The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD.

We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013.

We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of “clinically significant A/A.” There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials.

This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.

Mild cognitive impairment (MCI) is a diagnostic classification used to describe patients experiencing cognitive decline but without a corresponding impairment in daily functioning. Over the years, MCI diagnostic criteria have undergone major changes that correspond to advancements in research. Despite these advancements, current diagnostic criteria for MCI contain issues that are reflected in the research literature.

A review of the available MCI literature was conducted with emphasis given to tracing MCI from its conceptual underpinnings to the most current diagnostic criteria. A clinical vignette is utilized to highlight some of the limitations of current MCI diagnostic criteria.

Issues are encountered when applying MCI diagnostic criteria due to poor standardization. Estimates of prevalence, incidence, and rates of conversion from MCI to dementia reflect these issues.

MCI diagnostic criteria are in need of greater standardization. Recommendations for future research are provided that could potentially bring more uniformity to the diagnostic criteria for MCI and, therefore, more consistency to the research literature.

The Montreal Cognitive Assessment (MoCA) is used for screening mild cognitive impairment (MCI), and the Beijing version (MoCA-BJ) is widely used in China. We aimed to develop a computerized tool for MoCA-BJ (MoCA-CC).

MoCA-CC used person-machine interaction instead of patient-to-physician interaction; other aspects such as the scoring system did not differ from the original test. MoCA-CC, MoCA-BJ and routine neuropsychological tests were administered to 181 elderly participants (MCI = 96, normal controls [NC] = 85).

A total of 176 (97.24%) participants were evaluated successfully by MoCA-CC. Cronbach's α for MoCA-CC was 0.72. The test–retest reliability (retesting after six weeks) was good (intraclass correlation coefficient = 0.82; P < 0.001). Significant differences were observed in total scores (t = 9.38, P < 0.001) and individual item scores (t = 2.18–8.62, P < 0.05) between the NC and MCI groups, except for the score for “Naming” (t = 0.24, P = 0.81). The MoCA-CC total scores were highly correlated with the MoCA-BJ total scores (r = 0.93, P < 0.001) in the MCI participants. The area under receiver–operator curve for the prediction of MCI was 0.97 (95% confidence interval = 0.95–1.00). At the optimal cut-off score of 25/26, MoCA-CC demonstrated 95.8% sensitivity and 87.1% specificity.

The MoCA-CC tool developed here has several advantages over the paper-pencil method and is reliable for screening MCI in elderly Chinese individuals, especially in the primary clinical setting. It needs to be validated in other diverse and larger populations.

The Brief Cognitive Status Exam (BCSE) is a new, optional subtest of the Wechsler Memory Scale-IV (WMS-IV) developed for rapid detection of cognitive deficits. We examined the clinical validation of the Dutch version of the BCSE in older adults with mild cognitive impairment (MCI) or dementia, comparing it to the Mini-Mental State Examination (MMSE).

BCSE and MMSE were administered in 39 older adults with MCI, 51 with dementia and 96 matched healthy controls.

Our results show that the BCSE is a valid screening instrument, with psychometric properties similar to the widely used MMSE. High correlations were found between the BCSE and MMSE (r = 0.79, n = 183, p < 0.001). Furthermore, a BCSE cut-off score ≤ 42 revealed a sensitivity of 96% a specificity of 92%, a positive predictive value of 86% and a negative predictive value of 97%, whereas the MMSE cut-off score of ≤ 24 showed values of 84%, 96%, 91%, and 92%, respectively. Sensitivity, specificity, positive and negative predictive values to detect MCI compared to controls was 81%, 80%, 61%, and 92%, respectively, on the BCSE, with a cut-off score of ≤ 46, and 84%, 76%, 57%, and 92%, respectively, on the MMSE, with a cut-off score of ≤ 27.

The Dutch version of the BCSE is a clinically valid screening instrument for the detection of cognitive impairment in patients with dementia. Nevertheless, for distinguishing older adults with MCI from healthy controls both the BCSE and MMSE have limitations.

With the proportion of older adults in Hong Kong projected to double in size in the next 30 years, it is important to develop measures for detecting individuals in the earliest stage of Alzheimer's disease (AD, 0.5 in Clinical Dementia Rating, CDR). We tested the utility of a non-verbal prospective memory task (PM, ability to remember what one has to do when a specific event occurs in the future) as an early marker for AD in Hong Kong Chinese.

A large community dwelling sample of older adults who are healthy controls (CDR 0, N = 125), in the earliest stage of AD (CDR 0.5, N = 125), or with mild AD (CDR 1, N = 30) participated in this study. Their reaction time/accuracy data were analyzed by mixed-factor analyses of variance to compare the performance of the three CDR groups. Logistic regression analyses were performed to test the discriminative power of these measures for CDR 0 versus 0.5 participants.

Prospective memory performance declined as a function of AD severity: CDR 0 > CDR 0.5 > CDR 1, suggesting the effects of early-stage AD and AD progression on PM. After partialling out the variance explained by psychometric measures (e.g., ADAS-Cog), reaction time/accuracy measures that reflected the PM still significantly discriminated between CDR 0 versus 0.5 participants in most of the cases.

The effectiveness of PM measures in discriminating individuals in the earliest stage of AD from healthy older adults suggests that these measures should be further developed as tools for early-stage AD discrimination.

Cognitive impairment is underrecognized and misdiagnosed among community-dwelling older adults. At present, there is no consensus about which cognitive screening tool represents the “gold standard.” However, one tool that shows promise is the Brief Cognitive Assessment Tool (BCAT), which was originally validated in an assisted living sample and contains a multi-level memory component (e.g. word lists and story recall items) and complex executive functions features (e.g. judgment, set-shifting, and problem-solving).

The present study cross-validated the BCAT in a sample of 75 community-dwelling older adults. Participants completed a short battery of several individually administered cognitive tests, including the BCAT and the Montreal Cognitive Assessment (MoCA). Using a very conservative MoCA cut score of <26, the base rate of cognitive impairment in this sample was 35%.

Adequate internal consistency and strong evidence of construct validity were found. A receiver operating characteristic (ROC) curve was calculated from sensitivity and 1-specificity values for the classification of cognitively impaired versus cognitively unimpaired. The area under the ROC curve (AUC) for the BCAT was .90, p < 0.001, 95% CI [0.83, 0.97]. A BCAT cut-score of 45 (scores below 45 suggesting cognitive impairment) resulted in the best balance between sensitivity (0.81) and specificity (0.80).

A BCAT cut-score can be used for identifying persons to be referred to appropriate healthcare professionals for more comprehensive cognitive assessment. In addition, guidelines are provided for clinicians to interpret separate BCAT memory and executive dysfunction component scores.

The Cambridge Cognitive Examination-Revised (CAMCOG-R) is a sensitive screening tool for the early diagnosis of dementia in older adults. Overall performance on the CAMCOG-R is influenced by educational attainment. Few studies have, however, examined the association between educational attainment and performance on the individual CAMCOG subscales. We aimed to address this question in a sample from a low-and middle-income country (LAMIC), where resource constraints may have compromised access to, and quality of, education for many older adults.

Participants, all over 60 years of age, were 51 cognitively healthy community-dwelling volunteers and 47 individuals diagnosed with mild-moderate stage Alzheimer's disease (AD). Most participants had some high school education. They were administered the CAMCOG-R under standardized conditions.

Within both the control and AD patient groups, there were significant associations between years of completed education and CAMCOG-R total score, MMSE score, and CAMCOG-R Language subscale score. In both groups, level of education was not associated with scores on these subscales: in controls, recent memory, R2 = .21, p = .055, learning memory, R2 = .16, p = .398, attention/calculation, R2 = .19, p = .467, and perception, R2 = .18, p = .984; in AD patients, recent memory, R2 = .14, p = .340, learning memory, R2 = .03, p = .680, perception, R2 = .09, p = .723, and attention/calculation, R2 = .19, p = .097.

Some CAMCOG-R subscale scores were more strongly associated with educational attainment than others. Importantly, however, performance on the recent memory and learning memory subscales was not affected by education. These subscales are sensitive indicators of amnestic mild cognitive impairment (MCI) and early AD. These subscales may therefore remain valid for use as an AD screening tool in resource-poor healthcare settings.

This investigation aimed to develop a screening tool based on the Cognitive Inventory of Subjective Distress (CISD). Two studies were designed in order to test the second-order factorial structure of the CISD, to shorten its length and to assess its replicability on a second large independent sample.

We recruited a first sample (n = 290) living at home or in retirement centers and a second community-based sample (n = 1,429). The first sample completed the original CISD as well as cognitive, autonomy, anxiety, and depression assessments. The second sample completed the Short-CISD (S-CISD).

Factor analyses supported a second-order factorial structure allowing to engage in a refinement of the scale. We retained seven items corresponding to a dimension of cognitive schemas. Confirmatory Factor Analysis (CFA) demonstrated that the S-CISD exhibited satisfying psychometric properties as well as factorial replicability and structural invariance in two different samples. Further, the internal consistency of the S-CISD is acceptable.

The S-CISD is a relevant screening tool for rapidly assessing psychological distress. It is directed towards old and very old individuals either living at home or in a retirement center, while also taking into account the fatigability and potential cognitive impairment of this population. This screening tool can be confidently used for psychopathological assessment and can serve as a baseline for following patients over time or in the course of therapy.

Previous research on wisdom has suggested that wisdom is comprised of cognitive, reflective, and affective components and has developed and validated wisdom measures based on samples from Western countries. To apply the measurement to Eastern cultures, the present study revised an existing wisdom scale, the three-dimensional wisdom scale (3D-WS, Ardelt, 2003) for the Korean cultural context.

Participants included 189 Korean heritage adults (age range 19–96) living in Los Angeles. We added a culturally specific factor of wisdom to the 3D-WS: Modesty and Unobtrusiveness (Yang, 2001), which captures an Eastern aspect of wisdom. The structure and psychometrics of the scale were tested. By latent cluster analysis, we determined acculturation subgroups and examined group differences in the means of factors in the revised wisdom scale (3D-WS-K).

Three factors, Cognitive Flexibility, Viewpoint Relativism, and Empathic Modesty were found using confirmatory factor analysis. Respondents with high biculturalism were higher on Viewpoint Relativism and lower on Empathic Modesty.

This study discovered that a revised wisdom scale had a distinct factor structure and item content in a Korean heritage sample. We also found acculturation influences on the meaning of wisdom.

To date, no studies have examined the relationship between cognitive disorders and personality disorders. Our aim was to investigate the association between dependent personality disorder (DPD) and cognitive disorders in Central Africa.

Between 2011 and 2012, a cross-sectional multicenter population-based study was carried out in rural and urban areas of the Central African Republic (CAR) and the Republic of Congo (ROC). Participants aged ≥65 years were interviewed using the Community Screening Interview for Dementia (CSI-D). Elderly people who performed poorly (CSI-D cognitive tests score or COGSCORE ≤ 24.5/30) were clinically assessed by neurologists and underwent further psychometric testing. The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition and Petersen criteria were required for the diagnosis of dementia and mild cognitive impairment (MCI) respectively. DPD was assessed using the Personality Diagnostic Questionnaire-4+. Socio-demographic, vascular, and psychological factors were also documented. Multivariate multinomial logistic regression models were used to estimate the associations.

Of the 2,002 participants screened, 860 and 912 had data for cognitive status and DPD in CAR and ROC respectively. In fully adjusted models, DPD was significantly associated with MCI in ROC (Odds Ratio (OR) = 2.2, 95% CI: 1.0–4.7) and CAR (OR = 2.1, 95% CI: 1.1–4.0) and with dementia only in ROC (OR = 4.8, 95% CI: 2.0–11.7).

DPD was associated with cognitive disorders among elderly people in Central Africa. This association should be confirmed in other contexts. This study paves the way for research on the association between personality and cognitive impairment in Africa.

We determined the association between neighborhood socio-environmental factors and insomnia symptoms in a nationally representative sample of US adults aged >50 years.

Data were analyzed from two waves (2006 and 2010) of the Health and Retirement Study using 7,231 community-dwelling participants (3,054 men and 4,177 women) in the United States. Primary predictors were neighborhood physical disorder (e.g. vandalism/graffiti, feeling safe alone after dark, and cleanliness) and social cohesion (e.g. friendliness of people, availability of help when needed, etc.); outcomes were insomnia symptoms (trouble falling asleep, night awakenings, waking too early, and feeling unrested).

After adjustment for age, income, race, education, sex, chronic diseases, body mass index, depressive symptoms, smoking, and alcohol consumption, each one-unit increase in neighborhood physical disorder was associated with a greater odds of trouble falling asleep (odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.04–1.14), waking too early (OR = 1.05, 95% CI: 1.00–1.10), and, in adults aged ≥69 years (adjusting for all variables above except age), feeling unrested in the morning (OR = 1.11, 95% CI: 1.02–1.22 in 2006). Each one-unit increase in lower social cohesion was associated with a greater odds of trouble falling asleep (OR = 1.06, 95% CI: 1.01–1.11) and feeling unrested (OR = 1.09, 95% CI: 1.04–1.15).

Neighborhood-level factors of physical disorder and social cohesion are associated with insomnia symptoms in middle-aged and older adults. Neighborhood-level factors may affect sleep, and consequently health, in our aging population.

To date, few studies have investigated age differences in posttraumatic stress disorder (PTSD) symptoms and none has examined age differences across symptom clusters: avoidance, re-experiencing, and hyperarousal. The first objective of this study was to investigate age differences in PTSD and its three symptom clusters. The second objective was to examine age and indices of health as predictors of PTSD symptom severity.

Participants were 104 male veterans, aged 22 to 87 years, receiving specialized mental health outpatient services. Assessments included measures of health-related quality of life, pain severity, number of chronic health conditions, and symptoms of PTSD, both in total and on the symptom clusters.

There were significant age differences across age groups, with older veterans consistently reporting lower PTSD symptom severity, both in total and on each of the symptom clusters. Hierarchical regression analyses indicated that the inclusion of health indices accounted for significantly more variance in PTSD symptoms over and above that accounted for by age alone. Pain severity was a significant predictor of PTSD total and the three symptom clusters.

Conclusions: This is the first study to report lower levels of PTSD severity among older veterans across symptom clusters. These findings are discussed in relation to age differences in the experiencing and processing of emotion, autobiographical memory, and combat experiences. This study also emphasizes the importance of assessing pain in those with symptoms of PTSD, particularly older veterans who are less likely to receive specialized mental healthcare.

Painful physical symptoms (PPS) are prevalent among elderly patients with depression. We describe the impact of PPS on depression outcomes and quality of life (QOL) of elderly Asian patients with major depressive disorder (MDD).

This post hoc analysis of data from a three-month prospective observational study of East Asian MDD in- or out-patients focused on elderly patients aged ≥60 years. Depression severity was evaluated using the Hamilton depression (HAMD-17) and clinical global impression of severity (CGI-S) scales, while QOL was measured using EuroQOL (EQ-5D and EQ-VAS) instruments. PPS were rated using the modified somatic symptom inventory (SSI).

At baseline, depression was moderate to severe and 49% of the 146 elderly patients were painful physical symptom positive (PPS+). Bivariate analysis showed significant correlations between PPS and depression severity and QOL at baseline. Linear regression models showed the baseline factor most significantly associated with depression severity at three months was baseline PPS status. PPS+ patients had a mean increase of 2.87 points in their HAMD-17 rating and 0.77 points in their CGI-S score. Response and remission were significantly lower in PPS+ patients; response was 60% and remission was 40% in PPS+ patients while 82% and 66% in painful physical symptom negative (PPS−) patients. QOL at endpoint was lower in PPS+ patients.

PPS are common in elderly Asian patients with MDD and negatively influence depression outcomes and QOL. Patients with PPS had lower QOL at baseline, lower response and remission rates, higher severity of depression, and lower QOL after three months of treatment.

Geriatric psychiatry hospital beds are a limited resource. Our aim was to determine predictors of hospital length of stay (LOS) for geriatric patients with dementia admitted to inpatient psychiatric beds.

Admission and discharge data from a large urban mental health center, from 2005 to 2010 inclusive, were retrospectively analyzed. Using the resident assessment instrument - mental health (RAI-MH), an assessment that is used to collect demographic and clinical information within 72 hours of hospital admission, 169 geriatric patients with dementia were compared with 308 geriatric patients without dementia. Predictors of hospital LOS were determined using a series of general linear models.

A diagnosis of dementia did not predict a longer LOS in this geriatric psychiatry inpatient population. The presence of multiple medical co-morbidities had an inverse relationship to length of hospital LOS – a greater number of co-morbidities predicted a shorter hospital LOS in the group of geriatric patients who had dementia compared to the without dementia study group. The presence of incapacity and positive psychotic symptoms predicted longer hospital LOS, irrespective of admission group (patients with dementia compared with those without). Conversely, pain on admission predicted shorter hospital LOS.

Specific clinical characteristics generally determined at the time of admission are predictive of hospital LOS in geriatric psychiatry inpatients. Addressing these factors early on during admission and in the community may result in shorter hospital LOS and more optimal use of resources.

Older people who present to the emergency department (ED) often experience a significant delay to analgesia. This study compares the time to analgesia for cognitively impaired and cognitively intact older people diagnosed with a long bone fracture.

The aim of the study was to determine if cognitive impairment is associated with a delayed analgesic response. A 12-month exploratory study, using patient data, was conducted across four EDs. Medical records of 264 patients with long bone fractures were randomly selected.

The majority of patients waited longer than 60 minutes for analgesia. The median time to analgesia was longer for the cognitively impaired (149 minutes) compared with cognitively intact (72 minutes; Mann–Whitney U test: p < 0.001).

This study suggests that cognitive impairment is a significant risk factor for delayed analgesia response in the ED.

To investigate the effect of pre-emptive parecoxib sodium, given in addition to routine analgesic treatment, on post-operative cognitive function in elderly patients.

Seventy elderly patients were included, who were 65–82 years of age, 48–75 kg of weight, and ASA grade I-II. Preoperative mini mental state examination (MMSE) score was ≥21 points. Patients were randomly divided into two groups: control group (group C) and parecoxib sodium group (group P). Before induction of general anesthesia, 40 mg of parecoxib sodium was injected intravenously in group P and the same volume of saline was injected in group C. Patient-controlled intravenous analgesia (PCIA) containing fentanyl and tramadol was used for post-operative pain control. A 3 ml blood sample was obtained from the peripheral vein one day before surgery, 1, 4, 24, and 72 h after surgery, and plasma cortisol, IL-6 and S100β concentrations were measured. Cognitive function was evaluated by measuring the MMSE score and a neurological test battery within 72 h after surgery. The occurrence of post-operative cognitive dysfunction (POCD), the dosage of fentanyl and tramadol used in PCIA, and the rate of additional fentanyl administration were recorded.

Compared to group C, post-operative plasma cortisol concentration decreased, the amount of fentanyl and tramadol used in PCIA was reduced, the rate of additional fentanyl administration decreased, and the rate of POCD was reduced in group P (P < 0.05).

Pre-emptive analgesia with 40 mg of parecoxib sodium can reduce the incidence of POCD in elderly patients.

Delirium is a major cause of morbidity and mortality amongst hospital patients. Previous studies have shown that it is often poorly recognized and managed. We wanted to assess the impact of a multifaceted intervention on delirium management.

A pre/post-intervention design was used. The local hospital delirium guideline was adapted into A7 sized cards and A3/A2 posters. Cards were distributed to junior doctors and teaching sessions were held. Computer screen savers were displayed and delirium promotion days held. The pre/post-intervention data were used to audit the following: delirium knowledge through questionnaires, documented use of the confusion assessment method (CAM) and identification and management of eight common precipitating factors. Re-audit was four months post baseline with interventions within this period. χ2 tests were used for statistical analysis.

A convenience sample of randomly selected doctors in postgraduate training posts completed 100 questionnaires and 25 clinical notes were selected via retrospective identification of delirium. Results from questionnaires demonstrated significant improvements in: recognizing CAM as the diagnostic tool for delirium (24% vs. 71%, p < 0.01); identifying haloperidol as first line in pharmacological management (55% vs. 98%, p <0.01) and its correct dose (40% vs. 67%, p <0.01). In clinical practice, there was significant improvement in documentation of CAM for inpatient delirium assessments (0% vs. 77%, p <0.01). Trainees found the delirium card “very helpful” (82%) and carried it with them at all times (70%).

This multifaceted intervention increased CAM use in delirium recognition and improved the knowledge of pharmacological management. The delirium card was highly popular.