Cognitive decline has commonly been considered an inevitable result of brain aging and has been of clinical interest principally because of related difficulties with everyday functioning. Since the 1990s the “normality” of age-related cognitive decline has been called into question, being commonly attributed to a number of underlying disorders. Numerous concepts have been proposed which link subclinical cognitive change to pathological states (mild cognitive disorder, mild neurocognitive disorder, mild cognitive impairment). Of these, mild cognitive impairment (MCI) has become the most popular, driven on the one hand by industrial interests seeking to extend new dementia treatments for a more prevalent subclinical syndrome, and on the other by researchers attempting to identify at-risk populations. MCI has been both criticized for “medicalizing” behavior still within normal limits (Stephan et al., 2008; Moreira et al., 2008) and welcomed in that it suggests cognitive decline with aging may not be inevitable, but rather due to abnormalities which could ultimately be treated. Recently, in both Europe (DuBois et al., 2007) and the USA (Albert et al., 2011), panels of experts have scrutinized the concept of MCI and more broadly the pre-dementia stages of neurodegenerative diseases and offered new research diagnostic criteria. These proposed criteria have highlighted the (potential) value of biomarkers in assisting diagnosis, although some have considered the elevation of biomarkers to this level of importance in diagnosing disease before dementia develops to be premature given both the extent and quality of diagnostic biomarker data currently available (McShane et al., 2011a; 2011b).

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: 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: Early detection of dementia will be important for implementation of disease-modifying treatments in the near future. We aimed to investigate the diagnostic validity and reliability of the Japanese version of the revised Addenbrooke's Cognitive Examination (ACE-R J) for identifying mild cognitive impairment (MCI) and dementia.

Methods: We translated and adapted the original ACE-R for use with a Japanese population. Standard tests for evaluating cognitive decline and dementing disorders were applied. A total of 242 subjects (controls = 73, MCI = 39, dementia = 130) participated in this study.

Results: The optimal cut-off scores of ACE-R J for detecting MCI and dementia were 88/89 (sensitivity 0.87, specificity 0.92) and 82/83 (sensitivity 0.99, specificity 0.99) respectively. ACE-R J was superior to the Mini-Mental State Examination in the detection of MCI (area under the curve (AUC): 0.952 vs. 0.868), while the accuracy of the two instruments did not differ significantly in identifying dementia (AUC: 0.999 vs. 0.993). The inter-rater reliability (ICC = 0.999), test-retest reliability (ICC = 0.883), and internal consistency (Cronbach's α = 0.903) of ACE-R J were excellent.

Conclusion: ACE-R J proved to be an accurate cognitive instrument for detecting MCI and mild dementia. Further neuropsychological evaluation is required for the differential diagnosis of dementia subtypes.

Background: Congestive heart failure (CHF) has been associated with impaired cognitive function, but it is unclear if these changes are specific to CHF and if they get worse with time. We designed this study to determine if adults with CHF show evidence of cognitive decline compared with adults with and without coronary artery disease (CAD).

Methods: A longitudinal study was carried out of 77 adults with CHF (ejection fraction, EF < 0.4), 73 adults with a clinical history of CAD and EF > 0.6, and 81 controls with no history of CAD. The Cambridge Cognitive Examination of the Elderly (CAMCOG) was the primary outcome measure. Secondary measures included the California Verbal Learning Test (CVLT), digit coding and copying, Hospital Anxiety and Depression Scale (HADS), and the short form health survey (SF36). Endpoints were collected at baseline and after 12 and 24 months.

Results: The adjusted CAMCOG scores of CHF participants declined 0.9 points over two years (p = 0.022) compared with controls without CAD. There were no differences between the groups on other cognitive measures. Participants with CHF and with CAD experienced similar changes in cognitive function over two years. Left ventricular EF and six-minute walk test results could not explain the observed associations.

Conclusions: The changes in cognitive function and mood associated with CHF over two years are subtle and not specific to CHF.

Background: Acute exposure to sedative drugs may induce memory impairment, but there is mixed evidence that long-term sedative use may result in incident cognitive decline. The objective of this study was to investigate the use of sedative drugs and incident cognitive decline in a population-based sample of persons aged 75 years and older.

Methods: The study sample comprised 781 participants in the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study in Kuopio, Finland. Data on health status, drug use, and sociodemographic factors were elicited during annual nurse interviews from 2004 to 2007. A linear mixed model was used to compare change in Mini-Mental State Examination (MMSE) scores (2005–2007) among users of sedative drugs in 2004 and 2005 (n = 139) to non-users of sedative drugs from 2004 to 2007 (n = 310). The model was adjusted for covariates including age, gender, education, depressive symptoms and antipsychotic use.

Results: Unadjusted mean MMSE scores were 27.50 in 2005, 26.58 in 2006, and 25.95 in 2007 among users of sedative drugs. Unadjusted mean MMSE scores were 28.05 in 2005, 27.61 in 2006, and 27.09 in 2007 among non-users of sedative drugs. Adjusted mean MMSE scores were 0.31 points lower in 2005, 0.62 points lower in 2006, and 0.93 lower in 2007 among users compared to non-users of sedative drugs (P = 0.051).

Conclusions: Sedatives were not associated with statistically significant cognitive decline. However, clinicians should maintain a judicious approach to prescribing sedative drugs given the risk of adverse drug events.

Background: This study sought to assess whether lower school performance in childhood is a risk factor for dementia in old age.

Methods: Participants aged 60 years or more (n = 111) with documented proof from schools were included. Grades in three subjects – Portuguese, mathematics, and geography – were recorded and the mean final grade in all disciplines were assessed. Dementia was diagnosed using DSM-IV criteria. Sociodemographic data, school performance, and years of education were ascertained by checking documents issued by schools. Health status (hypertension and diabetes) were self reported. Regression models were used to assess the role of school performance and years of education on the risk of dementia.

Results: Dementia was diagnosed in 22 subjects. Higher school performance and years of education decreased the chance of dementia by 79% (OR = 0.21; CI 0.08–0.58) and 21% (OR = 0.79; CI 0.69–0.91), respectively. After adjustments for sociodemographic and clinical variables, only school performance remained statistically significant (OR = 0.06; CI 0.01–0.71).

Conclusions: Education in early life should be viewed as a health issue over the life course. School attainment in certain basic disciplines may be important for cognitive reserve and prevention of dementia in the elderly.

Background: Neuropsychiatric symptoms (NPS) are highly prevalent among nursing home patients with dementia. Several studies have investigated subsyndromes of NPS but the stability of these subsyndromes over time has rarely been examined. We have examined the stability over time of the factor structure of the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) in a large sample of nursing-home patients with dementia.

Methods: Nursing-home patients with dementia were assessed with the NPI-NH at baseline (n = 895), and at 12-month (n = 592) and 31-month (n = 278) follow-up assessments, giving three partly overlapping samples. Exploratory factor analysis was done to investigate neuropsychiatric subsyndromes of the NPI-NH at each assessment in these samples.

Results: Three- or four-factor solutions were found, termed agitation, psychosis, apathy, and affective symptoms. Depression and anxiety (affective), delusion and hallucination (psychosis), and agitation and irritability (agitation) were the symptoms that most often co-occurred in the same factor. Apathy did not load together with affective symptoms at any of the assessments.

Conclusions: Subsyndromes of the NPI-NH are relatively stable over 31-month follow-up assessments in nursing-home patients with dementia, indicating that these subsyndromes may be useful for following the natural course of symptoms as well as observing the effect of interventions. Our findings lend support to the distinction between apathy and affective symptoms, which may have important clinical implications.

Background: Anemia and dementia are common diseases among the elderly, but conflicting data are available regarding an association between these two conditions. We analyzed data from the São Paulo Ageing & Health Study to address the relationship between anemia and dementia.

Methods: This cross-sectional observational study included participants aged 65 years and older from a deprived area of the borough of Butantan, São Paulo, Brazil. Data about demographics, education, income, and cognitive and daily life function were collected, as well as blood samples. Anemia and dementia were defined according to WHO and DSM-IV criteria, respectively.

Results: Of the 2267 subjects meeting the inclusion criteria, 2072 agreed to participate in the study; of whom 1948 had a valid total blood count and were included in the analysis. Anemia was diagnosed in 203 (10.2%) participants and dementia in 99 (5.1%). The frequency of anemia was higher in patients with dementia according to univariate analysis (odds ratio (OR) = 2.00, 95% confidence interval (CI) = 1.17–3.41, p = 0.01), but this association was not present after adjusting for age (OR = 1.33, 95% CI = 0.76–2.33, p = 0.32). Further multivariate adjustment did not change the results.

Conclusion: Although anemia and dementia are frequent disorders in older people, we found their relationship to be mediated exclusively by aging in this low-income population from São Paulo.

Background: The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months.

Methods: The sample consisted of 102 patients with mild AD and their primary caregivers from the Danish Alzheimer's Disease Intervention Study. QoL was assessed with the proxy-rated (primary caregivers) Quality of Life in Alzheimer Disease scale (QOL-AD) and the EuroQuol Visual Analogue Scale (EQ-VAS) scale. The Cornell Scale for Depression in Dementia (CSDD), Alzheimer's Disease Cooperative Study, Activities of Daily living Inventory (ADCS-ADL), Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI-Q) were also applied. Evaluations were conducted at baseline and at 12 and 36 months follow-up.

Results: There was a significant decline in mean QoL assessed by both the QOL-AD and the EQ-VAS (p < 0.001). There were vast individual differences in the QoL scores on both scales at 12 and 36 months’ follow-up. Mean change from baseline in QOL-AD was significantly associated with change in CSDD, ADCS-ADL and MMSE scores at 12 months and with ADCS-ADL score at 36 months.

Conclusion: QoL is a subjective concept and may not be influenced by the degree of cognitive dysfunction. Future studies should investigate the factors for individual variations in order to understand the nature of change of QoL in AD and the wide variation in QoL scores over time.

Background: Clinicians and researchers working with dementia caregivers typically assess caregiver stress in a clinic or research center, but caregivers’ stress is rooted at home where they provide care. This study aimed to compare ratings of stress-related measures obtained in research settings and in the home using ecological momentary assessment (EMA).

Methods: EMA of 18 caregivers (mean age 66.4 years ±7.8; 89% females) and 23 non-caregivers (mean age 66.4 years ±7.9; 87% females) was implemented using a personal digital assistant. Subjects rated their perceived stress, fatigue, coping with current situation, mindfulness, and situational demand once in the research center and again at 3–4 semi-random points during a day at home. The data from several assessments conducted at home were averaged for statistical analyses and compared with the data collected in the research center.

Results: The testing environment had a differential effect on caregivers and non-caregivers for the ratings of perceived stress (p < 0.01) and situational demand (p = 0.01). When tested in the research center, ratings for all measures were similar between groups, but when tested at home, caregivers rated their perceived stress as higher than non-caregivers (p = 0.02). Overall, caregivers reported higher perceived stress at home than in the research center (p = 0.02), and non-caregivers reported greater situational demand in the research center than at home (p < 0.01).

Conclusions: The assessment method and environment affect stress-related outcomes. Evaluating participants in their natural environment provides a more sensitive measure of stress-related outcomes. EMA provides a convenient way to gather data when evaluating dementia caregivers.

Background: Paranoid delusions are a common and difficult-to-manage feature of Alzheimer's disease (AD). We investigated the neuroanatomical correlates of paranoid delusions in a cohort of AD patients, using magnetic resonance imaging (MRI) to measure regional volume and regional cortical thickness.

Methods: 113 participants with probable AD were assessed for severity of disease, cognitive and functional impairment. Presence and type of delusions were assessed using the Neuropsychiatric Inventory (NPI). Structural MRI images were acquired on a 1.5T scanner, and were analyzed using an automated analysis pipeline.

Results: Paranoid delusions were experienced by 23 (20.4%) of the participants. Female participants with paranoid delusions showed reduced cortical thickness in left medial orbitofrontal and left superior temporal regions, independently of cognitive decline. Male participants with delusions did not show any significant differences compared to males without delusions. An exploratory whole brain analysis of non-hypothesized regions showed reduced cortical thickness in the left insula for female participants only.

Conclusion: Frontotemporal atrophy is associated with paranoid delusions in females with AD. Evidence of sex differences in the neuroanatomical correlates of delusions as well as differences in regional involvement in different types of delusions may be informative in guiding management and treatment of delusions in AD.

Background: The negative image of Alzheimer's disease (AD) in our society has a substantial impact on treating, caring for and integrating those suffering from the disease and their relatives. Little research has been conducted on social perception of AD in the community.

Methods: The aim of this study was to investigate the perception, knowledge, opinions and beliefs about AD in the French population. A cross-sectional telephone survey of 2013 randomly selected community-dwelling people aged 18 years and over was conducted. Multivariate logistic regressions were used for identifying predictors of the personal fear of developing AD, both for the global sample and for different age groups.

Results: Sixty percent of the sample reported personal fear of developing AD. This attitude was strongly related to age, becoming predominant among the elderly. In the middle-aged group, personal fear of developing AD was highest in women with poor self-perceived health and, in particular, those who cared for someone with AD. Being a caregiver or knowing someone with the disease was also strongly associated with fear among younger adults aged 18–34.

Conclusions: These results serve as an incentive for developing special education and prevention programs focused on different age groups and caregivers of AD.

Background: Very few studies from India have studied the phenomenology of delirium. The aim of the present study was to study the phenomenology as measured using the Delirium Rating Scale-Revised-98 (DRS-R98), the associated etiologies and the outcome of delirium among the elderly participants seen by the consultation-liaison psychiatric service in India. In addition, an attempt was made to study the factor structure of symptoms using principal components analysis.

Methods: The case notes of 109 elderly patients referred to psychiatry liaison services were reviewed.

Results: The mean age of the sample was 73.35 years (SD: 7.44; range 65–95 years) and two-thirds of the sample had hospital emergent delirium. The mean DRS-R98 severity score was 18.77 and the DRS-R98 total score was 24.81. In 15 patients the DRS-R98 scores were in the subsyndromal range. Among the various symptoms present, most patients had sleep-wake cycle disturbance, disturbance in orientation, attention and short-term memory impairments, fluctuation of symptoms, temporal onset of symptoms and a physical disorder. Principal components analysis identified three factors which explained 43.5% of variance of symptomatology and it yielded a three-factor structure. Endocrine/metabolic disturbances were the commonest associated etiological category with delirium. The mean hospital stay after being referred to psychiatry referral services was 8.89 days, after which delirium improved in 58.7% of cases. The mortality rate during the inpatient stay was 16.5%.

Conclusions: Results suggest that the symptoms of delirium as assessed by DRS-R98 separate out into a three-factor structure. Delirium is commonly associated with metabolic endocrine disturbances and about one-sixth of the patients die during the short inpatient stay.

Background: Anxiety and depression are prevalent in patients with chronic obstructive pulmonary disease (COPD). This study evaluates the sensitivity and specificity of two self-administered anxiety rating scales in older people with COPD. The Geriatric Anxiety Inventory (GAI) and the Hospital Anxiety and Depression Scale (HADS) are established useful screening tools but they have not been previously validated in this population.

Methods: Older people with COPD completed the GAI and the HADS along with a structured diagnostic psychiatric interview, the Mini International Neuropsychiatric Interview (MINI). The outcomes of both rating scales were compared against the diagnosis of anxiety disorders based on the MINI. Receiver operating characteristic (ROC) curves were used to identify the optimal diagnostic cut points for each scale.

Results: Fourteen (25.5%) of the 55 participants, were diagnosed with an anxiety disorder. Mean GAI and HADS-anxiety subscale scores were significantly higher in subjects with an anxiety disorder than those without the diagnosis (p = 0.002 and 0.005 respectively). Both scales demonstrated moderate diagnostic value (area under the ROC curve was 0.83 for GAI and 0.79 for HADS). Optimal cut points were ≥3 (GAI) and ≥4 (HADS-anxiety subscale). At these cut-points, the GAI had a sensitivity of 85.7%, specificity of 78.0% and the HADS had a sensitivity of 78.6%, specificity 70.7%.

Conclusion: Our results support the use of the GAI and HADS as screening instruments for anxiety disorders in older people with COPD. The optimal cut points in this population were lower than previously recommended for both rating scales. The results of this study should be replicated before these cut points can be recommended for general use in older people with COPD.

Background: The Geriatric Anxiety Inventory (GAI) was developed for assessing anxiety in older adults. The objectives of this work were: (a) to analyze the psychometric properties of the Spanish version of the GAI, and (b) to explore the associations between anxiety and other variables related to emotional distress (depression) and emotion regulation (rumination, experiential avoidance, and emotion suppression).

Methods: Three-hundred-and-two people (75.5% female) aged 60 years and over living in the community participated in this study. Anxiety, depression, rumination, suppression and experiential avoidance were measured.

Results: Three factors explaining 50.11% of the variance were obtained. The obtained internal consistency for the total scale was 0.91, with alphas ranging between 0.71 and 0.89 for the factors. Significant associations between all the GAI factors, the GAI total score, and depression, rumination, and experiential avoidance were found (all p < 0.01). Women reported higher scores than men for both the GAI total score and for all of the subscales. However, no significant gender differences were found between people with scores higher than the cut-off score for the GAI.

Conclusions: The results of this study suggest that the Spanish version of the GAI displays good psychometric properties. Further, our data suggest that the scale can be recommended for measuring anxiety in non-clinical older Spanish persons, and may be a useful instrument to be used in research studies aimed at analyzing anxiety and its correlates among older adults.

Background: Women report higher rates of depression and anxiety than men; however, it is uncertain whether this gender difference continues into advanced old age.

Methods: 78 men and 111 women aged 82–87 years from the Men, Women and Ageing Project completed measures of anxiety (Geriatric Anxiety Inventory), depression (Patient Health Questionnaire; PHQ9), general psychological well-being (Mental Health subscale of SF-36), general health (general health item of SF-36) and cognitive status (Telephone Interview for Cognitive Status; TICS).

Results: Results revealed no significant gender differences on any of the psychological measures, after controlling for cognitive status, general health and education.

Conclusion: These results support the proposition that the female predominance in psychological distress diminishes with increasing age. The congruence between men and women may reflect changes in identity associated with age or the effect of decreased emotional valence of some social roles.

Background: Depression is a common disorder in late life. As the elderly population continues to grow worldwide, depression is also likely to become an increasing health problem. The aim of this study was to examine changes in prevalence of depression in various age cohorts over an 11-year period.

Methods: This study involved two cross-sectional studies (HUNT 2 and HUNT 3) of all adult inhabitants of the Norwegian county of Nord-Trøndelag with an 11 year-interval between the two studies. The participants aged 45 years or above at HUNT 2 and with a valid depression rating at both HUNT 2 (baseline) and HUNT 3 (follow-up) (N = 16517), were included and divided into five-year age cohorts. Depression was measured by the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).

Results: A significant increase in depression was found in all age cohorts from 76 years at follow-up, with the greatest increase (9.6%) in the oldest age cohort (86–90 years at follow-up). The incidence of depression is increasing with age, with over 10% new cases in all age cohorts aged 81 years and above at follow-up. About 5% of the participants in all age cohorts reported depression at both measure points, and there is a decrease in recovery from depression from baseline to follow-up with increasing age.

Conclusions: We found increased prevalence of depression and a large number of new cases of depression in the oldest age cohorts.

Background: Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients’ adherence to antidepressants and their beliefs about and knowledge of the medication.

Methods: Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs.

Results: 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as “my health depends on antidepressants” (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects.

Conclusions: Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients’ beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.

The authors wish to make readers aware that two of the symptoms on the HAM-D – loss of weight and loss of insight – were reverse coded in the early assessments. The analyses have been corrected and there are minor changes to the paper. The mean (SD) for loss of weight was 0.59 (0.84), while the mean (SD) for loss of insight was 0.24 (0.51). A three-cluster model still best fit the data and the profiles were similar to those presented earlier, but the distribution of patients changed. A total of 39% had the lowest mean scores, and 15% had the highest mean scores across symptoms. Clusters were differentiated by sex, education, stress, and ADL and IADL limitations. The variable reduction techniques resulted in some slight changes to the symptom groupings but the representative symptoms and resulting latent class analysis were unchanged. Specific details of the changes are available from the corresponding author upon request.