The Influence of Multimorbidity on Clinical Progression of Dementia in a Population-Based Cohort

Introduction

Co-occurrence with other chronic diseases may influence the progression of dementia, especially in case of multiple chronic diseases. We aimed to verify whether multimorbidity influenced cognitive and daily functioning during nine years after dementia diagnosis compared with the influence in persons without dementia.

Methods

In the Kungsholmen Project, a population-based cohort study, we followed 310 persons with incident dementia longitudinally. We compared their trajectories with those of 679 persons without dementia. Progression was studied for cognition and activities of daily life (ADLs), measured by MMSE and Katz Index respectively. The effect of multimorbidity and its interaction with dementia status was studied using individual growth models.

Results

The mean (SD) follow-up time was 4.7 (2.3) years. As expected, dementia related to both the decline in cognitive and daily functioning. Irrespective of dementia status, persons with more diseases had significantly worse baseline daily functioning. In dementia patients having more diseases also related to a significantly faster decline in daily functioning. Due to the combination of lower functioning in ADLs at baseline and faster decline, dementia patients with multimorbidity were about one to two years ahead of the decline of dementia patients without any co-morbidity. In persons without dementia, no significant decline in ADLs over time was present, nor was multimorbidity related to the decline rate. Cognitive decline measured with MMSE remained unrelated to the number of diseases present at baseline.

Conclusion

Multimorbidity was related to baseline daily function in both persons with and without dementia, and with accelerated decline in people with dementia but not in non-demented individuals. No relationship of multimorbidity with cognitive functioning was established. These findings imply a strong interconnection between physical and mental health, where the greatest disablement occurs when both somatic and mental disorders are present.     

Genetic background modifies CNS‐mediated sensorimotor decline in the AD‐BXD mouse model of genetic diversity in Alzheimer's disease

Many patients with Alzheimer's dementia (AD) also exhibit noncognitive symptoms such as sensorimotor deficits, which can precede the hallmark cognitive deficits and significantly impact daily activities and an individual's ability to live independently. However, the mechanisms underlying sensorimotor dysfunction in AD and their relationship with cognitive decline remains poorly understood, due in part to a lack of translationally relevant animal models. To address this, we recently developed a novel model of genetic diversity in Alzheimer's disease, the AD‐BXD genetic reference panel. In this study, we investigated sensorimotor deficits in the AD‐BXDs and the relationship to cognitive decline in these mice. We found that age‐ and AD‐related declines in coordination, balance and vestibular function vary significantly across the panel, indicating genetic background strongly influences the expressivity of the familial AD mutations used in the AD‐BXD panel and their impact on motor function. Although young males and females perform comparably regardless of genotype on narrow beam and inclined screen tasks, there were significant sex differences in aging‐ and AD‐related decline, with females exhibiting worse decline than males of the same age and transgene status. Finally, we found that AD motor decline is not correlated with cognitive decline, suggesting that sensorimotor deficits in AD may occur through distinct mechanisms. Overall, our results suggest that AD‐related sensorimotor decline is strongly dependent on background genetics and is independent of dementia and cognitive deficits, suggesting that effective therapeutics for the entire spectrum of AD symptoms will likely require interventions targeting each distinct domain involved in the disease.     

Poor Decision Making Is a Consequence of Cognitive Decline among Older Persons without Alzheimer's Disease or Mild Cognitive Impairment

Objective

Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment.

Methods

Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams.

Results

Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment).

Conclusions

Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment.     

Virtual navigation in humans: the impact of age, sex, and hormones on place learning

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.     

Feelings of Hopelessness in Midlife and Cognitive Health in Later Life: A Prospective Population-Based Cohort Study

BackgroundSeveral studies have found depression and depressive feelings to be associated with subsequent dementia. As dementias typically have a long preclinical development phase, it has been difficult to determine whether depression and depressive feelings reflect a concurrent underlying dementia disease, rather than playing a causative role. Our aim was to investigate hopelessness, one dimension of depressive feelings, and evaluate the likelihood of a prodromal versus a causative role of hopelessness feelings in dementia development.MethodsWe invited a random sample of 2000 survivors from a representative population in Eastern Finland, originally investigated in midlife between 1972 and 1987, for re-examination an average of 21 years later. The age of the 1449 persons who accepted the invitation was between 39 and 64 years (mean 50.4 years) in midlife and between 65 and 80 (mean 71.3) at follow-up. To measure feelings of hopelessness in midlife and at follow-up, the participants indicated their level of agreement to two statements about their own possible future. We used logistic regression to investigate the association between the combined scores from these two items and cognitive health at follow-up, while adjusting for several health and life-style variables from midlife and for apolipoprotein E4 (ApoE4) status, depression and hopelessness feelings at follow-up. We compared the associations with late-life cognitive health when feelings of hopelessness were either measured in midlife or at the follow-up. In addition we analyzed the changes in hopelessness scores from midlife to follow-up in participants who were either cognitively healthy or impaired at follow-up.ResultsWe found higher levels of hopelessness in midlife, but not at follow-up, to be associated with cognitive impairment at follow-up; the adjusted odds ratio for each step of the five-level hopelessness scale was 1.30 (95% confidence interval 1.11–1.51) for any cognitive impairment and 1.37 (1.05–1.78) for Alzheimer’s disease. These associations remained significant also after the final adjustments for depressive feelings and for hopelessness at follow-up. The individual changes in hopelessness scores between midlife and follow-up were not systematically related to cognitive health at the follow-up.ConclusionOur results suggest that feelings of hopelessness already in midlife may have long-term implications for cognitive health and increase the risk of Alzheimer’s disease in later life.     

Increased Plasma Levels of Heat Shock Protein 70 Associated with Subsequent Clinical Conversion to Mild Cognitive Impairment in Cognitively Healthy Elderly

Background and Aims

Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline.

Methods

Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed.

Results

After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001).

Conclusions

These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly.     

Random change point model for joint modeling of cognitive decline and dementia

We propose a joint model for cognitive decline and risk of dementia to describe the pre-diagnosis phase of dementia. We aim to estimate the time when the cognitive evolution of subjects in the pre-dementia phase becomes distinguishable from normal evolution and to study whether the shape of cognitive decline depends on educational level. The model combines a piecewise polynomial mixed model with a random change point for the evolution of the cognitive test and a log-normal model depending on the random change point for the time to dementia. Parameters are estimated by maximum likelihood using a Newton-Raphson-like algorithm. The expected cognitive evolution given age to dementia is then derived and the marginal distribution of dementia is estimated to check the log-normal assumption.     

Are optimal levels of testosterone associated with better cognitive function in healthy older women and men?

Background

Sex steroids can positively affect the brain and from this it would follow that high levels of sex steroids could be associated with better cognitive function in older men and women.

Methods

This Healthy Ageing Study sample comprised of 521 older participants (51% women) without dementia at baseline, with an age range from 64 to 94 years. Testosterone and sex hormone binding globulin were measured using the automated Immulite 2000 and analyzed in association with baseline memory, global cognitive function and decline (assessed using the Mini-Mental Status Examination or MMSE) and controlling for potential confounds such as age, education, vascular disease, smoking, diabetes, thyroid function, and body mass index.

Results

In healthy older men and women, optimal levels of testosterone were associated with better MMSE scores at baseline. Follow-up analyses indicated that in men, low testosterone levels (OR = .94, 95% CI = .88 to 1.00) were a risk factor for a sharp cognitive decline after 2 years, perhaps indicative of dementia. Associations were independent of covariates and baseline MMSE. Conversely, women at risk for a sharp drop in cognitive function showed some evidence for higher calculated free testosterone levels at baseline.

Conclusions

Results replicate earlier cross-sectional findings that high levels of sex steroids are not associated with better cognitive function in older people. In men, age accelerated endocrinological change could be associated with dementia pathology.

General significance

These data do not support increasing testosterone levels to prevent cognitive decline in men and women over 65 years of age.     

Barriers encountered during enrollment in an internet-mediated randomized controlled trial

Background

Research evidence from observational studies suggests that cognitive activity reduces the risk of cognitive impairment in later life as well as the rate of cognitive decline of people with dementia. The Promoting Healthy Ageing with Cognitive Exercise (PACE) study has been designed to determine whether a cognitive activity intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment (MCI).

Methods/Design

The study will recruit 160 community-dwelling men and women aged 65 years of age or over with mild cognitive impairment (MCI). Participants will be randomly allocated to two treatment groups: non-specific education and cognitive activity. The intervention will consist of ten 90-minute sessions delivered twice per week over a period of five weeks. The primary outcome measure of the study is the change from baseline in the total score on the Cambridge Cognitive Score (CAMCOG). Secondary outcomes of interest include changes in memory, attention, executive functions, mood and quality of life. Primary endpoints will be collected 12, 52 and 104 weeks after the baseline assessment.

Discussion

The proposed project will produce the best available evidence on the merits of increased cognitive activity as a strategy to prevent cognitive decline among older adults with MCI. We anticipate that the results of this study will have implications for the development of evidence-based preventive strategies to reduce the rate of cognitive decline amongst older people at risk of dementia.

Trial registration

ACTRN12608000556347     

Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

Introduction

An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline.

Methods

Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined.

Results

All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine.

Discussion

Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.     

Peripheral inflammatory biomarkers are associated with cognitive function and dementia: Framingham Heart Study Offspring cohort

Inflammatory protein biomarkers induced by immune responses have been associated with cognitive decline and the pathogenesis of Alzheimer's disease (AD). Here, we investigate associations between a panel of inflammatory biomarkers and cognitive function and incident dementia outcomes in the well-characterized Framingham Heart Study Offspring cohort. Participants aged ≥40 years and dementia-free at Exam 7 who had a stored plasma sample were selected for profiling using the OLINK proteomics inflammation panel. Cross-sectional associations of the biomarkers with cognitive domain scores (N = 708, 53% female, 22% apolipoprotein E (APOE) ε4 carriers, 15% APOE ε2 carriers, mean age 61) and incident all-cause and AD dementia during up to 20 years of follow-up were tested. APOE genotype-stratified analyses were performed to explore effect modification. Higher levels of 12 and 3 proteins were associated with worse executive function and language domain factor scores, respectively. Several proteins were associated with more than one cognitive domain, including IL10, LIF-R, TWEAK, CCL19, IL-17C, MCP-4, and TGF-alpha. Stratified analyses suggested differential effects between APOE ε2 and ε4 carriers: most ε4 carrier associations were with executive function and memory domains, whereas most ε2 associations were with the visuospatial domain. Higher levels of TNFB and CDCP1 were associated with higher risks of incident all-cause and AD dementia. Our study found that TWEAK concentration was associated both with cognitive function and risks for AD dementia. The association of these inflammatory biomarkers with cognitive function and incident dementia may contribute to the discovery of therapeutic interventions for the prevention and treatment of cognitive decline.     

Longitudinal Associations between Physical and Cognitive Performance among Community-Dwelling Older Adults

To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.     

Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency

Background

Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer''s disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands.

Methods

Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated.

Results

Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics.

Conclusion

Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.     

A prospective study of cognitive health in the elderly (Oregon Brain Aging Study): effects of family history and apolipoprotein E genotype.

The oldest old are the fastest-growing segment of our population and have the highest prevalence of dementia. Little is known about the genetics of cognitive health in the very old. The aim of this study was to determine whether the genetic risk factors for Alzheimer disease (AD)--namely, apolipoprotein E (APOE) epsilon4 allele and a family history of dementia-continue to be important factors in the cognitive health of the very old. Case-control studies suggest that the effect of genetic factors diminishes at age >75 years. The present prospective study provided evidence to the contrary. We studied 114 Caucasian subjects who were physically healthy and cognitively intact at age 75 years and who were followed, for an average of 4 years, with neurological, psychometric, and neuroimaging examinations. Excellent health at entry did not protect against cognitive decline. Incidence of cognitive decline rose sharply with age. epsilon4 and a family history of dementia (independent of epsilon4) were associated with an earlier age at onset of dementia. Subjects who had epsilon4 or a family history of dementia had a ninefold-higher age-specific risk for dementia than did those who had neither epsilon4 nor a family history of dementia. These observations suggest that the rate of cognitive decline increases with age and that APOE and other familial/genetic factors influence the onset age throughout life.     

Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population

Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all‐cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non‐APOE variants. During a median 4.5 years of follow‐up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3‐fold increased dementia risk and 1.4/1.8‐fold cognitive decline risk, versus ε3/ε3 (p < 0.001 for both). High PRS tertile was associated with a 1.4‐fold dementia risk versus low (CI 1.04–1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96–1.22, p = 0.18). Incidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.     

Multi factorial interactions in the pathogenesis pathway of Alzheimer’s disease: a new risk charts for prevention of dementia

Background

The population longitudinal study named “The Conselice Study” has been the focus of the present investigation. 65 years old or older participants of this population study on brain aging were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 46 genetic, phenotypic, clinical and nutritional factors on incident cognitive decline and incident dementia cases were investigated.

Results

A new statistical approach, called the Auto Contractive Map (AutoCM) was applied to find relationship between variables and a possible hierarchy in the relevance of each variable with incident dementia. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Moreover, few variables resulted to be aggregation points in the variable connectivity map related to cognitive decline and dementia. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. A risk map for age associated cognitive decline and dementia has been constructed and will be presented and discussed.

Conclusion

This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia.

     

城市人群血清营养水平指标与膳食习惯关系的分析

目的:分析血清营养状态指标与膳食习惯的关联关系与意义。方法:采用横断面调查的数据,用标准问卷询问1694人相关信息,内容包括人口学资料、自报疾病现患史、膳食习惯、健康自评、认知功能信息;同时采集被调查人群血样本;测定血红蛋白、白蛋白、叶酸和维生素B12水平。采用R 3.2.5和SPSS 20.0软件进行相关和显著性差异分析。结果:人体血红蛋白、白蛋白、叶酸和维生素B12水平与被调查个体进食水果和鸡蛋习惯有密切关联;天天进食水果、鸡蛋的个体上述指标水平明显高于不进食此类食物的个体,且血红蛋白、白蛋白水平随增龄下降程度减低;天天进食水果习惯的个体同时具有天天进食蛋、奶、菜习惯;有进食水果习惯的人群表现为受教育程度高;自评健康状态好和相对自报患病率低等特点。结论:合理膳食习惯可保持较高的血营养状态指标水平;且延缓相关指标水平随增龄下降的程度。天天进食水果习惯可被视为合理膳食的指标,为膳食评估提供简易、可行、有效的指标。     

Protection against discrimination in national dementia guideline recommendations: A systematic review

BackgroundNational dementia guidelines provide recommendations about the most effective approaches to diagnosis and interventions. Guidelines can improve care, but some groups such as people with minority characteristics may be disadvantaged if recommended approaches are the same for everyone. It is not known if dementia guidelines address specific needs related to patient characteristics. The objectives of this review are to identify which countries have national guidelines for dementia and synthesise recommendations relating to protected characteristics, as defined in the UK Equality Act 2010: age, disability, gender identity, marriage and civil partnership, pregnancy and maternity, race, religion or belief, sex, and sexual orientation.Methods and findingsWe searched CINAHL, PsycINFO, and Medline databases and the Guideline International Network library from inception to March 4, 2020, for dementia guidelines in any language. We also searched, between April and September 2020, Google and the national health websites of all 196 countries in English and in each country’s official languages. To be included, guidelines had to provide recommendations about dementia, which were expected to be followed by healthcare workers and be approved at a national policy level. We rated quality according to the iCAHE guideline quality checklist. We provide a narrative synthesis of recommendations identified for each protected characteristic, prioritising those from higher-quality guidelines. Forty-six guidelines from 44 countries met our criteria, of which 18 were rated as higher quality. Most guidelines (39/46; 85%) made at least one reference to protected characteristics, and we identified recommendations relating to age, disability, race (or culture, ethnicity, or language), religion, sex, and sexual orientation. Age was the most frequently referenced characteristic (31/46; 67%) followed by race (or culture, ethnicity, or language; 25/46; 54%). Recommendations included specialist investigation and support for younger people affected by dementia and consideration of culture when assessing whether someone had dementia and providing person-centred care. Guidelines recommended considering religion when providing person-centred and end-of-life care. For disability, it was recommended that healthcare workers consider intellectual disability and sensory impairment when assessing for dementia. Most recommendations related to sex recommended not using sex hormones to treat cognitive impairment in men and women. One guideline made one recommendation related to sexual orientation. The main limitation of this study is that we only included national guidelines applicable to a whole country meaning guidelines from countries with differing healthcare systems within the country may have been excluded.ConclusionsNational guidelines for dementia vary in their consideration of protected characteristics. We found that around a fifth of the world’s countries have guidelines for dementia. We have identified areas of good practice that can be considered for future guidelines and suggest that all guidelines provide specific evidence-based recommendations for minority groups with examples of how to implement them. This will promote equity in the care of people affected by dementia and help to ensure that people with protected characteristics also have high-quality clinical services.

Tiffeny James and team investigate which countries have national guidelines for dementia, and synthesise recommendations relating to protected characteristics as defined in the UK Equality Act 2010.     

Factors Associated with Response to Acetylcholinesterase Inhibition in Dementia: A Cohort Study from a Secondary Mental Health Care Case Register in London

Background

Acetylcholinesterase inhibitors (AChEIs) are widely used to delay cognitive decline in Alzheimer''s disease. Observational studies in routine clinical practice have shown cognitive improvement in some groups of patients receiving these agents but longitudinal trajectories before and after AChEI initiation have not previously been considered.

Objectives

To compare trajectories of cognitive function before and after AChEI initiation and investigate predictors of these differences.

Method

A retrospective longitudinal study was constructed using data from 2460 patients who received AChEIs and who had routine data on cognitive function (Mini-Mental State Examination; MMSE) before and after AChEI initiation. Longitudinal MMSE change was modelled using three-piece linear mixed models with the following segments: 0–12 months prior to AChEI initiation, 0–6 months and 6–36 months after initiation.

Results

MMSE decline was reversed (in that the slope was improved by an average 4.2 units per year, 95% CI 3.5–4.8) during the 6-month period following AChEI initiation compared with the slope in the one year period before AChEI initiation. The slope in the period from 6–36 months following AChEI initiation returned to the pre-initiation downward trajectory. The differences in slopes in the 1 year period prior to AChEI initiation and in the 6 months after initiation were smaller among those with higher MMSE scores at the time of AChEI initiation, among those who received a vascular dementia diagnosis at any point, and among those receiving antipsychotic agents.

Conclusion

In this naturalistic observational study, changes in cognitive trajectories around AChEI initiation were similar to those reported in randomised controlled trials. The magnitude of the difference in slopes between the 1 year period prior to AChEI initiation and the 6 month period after AChEI initiation was related to level of cognitive function at treatment initiation, vascular comorbidity and antipsychotic use.     

Periodontitis and Cognitive Decline in Alzheimer’s Disease

Periodontitis is common in the elderly and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer’s disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer’s disease. We aimed to determine if periodontitis in Alzheimer’s disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer’s Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.