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Decreases in cognitive function related to increases in oxidative stress and inflammation occur with ageing. Acknowledging the free radical-quenching activity and anti-inflammatory action of the carotenoid lycopene, the aim of the present review was to assess if there is evidence for a protective relationship between lycopene and maintained cognitive function or between lycopene and development or progression of dementia. A systematic literature search identified five cross-sectional and five longitudinal studies examining these outcomes in relation to circulating or dietary lycopene. Among four studies evaluating relationships between lycopene and maintained cognition, three reported significant positive relationships. Neither of the two studies reporting on relationship between lycopene and development of dementia reported significant results. Of four studies investigating circulating lycopene and pre-existing dementia, only one reported significant associations between lower circulating lycopene and higher rates of Alzheimer's disease mortality. Acknowledging heterogeneity among studies, there is insufficient evidence and a paucity of data to draw firm conclusions or tease apart direct effects of lycopene. Nevertheless, as low circulating lycopene is a predictor of all-cause mortality, further investigation into its relationship with cognitive longevity and dementia-related mortality is warranted.
The purpose of this study was to assess laypersons’ attitudes and completion of advance care planning (ACP) and to examine associations with sociodemographic characteristics and health beliefs on Alzheimer's disease.
A cross-sectional telephone survey was conducted during April and May 2017, with a sample of 514 Israeli adults, aged 18 years and above. A structured, pretested questionnaire assessing participants’ awareness, attitudes, and completion of ACP, as well as health beliefs on Alzheimer's disease (subjective knowledge, susceptibility, and worry), and sociodemographic factors, was used.
Two-fifths of the participants had heard of at least one of the terms: advance directives or durable power of attorney. Overall, participants expressed positive attitudes toward ACP. Results of regression models showed that gender, religiosity, and subjective knowledge of Alzheimer's disease were statistically significant correlates of attitudes toward ACP. Adding health beliefs on Alzheimer's disease doubled the amount of the variance explained, from 3% to 6%.
Significance of results
Our results support the use of cognitive models of health behavior by assessing intra-personal beliefs and knowledge to understand ACP attitudes and completion. Specifically, we demonstrated the importance of knowledge of Alzheimer's disease for ACP attitudes, suggesting the importance of including a module on the topic to ACP interventions.
Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia.
To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease.
A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25–0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale – cognitive subscale) and functional (Clinical Dementia Rating – Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0–48 months).
Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (Aβ1−42) after 36 months.
Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI–Alzheimer's disease continuum.
Many important scientific and technical problems are best addressed using multiple, microscopy-based analytical techniques that combine the strengths of complementary methods. Here, we provide two examples from biomedical challenges: unravelling the attachment zone between dental implants and bone, and uncovering the mechanism of Alzheimer's disease. They combine synchrotron-based scanning transmission X-ray microscopy (STXM) with transmission electron microscopy ((S)TEM), electron tomography (ET), EELS tomography, and/or atom probe tomography (APT). STXM provides X-ray absorption based chemical sensitivity at mesoscale resolution (10–30 nm), which complements higher spatial resolution electron microscopy and APT.
Humans can recollect past events in details (recollection) and/or know that an object, person or place has been encountered before (familiarity). During the last two decades, there has been intense debate about how recollection and familiarity are organized in the brain. Here, we propose an Integrative Memory model which describes the distributed and interactive neurocognitive architecture of representations and operations underlying recollection and familiarity. In this architecture, the subjective experience of recollection and familiarity arises from the interaction between core systems storing particular kinds of representations shaped by specific computational mechanisms and an attribution system. By integrating principles from current theoretical views about memory functioning, we provide a testable framework to refine the prediction of deficient versus preserved mechanisms in memory-impaired populations. The case of Alzheimer's disease is considered as an example because it entails progressive lesions starting with limited damage to core systems before invading step-by-step most parts of the model-related network. We suggest a chronological scheme of cognitive impairments along the course of Alzheimer's disease, where the inaugurating deficit would relate early neurodegeneration of the perirhinal/anterolateral entorhinal cortex to impaired familiarity for items that need to be discriminated as viewpoint-invariant conjunctive entities. The Integrative Memory model can guide future neuropsychological and neuroimaging studies aiming to understand how such a network allows humans to remember past events, to project into the future and possibly also to share experiences.
To identify, review, and critically appraise model-based economic evaluations of all types of interventions for people with dementia and their carers.
A systematic literature search was undertaken to identify model-based evaluations of dementia interventions. A critical appraisal of included studies was carried out using guidance on good practice methods for decision-analytic models in health technology assessment, with a focus on model structure, data, and model consistency.
Interventions for people with dementia and their carers, across prevention, diagnostic, treatment, and disease management.
We identified 67 studies, with 43 evaluating pharmacological products, 19 covering prevention or diagnostic strategies, and 5 studies reporting non-pharmacological interventions. The majority of studies use Markov models with a simple structure to represent dementia symptoms and disease progression. Half of all studies reported taking a societal perspective, with the other half adopting a third-party payer perspective. Most studies follow good practices in modeling, particularly related to the decision problem description, perspective, model structure, and data inputs. Many studies perform poorly in areas related to the reporting of pre-modeling analyses, justifying data inputs, evaluating data quality, considering alternative modeling options, validating models, and assessing uncertainty.
There is a growing literature on the model-based evaluations of interventions for dementia. The literature predominantly reports on pharmaceutical interventions for Alzheimer's disease, but there is a growing literature for dementia prevention and non-pharmacological interventions. Our findings demonstrate that decision-makers need to critically appraise and understand the model-based evaluations and their limitations to ensure they are used, interpreted, and applied appropriately.
Depression and a number of other psychiatric conditions can impair cognition and give the appearance of neurodegenerative disease. Collectively, this group of disorders is known as ‘pseudodementia’ and are important to identify given their potential reversibility with treatment. Despite considerable interest historically, the longitudinal outcomes of patients with pseudodementia remain unclear. We conducted a systematic review of longitudinal studies of pseudodementia. Bibliographic databases were searched using a wide range of search terms. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 18 studies with follow-up varying from several weeks to 18 years. Overall, 284 patients were studied, including 238 patients with depression, 18 with conversion disorder, 14 with psychosis, and 11 with bipolar disorder. Irrespective of diagnosis, 33% developed irreversible dementia at follow-up, 53% no longer met criteria for dementia, and 15% were lost to follow-up. Considerable variability was identified, with younger age at baseline, but not follow-up duration, associated with better outcomes. ECT and pharmacological interventions were also reported to be beneficial, though findings were limited by the poor quality of the studies. Overall, the findings suggest that pseudodementia may confer an increased risk of irreversible dementia in older patients. The findings also indicate, however, that a significant proportion improve, while many remain burdened with their psychiatric condition, independent of organic dementia. The findings support the clinical value of the construct and the need for its re-examination in light of developments in neuroimaging, genomics, other investigative tools, and trial methodology.
Shared decision-making is advocated but may be affected by cognitive impairment. Measures of shared decision-making provide global descriptions of communication without detailed analysis of the subtle ways in which doctors invite patient input.
We aimed to explore medication decisions in dementia, using a standardised Treatment Recommendation Coding Scheme.
We analysed 71 video-recorded dementia diagnostic meetings from nine memory clinics. Recommendations were coded as pronouncements (‘I will start you on medication’), proposals (‘Shall we try medication?’), suggestions (‘Would you like to try medication?’), offers (‘I can prescribe medication’) or assertions (‘There is medication’). Patient responses were coded as acceptance (‘I'd like to have that’), active resistance (‘I'm not very keen’) and passive resistance (minimal or no response). Cognitive test scores, prescription rates and satisfaction were assessed and associations were explored.
Doctors used suggestions in 42% of meetings, proposals in 25%, assertions in 13%, pronouncements in 11% and offers in 9%. Over 80% of patients did not indicate clear acceptance. Patients were most likely to actively resist after suggestions. There was no association between cognitive impairment and recommendation format. Patients were less satisfied with pronouncements. Patient preference did not influence whether medication was prescribed.
Doctors initially nominate people with dementia as the decision maker, and this is unaffected by cognitive impairment. Over 80% of patients resisted starting medication, mostly through passive resistance, the most common form of disagreement in communication. Medication still tended to be prescribed, indicating that factors other than patient preference affect prescription.
The enormous economic burden of dementia in the United States of America falls disproportionately on families coping with this devastating disease. Black Americans, who are at greater risk of developing dementia than white Americans, hold on average less than one-eighth of the wealth of white Americans. This study explores whether dementia exacerbates this wealth disparity by examining dementia's effect on wealth trajectories of black versus non-black Americans over an eight-year period preceding death, using five waves of data (beginning in 2002 or 2004) on decedents in the 2012 and 2014 waves of the Health and Retirement Study (N = 2,429). Dementia is associated with a loss of 97 per cent of wealth among black Americans, compared with 42 per cent among non-black Americans, while wealth loss among black and non-black Americans without dementia did not differ substantially (15% versus 19%). Dementia appears to increase the probability of wealth exhaustion among both black and non-black Americans, although the estimate is no longer significant after adjusting for all covariates (for blacks, odds ratio (OR) = 2.04, 95% confidence interval (CI) = 0.83, 5.00; for non-blacks, OR = 1.47, 95% CI = 0.95, 2.27). Dementia has a negative association with home-ownership, and the loss or sale of a home may play a mediating role in the exhaustion of wealth among black Americans with dementia.
The aim of this study was to update the literature on interventions for carers of people with dementia published between 2006 and 2016 and evaluate the efficacy of psychoeducational programs and psychotherapeutic interventions on key mental health outcomes (depression, anxiety, burden, and quality of life).
A meta-analysis was carried out of randomized controlled trials of carer interventions using MEDLINE, PsycINFO, Scopus, and Cochrane Central Register of Controlled Trials.
The majority of studies were conducted in Western and Southern Europe or the United States and recruited carers of people with Alzheimer's disease or dementia grouped as a whole. The most commonly used outcome measures were depression and burden across studies. The updated evidence suggested that psychoeducation-skill building interventions delivered face-to-face can better impact on burden. Psychotherapeutic interventions underpinned by Cognitive Behavior Therapy (CBT) models demonstrated strong empirical support for treating anxiety and depression and these effects were not affected by the mode of delivery (i.e. face-to-face vs. technology). A modern CBT approach, Acceptance and Commitment Therapy (ACT), seemed to be particularly beneficial for carers experiencing high levels of anxiety.
Future research needs to explore the efficacy of interventions on multiple clinical outcomes and which combination of interventions (components) would have the most significant effects when using CBT. The generalization of treatment effects in different countries and carers of different types of dementia also need to be addressed. More research is needed to test the efficacy of modern forms of CBT, such as ACT.
Since baseline executive dysfunction predicts worsening Instrumental Activities of Daily Living (i-ADL) over time and progression to Alzheimer's Disease (AD), we aimed to analyze the role of neuropsychological variables to outline which factors can contribute to functional impairment. Specific attention to executive functions (EFs) has been given.
A total of 144 subjects complaining of different cognitive deficits – ranging from “MCI likely due to AD” to “mild AD patients” – underwent an overall neuropsychological assessment. The Behavioral Assessment of the Dysexecutive Syndrome was used to analyze EFs. We conducted multiple linear regression analyses to study whether the level of independent living skills – assessed with the Lawton-scale – could be associated with cognitive and behavioral measurements.
We found a significant association between i-ADL and specific EFs measured by Rule Shift Cards (p = 0.04) and Modified Six Elements (p = 0.02). Moreover, considering i-ADL scores, we observed an involvement of mood changes and a reduced awareness of deficits in terms of Hamilton Depression Rating Scale (p = 0.02) and Awareness of Deficit Questionnaire – Dementia scale (p < 0.0001), respectively.
Our results suggest the importance of considering the association between a reduction in i-ADL and executive dysfunction in patients who have AD etiopathology, for which the ability to inhibit a response, self-monitoring, set-shifting and mood deflection play a key role. Besides, no straightforward associations between i-ADL scores and global cognition, memory, language comprehension, attention, and perspective taking abilities were found.
Current policy emphasises the importance of ‘living well’ with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1–0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.
Our study aims to detect different types of response shifts (RS) and true changes of quality of life (QOL) measurement in patients with Alzheimer's disease (AD) using structural equation modeling (SEM) in domain level.
Patients with AD aged over 60 years old were collected from the Department of Neurology and Geriatrics in Taiyuan Central Hospital, China. The 12-item Short Form (SF-12) Health Survey was measured in 238 patients with AD prior to hospitalization and one month following discharge. RS was detected by SEM approach. The statistical process consisted of four steps and fitted four models. We interpreted changes of parameters in models to detect RS and to assess true change.
The results showed reprioritization of social functioning (SF) (χ2 = 4.13, p < 0.05), reconceptualization of role limitations due to emotional problems (RE) (χ2 = 17.03, p < 0.001), uniform recalibration of bodily pain (BP) (χ2 = 12.24, p < 0.001), and non-uniform recalibration of mental health (MH) (χ2 = 4.41, p < 0.05), respectively. The true changes of common factors were deteriorated in general physical health (PHYS) (−0.10, χ2 = 8.30, p < 0.005) and improved in general mental health (MENT) (+0.29, χ2 = 20.95, p < 0.001). The effect-sizes of RS were only small.
This study showed that patients with AD occurred three types of RS and true changes one month following discharge. RS had effects on the QOL of patients. Better understanding of potential changes in QOL in patients with AD is crucial.
The primary objective of this study was to determine whether a brief education session about Alzheimer's disease (AD) stages and associated behavioral and psychological symptoms of dementia (BPSD) changes healthy seniors’ treatment choices. A secondary objective was to determine whether pharmacotherapy to reduce BPSD would be preferred over other potentially more restrictive interventions.
Participants (n = 32; 8 men; aged > 64years; no self-reported dementia diagnosis) were assigned to one of ten group sessions during which they received information about AD and BPSD. Our a-priori hypotheses were: (1) education about AD stages significantly changes care preferences in moderate and severe stages, i.e. less active treatment options (no CPR/hospitalization) are chosen as the disease progresses; and (2) most participants prefer pharmacotherapy over restraints and seclusion to manage BPSD. The main outcome measure was a change in the interventions chosen including CPR and hospitalization. Participants completed three questionnaires and two decisional grids before and after the information session. Qualitative data were derived from discussions during the session.
Participants expressed a wide range of attitudes about AD, BPSD, and their management. Those who are born in Canada, had a proxy, and a university education, each have around half of the odds of receiving treatment compared to those in the complementary group. (OR 0.47, 0.40, 0.43) Finally, not knowing someone with AD increases the odds of wanting a treatment by around six times (OR 6.4). Pharmacological measures were preferred over restraints.
Education about dementia and advance directives should consider the person's educational background and experience with dementia. Discussing BPSD may impact a person's advance directives and preferences.
Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967–973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline.
Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years. Setting: Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin.
For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and were native English speakers.
Memory data were collected using the Rey's Auditory Verbal Learning Test, and the early MCI diagnosis was obtained via consensus conference.
Our results showed that higher Rr scores are correlated with greater risk of later early MCI diagnosis, and this association is independent of total recall performance.
Rr is an emerging cognitive marker of cognitive decline.
Longitudinal studies of older adults are characterized by high dropout rates, multimorbid conditions, and multiple medication use, especially proximal to death. We studied the association between multiple medication use and incident dementia diagnoses including Alzheimer's disease (AD), vascular dementia (VD), and Lewy-body dementia (LBD), simultaneously accounting for dropout.
Using the National Alzheimer's Coordinating Center data with three years of follow-up, a set of covariate-adjusted models that ignore dropout was fit to complete-case data, and to the whole-cohort data. Additionally, covariate-adjusted joint models with shared random effects accounting for dropout were fit to the whole-cohort data. Multiple medication use was defined as polypharmacy (⩾ five medications), hyperpolypharmacy (⩾ ten medications), and total number of medications.
Incident diagnoses were 2,032 for AD, 135 for VD, and 139 for LBD. Percentages of dropout at the end of follow-up were as follows: 71.8% for AD, 81.5% for VD, and 77.7% for LBD. The odds ratio (OR) estimate for hyperpolypharmacy among those with LBD versus AD was 2.19 (0.78, 6.15) when estimated using complete-case data and 3.00 (1.66, 5.40) using whole-cohort data. The OR reduced to 1.41 (0.76, 2.64) when estimated from the joint model accounting for dropout. The OR for polypharmacy using complete-case data differed from the estimates using whole-cohort data. The OR for dementia diagnoses on total number of medications was similar, but non-significant when estimated using complete-case data.
Reasons for dropout should be investigated and appropriate statistical methods should be applied to reduce bias in longitudinal studies among high-risk dementia cohorts.
Caring for persons with dementia (PWD) can create “caregiver burden,” which is associated with negative outcomes for caregivers and PWD. The ZBI (Zarit Burden Interview) is a widely used unitary measure of caregiver burden. However, recent research has found caregiver burden to be multi-dimensional. The purpose of this study was to explore the factor structure of the ZBI within a sample of UK caregivers. A secondary aim was to identify variables that predicted burden dimensions found.
A total of 110 unpaid community caregivers of PWD completed the ZBI. They also completed the EACQ (Experiential Avoidance in Caregiving Questionnaire), DEX (Dysexecutive Questionnaire), PACS (Positive Aspects of Caregiving Scale), and a demographic questionnaire. ZBI data were analyzed via exploratory factor analysis (principal axis factoring). Relationships between burden factors and other variables were studied using Pearson correlations and multiple regression.
Analysis identified three burden factors, namely direct impact of caregiving, uncertainty around the future, and frustration/embarrassment. A direct impact of caregiving and frustration/embarrassment has been found previously. Uncertainty over the future is a new factor, which was predicted by adult-child caregiver role, highlighting that spouses and adult children are likely to have different burden experiences. Additionally, uncertainty over the future and frustration/embarrassment were inversely predicted by PACS, suggesting that being mindful of positive aspects of caregiving may function as a protective factor for burden.
This study found caregiver burden to be multi-dimensional and uncovered a novel factor in uncertainty over the future, which warrants further exploration. Burden factors were associated with a range of modifiable variables that could be targeted within health and social care interventions to improve outcomes for caregivers and PWD.
The use of FDA approved medications for Alzheimer's disease [AD; FDAAMAD; (cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists)] has been associated with symptomatic benefit with a reduction in formal (paid services) and total costs of care (formal and informal costs). We examined the use of these medications and their association with informal costs in persons with dementia.
Two hundred eighty participants (53% female, 72% AD) from the longitudinal, population-based Dementia Progression Study in Cache County, Utah (USA) were followed up to ten years. Mean (SD) age at baseline was 85.6 (5.5) years. Informal costs (expressed in 2015 dollars) were calculated using the replacement cost method (hours of care multiplied by the median wage in Utah in the visit year) and adjusted for inflation using the Medical Consumer Price Index. Generalized Estimating Equations with a gamma log-link function were used to examine the longitudinal association between use of FDAAMAD and informal costs.
The daily informal cost for each participant at baseline ranged from $0 to $318.12, with the sample median of $9.40. Within the entire sample, use of FDAAMAD was not significantly associated with informal costs (expβ = 0.73, p = 0.060). In analyses restricted to participants with mild dementia at baseline (N = 222), use of FDAAMAD was associated with 32% lower costs (expβ = 0.68, p = 0.038).
Use of FDAAMAD was associated with lower informal care costs in those with mild dementia only.
We analyzed the impact of opioid initiation on the prevalence of antipsychotic and benzodiazepine and related drug (BZDR) use among community-dwelling persons with Alzheimer's disease (AD).
We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010–2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later.
Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1–0.5) and 0.4 pps (0.2–0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9–2.8) for antipsychotics and of 1.6 pps (0.9–2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3–0.8) per month for antipsychotics and of 0.4 pps (0.2–0.6) for BZDR use until the end of the follow-up.
Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.