as anemia and dialysis dose or frequency require further study before they can be recommended for treatment or prevention of cognitive impairment.