Despite decades of research in the field of Alzheimer's disease (AD), a real understanding of its molecular pathophysiology and treatments relevant to the day-to-day lives of patients remain out of reach. Research has, with good reason, focused on certain key pathways and potential mechanisms, but sometimes this has been at the expense of work on other theories, which may be slowing down progress in this field. Interesting theories at present include oxidative stress and caloric restriction. Work on the Aβ cascade should continue but with a shift in focus to its intracellular effects and an awareness that additional pathogenetic factors and processes must be involved – most importantly, brain aging. Hyperphosphorylation of tau, for instance, provides another interesting pathway, with one old drug showing promise in this regard. Moreover, work in epigenetics and on protein homeostasis has produced interesting findings and both lines of investigation may reveal suitable targets for future intervention. Taken together, analysis of the biochemistry of aged neurons and the interplay with pathways of neurodegeneration may lead to a better understanding of AD and how to treat and prevent this condition.

Background: People with dementia report lower quality of life, but we know little about what interventions might improve it.

Methods: We systematically reviewed 20 randomized controlled trials reporting the effectiveness of non-pharmacological interventions in improving quality of life or well-being of people with dementia meeting predetermined criteria. We rated study validity with a checklist. We contacted authors for additional data. We calculated standardized mean differences (SMD) and, for studies reporting similar interventions, pooled standardized effect sizes (SES).

Results: Pooled analyses found that family carer coping strategy-based interventions (four studies, which did not individually achieve significance; n = 420; SES 0.24 (range 0.03–0.45)) and combined patient activity and family carer coping interventions (two studies, not individually significant; n = 191; SES 0.84 (range 0.54–1.14)) might improve quality of life. In one high-quality study, a care management system improved quality of life of people with dementia living at home. Group Cognitive Stimulation Therapy (GCST) improved quality of life of people with dementia in care homes.

Conclusion: Preliminary evidence indicated that coping strategy-based family carer therapy with or without a patient activity intervention improved quality of life of people with dementia living at home. GCST was the only effective intervention in a higher quality trial for those in care homes, but we did not find such evidence in the community. Few studies explored whether effects continued after the intervention stopped. Future research should explore the longer-term impact of interventions on, and devise strategies to increase, life quality of people with dementia living in care homes or at home without a family carer.

Background: Behavioral and psychological symptoms of dementia (BPSDs) are routinely cited as important predictors of caregiver burden and depression. Although BPSDs include a wide variety of patient behaviors, they are routinely grouped together as one construct to differentiate them from cognitive symptoms of dementia. Determining the specific BPSDs that result in increased depression and burden for caregivers may elucidate the stress process for caregivers and facilitate the development of effective interventions for caregivers.

Methods: We conducted a systematic review of English-language articles published from 1990 to 2010 to determine whether there are known symptoms or symptom clusters which exert undue negative impact on caregiver depression and burden. Additionally, we review systems used for classifying BSPD symptom clusters and determine whether there have been any mechanisms studied by which individual BPSD symptoms negatively affect caregivers. Finally, we examine how the role of timing of symptoms has been examined within the literature.

Results: Thirty-five original research articles examined the impact of an individual behavior symptom on caregiver burden or depression/depressive symptoms. The studies had no consistent system for categorizing symptoms. Although depression, aggression, and sleep disturbances were the most frequently identified patient symptoms to impact negatively on caregivers, a wide range of symptoms was associated with caregiver burden and depression.

Conclusions: The evidence is not conclusive as to whether some symptoms are more important than others. The studies reviewed were largely exploratory relative to the differential impact of individual BPSDs and did not focus on testing causal mechanisms by which specific symptoms exert more impact on caregiver mental health than others. Future research may benefit from the re-conceptualization of BPSDs from the perspective of their impact on the caregiver to examine hypothesis-driven differences among BPSD symptom clusters.

Background: Admission to a nursing home might challenge the way in which individuals experience their own sexuality, but it does not automatically diminish their need and desire for sexual fulfillment. Despite the fact that sexuality proves to be an intrinsic part of human existence, the sexual expression of geriatric residents remains a sensitive subject for many caregivers and family members. It evokes a variety of ethical issues and concerns, especially when dementia patients are involved. The overall objective of this review was to examine the ethical arguments and concepts about the debate on sexuality within a nursing home environment.

Methods: We conducted a systematic search for argument-based ethics literature focusing on sexuality in institutionalized elderly people. Twenty-five appropriate studies were identified.

Results: A thematic analysis of the included literature led us to distinguish two major groups of ethical arguments: (i) principles and (ii) care. Ethics arguments on sexuality in institutionalized elderly are particularly guided by the principle of respect for autonomy and the concomitant notion of informed consent. Arguments related to care were also apparent within the research literature although they received considerably less attention than the arguments related to the principles of respect for autonomy, beneficence, nonmaleficence and justice.

Conclusions: The lack of clarity in the conceptualization of the arguments referred to in the research literature indicates that there is a pressing need for a better defined, more fundamental philosophical-ethical analysis of the values at stake.

Background: The use of telemedicine for the care of mental health problems has developed significantly over the last decade thanks to the emergence of a number of stable telepsychiatry programs in many countries. Parallel to this development, this care modality has also targeted specific populations with higher difficulty in gaining access to mental health services such as the elderly. Telepsychogeriatrics is expected to have an increasing role in providing care to geographically isolated rural communities, with a particular focus on long-term care facilities, in light of the high prevalence of psychiatric disorders in these centers and the lack of available specialized care.

Methods: A thorough search of the literature was conducted using Medline, Web of Science, and PsychINFO databases in order to gather available evidence on the applicability of telepsychiatry, specifically the use of videoconferencing for remote consultation, in the elderly population with mental disorders. A succinct description of the selected studies is given along with a general reflection on the state-of-the-art in the field of psychogeriatric clinical practice and research.

Results: Research on the use of telemedicine in this age group has taken into account their special characteristics, and has focused on demonstrating its applicability, the acceptance and satisfaction of elderly users and their healthcare providers, the possibility of carrying out cognitive and diagnostic assessments, and the efficiency of these programs.

Conclusions: Despite limited experience, telepsychogeriatrics appears to be a viable option, well accepted by patients, including those having dementia. More systematized studies are needed in this new field based on larger sample sizes, including comparison with traditional consultations and assessment of the clinical outcomes.

Background: Dementia places a huge demand on healthcare services; however, a large proportion of the cost is borne by informal caregivers. With the number of people affected by dementia set to increase in the future, there is a need for research to consider the effects of interventions on informal caregivers as well as on the individuals with dementia. This paper seeks to systematically review the existing evidence on the cost-effectiveness of interventions to support informal caregivers of people with dementia residing in the community.

Methods: A range of electronic databases was searched. Studies were included if both costs and outcome measures for informal caregivers of people with dementia residing in the community were reported for an intervention. Both pharmacological and non-pharmacological interventions were included. Quality of study was assessed using the Drummond ten-item checklist for economic evaluations and results were presented through narrative synthesis.

Results: Twelve studies were included in the review; of these only four reported a significant difference in the outcome measure for caregivers.

Conclusions: At present few published studies report costs in enough detail to provide evidence of the effectiveness and cost-effectiveness of interventions for supporting caregivers. Future trials need to collect caregiver data alongside patient data in order to increase the evidence base for intervention effectiveness. Further research is required to establish the effectiveness and cost-effectiveness of both pharmacological and non-pharmacological approaches.

Background: Cardiovascular risk factors and diseases are important etiological factors in depression, particularly late-life depression. Brain changes associated with vascular disease and depression can be detected using magnetic resonance imaging. Using diffusion tensor imaging (DTI), we investigated whether the Framingham Stroke Risk Profile (FSRP), a well-validated risk prediction algorithm, is associated with changes in white-matter connectivity. We hypothesized that depressed participants would show reduced white-matter integrity with higher FSRP, and non-depressed controls (matched for mean vascular risk) would show minimal co-variance with white-matter changes.

Methods: Thirty-six participants with major depression (age 71.8 ± 7.7 years, mean FSRP 10.3 ± 7.6) and 25 controls (age 71.8 ± 7.3 years, mean FSRP 10.1 ± 7.7) were clinically interviewed and examined, followed by 60-direction DTI on a 3.0 Tesla scanner. Image analysis was performed using FSL tools (www.fmrib.ox.ac.uk/fsl) to assess the correlation between FSRP and fractional anisotropy (FA). Voxelwise statistical analysis of the FA data was carried out using Tract Based Spatial Statistics. The significance threshold for correlations was set at p < 0.05 using threshold-free cluster-enhancement. Partial correlation analysis investigated significant correlations in each group.

Results: Participants in the depressed group showed highly significant correlations between FSRP and FA within the body of corpus callosum (r = −0.520, p = 0.002), genu of corpus callosum (r = −0.468, p = 0.005), splenium of corpus callosum (r = −0.536, p = 0.001), and cortico-spinal tract (r = −0.473, p = 0.005). In controls, there was only one significant correlation in the body of corpus callosum (r = −0.473, p = 0.023).

Conclusions: FSRP is associated with impairment in white-matter integrity in participants with depression; these results suggest support for the vascular depression hypothesis.

Background: Frailty in older adults is a multifactorial syndrome defined by low metabolic reserve, less resistance to stressors, and difficulty in maintaining organic homeostasis due to cumulative decline of multiple physiological systems. The relationship between frailty and cognition remains unclear and studies about Mini-Mental State Examination (MMSE) performance and frailty are scarce. The objective was to examine the association between frailty and cognitive functioning as assessed by the MMSE and its subdomains.

Methods: A cross-sectional population-based study (FIBRA) was carried out in Ermelino Matarazzo, a poor subdistrict of the city of São Paulo, Brazil. Participants were 384 community dwelling older adults, 65 years and older who completed the MMSE and a protocol to assess frailty criteria as described in the Cardiovascular Health Study (CHS).

Results: Frail older adults had significantly worse performance on the MMSE (p < 0.001 for total score). Linear regression analyses showed that the MMSE total score was influenced by age (p < 0.001), education (p < 0.001), family income (p < 0.001), and frailty status (p < 0.036). Being frail was associated more significantly with worse scores in Time Orientation (p < 0.004) and Immediate Memory (p < 0.001).

Conclusions: Our data suggest that being frail is associated with worse cognitive performance, as assessed by the MMSE. It is recommended that the assessment of frail older adults should include the investigation of their cognitive status.

Background: Life expectancy with dementia directly influences rates of prevalence and service needs and is a common question posed by families and patients. As well as years of survival, it is useful to consider years of life lost after a diagnosis of dementia.

Methods: We systematically reviewed the literature on mortality and survival with dementia which were compared to estimated life expectancies in the general population. Both were then compared by age (under 65 years vs. 65+ years), gender, dementia type, severity, and two epochs (prior to and after introduction of cholinesterase inhibitors in 1997).

Results: Survival after a diagnosis of dementia varies considerably and depends on numerous factors and their complex interaction. Relative loss of life expectancy decreases with age at diagnosis across varying gender, dementia subtypes (except for frontotemporal dementia and dementia with Lewy bodies), and severity stages. Numerous study deficiencies precluded a meta-analysis of survival in dementia.

Conclusion: Estimates of years of life lost through dementia may be helpful for patients and their families. Recommendations for future research methods are proposed.

Background: Mild cognitive impairment (MCI) is a relatively common condition and rates of diagnosis are likely to increase in the near future. Little is known about the experiences of patients with MCI and their carers nor about the most appropriate interventions to support this group.

Methods: The existing literature on this topic up to July 2011 was identified via systematic searches of the Embase and Medline databases, the Cochrane Library and relevant sections of the National Electronic Library for Health. The main search term “mild cognitive impairment” was used in combination with other relevant terms. The reference lists of reviewed articles were also examined for any additional papers of significance. Papers identified by this method were examined and those deemed relevant were included in this review.

Results: Twenty-one suitable papers were identified for inclusion in this review, a relatively small number. The studies reviewed suggest that patients with MCI and their carers face a variety of practical and emotional challenges. No interventional studies of support have been undertaken, but the authors of relevant observational studies have suggested provision of information, psychosocial support and strategies to enhance patient interaction with carers and social contacts.

Conclusions: MCI results in significant challenges for both patients and their carers. Further work is required in order to establish the best way to help patients and carers meet these challenges.

Background: Problems with out-of-home mobility are among the more common behavioral disturbances in dementia. Today people with dementia can be aided by easily accessible assistive technologies, such as tracking devices using Global Positioning Systems (GPS). Attitudes toward these technologies are still inconclusive and their use with people with dementia raises ethical concerns. The lack of ethical consensus on the use of GPS for people with dementia underlines the need for clearer policies and practical guidelines.

Methods: Here we summarize qualitative and quantitative findings from a larger research project on the ethical aspects of using GPS for tracking people with dementia.

Results: The findings are formulated in a list of recommendations for policy-makers as well as for professional and family caregivers. Among other points, the recommendations indicate that the preferences and best interests of the people with dementia should be central to the difficult decisions required in dementia care. Further, no-one should be coerced into using tracking technology and, where possible, people with dementia must be involved in the decision-making and their consent sought.

Conclusions: The decision whether, when and how to use GPS for tracking people with dementia should be made at the time of diagnosis jointly by the person with dementia, his/her family and professional caregivers. This decision should be made in formal structured meetings facilitated by a professional team.

Background: Certain risk factors for cognitive decline appear modifiable. A potentially modifiable marker of inflammation, C-reactive protein may be associated with cognitive deficits, although not all studies have found a relationship between C-reactive protein and cognitive ability. Further, few research papers have examined whether gender may affect any association between C-reactive protein and cognitive deficit.

Methods: To better understand the association between C-reactive protein, cognitive deficit, and gender in elderly people, we meta-analyzed cross-sectional studies that reported cognitive ability assessed by the Mini-Mental State Examination or an equivalent measure, C-reactive protein concentrations, and gender.

Results: While we identified no studies containing only male subjects, the two identified studies containing both female and male subjects (n = 2,525) showed an effect size for cognition of −0.1809 (95% confidence interval, −0.2652 to −0.0967, p = 0.000025) between high and low C-reactive-protein groups. In contrast, the two identified studies containing only female subjects (n = 1,754) showed an effect size for cognition of 0.0345 (95% confidence interval, −0.0594 to 0.1285, not significant).

Conclusions: In the context of a small number of source studies and lack of an all-male group, these results suggest that any association between C-reactive protein and cognitive deficits may be stronger in elderly men than in elderly women.

The development of therapies for Alzheimer's disease (AD) presents numerous challenges for physicians, researchers, and the pharmaceutical industry, with many drug candidates showing promise at one stage of clinical research only to fall at the next hurdle. A great number of drugs with a variety of targets and clusters of mechanisms are currently in various stages of basic and clinical investigation. However, these hypothesis-derived agents may be tested much too late in the chronically progressive disease process to demonstrate meaningful effects or outcomes, mirroring the clinical syndromal scenario in which the underlying pathophysiological disease condition is frequently diagnosed extremely late. Moreover, the complexity of the disease calls for developments and improvements in study designs and methods modeled for different target populations and disease stages (e.g. asymptomatic to prodromal to syndromal). New integrated concepts and models of disease pathophysiology, use of validated and qualified biomarkers, outcomes and endpoints, particularly the development of a surrogate outcome, may allow targeting of characteristic mechanism-derived therapies of specifically affected biological systems at different time-points in the disease process, providing increasing opportunities for early and preventative intervention. A core set of feasible diagnostic and predictive biomarkers is already validated and in the process of standardization; however, continued and intensified research efforts will likely reveal a variety of novel biomarkers that grasp the complexity of the underlying disease process. In the future, trials of drugs to modify and prevent AD may embrace enrichment strategies and maybe be stratified by disease stage, genetic factors as well as by disease endophenotypes.

Background: There is growing evidence that neighborhood environments are related to depressive mood in the general population. Older adults may be even more vulnerable to neighborhood factors than other adults. The aim of this paper is to review empirical findings on the relationships between neighborhood characteristics and depressive mood among older adults.

Methods: A search of the literature was undertaken in PsycINFO and MEDLINE.

Results: Nineteen studies were identified. Study designs were most often cross-sectional, included large sample sizes, and controlled for major individual characteristics. Mediational effects were not investigated. Statistical analysis strategies often included multilevel models. Spatial delimitations of neighborhood of residence were usually based on administrative and statistical spatial boundaries. Six neighborhood characteristics were assessed most often: neighborhood socioeconomic disadvantage, neighborhood poverty, affluence, racial/ethnic composition, residential stability, and elderly concentration. Selected neighborhood characteristics were associated with depressive mood after adjusting for individual variables. These associations were generally theoretically meaningful.

Conclusions: Neighborhood variables seem to make a unique and significant contribution to the understanding of depressive mood among older adults. However, few studies investigated these associations and replication of results is needed. Several substantive neighborhood variables have been ignored or neglected in the literature. The implications of neighborhood effects for knowledge advancement and public health interventions remain unclear. Recommendations for future research are discussed.

Background: There are a number of models of patient and carer participation. Their usefulness and applicability to old age psychiatry is considered.

Methods: Models of participation are reviewed and related to examples of participation initiatives drawn from the author's work in the context of the National Health Service in the United Kingdom.

Results: Models of participation which emphasize collaboration and partnership are found to be useful. Simple interventions such as copying letters to patients and/or carers can lead to change in the balance of power between staff and patients/carers. Initiatives which draw on the experiences of patients and carers can facilitate organizational learning and development. Involving patients and carers in education offers a way to influence services and the staff working in them.

Conclusion: Participation is better understood as a spectrum rather than a hierarchy. Old age psychiatry services would benefit from developing greater patient and carer participation at all levels.

Background: Many studies have investigated factors associated with the rate of decline and evolution from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia in elderly patients. In this analysis, we compared the rates of decline to dementia estimated from three common global measures of cognition: Mini-Mental State Examination (MMSE) score, Clinical Dementia Rating sum of boxes (CDR-SB) score, and a neuropsychological tests composite score (CS).

Methods: A total of 2,899 subjects in the National Alzheimer's Coordinating Center Uniform Data Set aged 65+ years diagnosed with amnestic mild cognitive impairment (aMCI) were included in this analysis. Population-averaged decline to dementia rates was estimated and compared for standardized MMSE, CDR-SB, and CS using Generalized Estimating Equations (GEE). Associations between rate of decline and several potential correlates of decline were also calculated and compared across measures.

Results: The CDR-SB had the steepest estimated slope, with a decline of 0.49 standard deviations (SD) per year, followed by the MMSE with 0.22 SD per year, and finally the CS with 0.07 SD per year. The rate of decline of the three measures differed significantly in a global test for differences (p < 0.0001). Age at visit, body mass index (BMI) at visit, Apolipoprotein E (APOE) ɛ4 allele status, and race (black vs. white) had significantly different relationships with rate of decline in a global test for difference among the three measures.

Conclusions: These results suggest that both the rate of decline and the effects of AD risk factors on decline to dementia can vary depending on the evaluative measure used.

Background: Single-volume proton magnetic resonance spectroscopy (1H MRS) has considerable diagnostic potential for Alzheimer's disease (AD). This study investigated 1H MRS in specific regions of the brain, the posterior cingulate gyri (PCG) and the hippocampus, in patients with AD, amnestic mild cognitive impairment (aMCI), and in normal control subjects.

Methods:1H MRS analysis was carried out on 47 patients with AD, 32 patients with aMCI and 56 normal control subjects (NC group). Volumes of the PCG and hippocampus were assessed, and the metabolic signals of N-acetylaspartate (NAA), choline compounds (Cho), myo-inositol (mI), and creatine (Cr) were quantified.

Results: In the PCG, differences between the test groups were found in NAA/Cr, Cho/Cr, mI/Cr and NAA/mI ratios. Group differences were also found in mI/Cr and NAA/mI ratios in the left hippocampus, and in mI/Cr and NAA/mI ratios in the right hippocampus. NAA/Cr ratios increased in the PCG between AD and aMCI patients, and between aMCI and NC patients. Conversely, mI/Cr ratios in the PCG and left hippocampus decreased across AD, aMCI, and NC subjects. In discriminate and ROC (Receiver Operating Characteristic) analyses, a NAA/Cr ratio of ≤ 1.50 in the PCG indicated optimal potential for discriminating between aMCI patients and normal control subjects. Discriminating potential was also found to be high for a NAA/mI ratio in the PCG of ≤ 2.72. Despite significant differences between NC and aMCI patients in the mI/Cr ratio in the PCG and in the NAA/mI ratio in the left hippocampus, their sensitivity and specificity were all lower than 75%.

Conclusion: Proton MRS of the PCG using the NAA/Cr ratio as a metabolic marker indicates considerable potential for distinguishing between aMCI and NC subjects.

Background: In randomized clinical trials, adverse events (AEs) are reported for the drug under evaluation and compared with the placebo group. Patients who receive placebo treatment report a high frequency of AEs, but little is understood about the nature of these. No study has yet analyzed the level of cognitive impairment as a crucial aspect for the AEs reported by patients.

Methods: The rates of AEs reported by patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the placebo arms of donepezil trials were compared using a systematic review approach. PubMed was searched with the terms “MCI and donepezil” as well as “AD and donepezil” from January 1989 to December 2010. Nineteen studies fulfilled the selection criteria (3 MCI, n = 783; 16 AD, n = 2,059).

Results: An overall comparison of 81 categories of AEs in the placebo arm of MCI versus AD trials showed that patients in AD trials experienced a significantly higher number of AEs than patients in MCI trials (p < 0.001).

Conclusions: This is the first study showing that AD patients may be at a greater risk of developing AEs than MCI patients. This may be related to a greater presence of somatic comorbidity predisposing them to express emotional distress as physical symptoms and/or to AD patients being frailer and therefore more susceptible to AEs. The phenomena we observed may be interpreted in terms of the “nocebo effect”.

Background: Challenging behaviors such as aggression, screaming, and apathy are often encountered when caring for people with dementia in nursing homes. In this context, a case conference is often recommended for healthcare professionals as an effective instrument to improve the quality of care. However, the subject case conference has not had great consideration in scientific literature. The aim of this review is to describe the effects of case conferences on people with dementia and challenging behavior and the staff in nursing homes.

Methods: A search of intervention studies in nursing homes in the German or English language was performed in the following databases: Medline, Cinahl, PsycINFO, Cochrane library, Embase, and Google Scholar. The selection and the methodological quality of the studies were assessed independently by two authors. The results were summarized and compared based on categories such as study quality or outcomes.

Results: Seven of 432 studies were included in the review. A total of four of seven studies showed a reduction in the challenging behavior of people with dementia, and five showed an influence on the competence, attitudes, and job satisfaction of the staff. However, due to the middle-range quality of several studies, the methodological heterogeneity and differences in the interventions, the results must be interpreted with caution.

Conclusions: In summary, little evidence exists for the positive effects of case conferences in the care of people with dementia. This review highlights the need for methodologically well-designed intervention studies to provide conclusive evidence of the effects of case conferences.

Background: Dementia with Lewy bodies (DLB) is a common form of dementia characterized by visual hallucinations, cognitive fluctuation and parkinsonism. We aimed to compare the patterns of gray matter atrophy in DLB with those in Alzheimer's disease (AD) and normal aging, and to investigate the relationship between atrophy and cognitive measures.

Methods: We used voxel-based morphometry (VBM) to investigate gray matter (GM) loss in DLB (n = 35; mean age = 78.4; MMSE = 20.3), AD (n = 36; mean age = 78.3; MMSE = 19.5) and similar aged controls (n = 35; mean age = 76.7; MMSE = 29.1). T1 weighted MRI scans were acquired at 3 Tesla from all subjects and analyzed using VBM-DARTEL in SPM8. Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG).

Results: We found reduced gray matter in temporal, parietal, occipital, and subcortical structures in DLB when compared to normal controls. The degree of atrophy was less than that observed in AD. There was significantly more medial temporal lobe atrophy in the AD group when compared with DLB. We did not find a correlation between total CAMCOG score and atrophy, but the CAMCOG memory subscale score correlated with temporal lobe atrophy in both the DLB and combined DLB/AD group.

Conclusions: DLB is associated with less gray matter atrophy and relative preservation of the medial temporal lobe when compared to AD. Degree of medial temporal atrophy may be a useful imaging biomarker and our results provide support for its inclusion in the revised consensus criteria for DLB.