Background: Although knowledge of established risk factors for Alzheimer's disease (AD) can logically contribute to the search for predictors of the progression of cognitive impairment, it has not yet been firmly established where in the cognitive impairment process these risk factors exert their effects and how to predict quantitatively for the progression of mild cognitive impairments (MCI) to AD. This study aimed to determine whether known risk factors increased the risk of progression from MCI to AD and to make prediction based on transition probabilities.

Methods: Based on ten examinations of 600 community-dwelling MCI residents and cognitive assessments to classify individuals into MCI, global impairment, and AD, a multi-state Markov Cox's regression model was used and the hazard ratios with their confidence intervals and transition probabilities were estimated.

Results: Multivariate analysis showed that gender, age, and hypertension were statistically significant predictors of transition from MCI to global impairment; age, education, and reading statistically influenced transition from global impairment to MCI; gender, age, hypertension, diabetes, and apolipoprotein E geneε4 status were statistically associated with transition from global impairment to AD. Subjects at MCI were more likely (67%) to remain in that cognitive state at the next cognitive assessment than to transition to cognitive deterioration. For global impairment, probability of remaining in the same state was only 18% and that of forward transition was three times more likely than that of backward transition.

Conclusions: Known risk factors influenced differently for different transitions. Transition from global impairment was more likely to worsen to severe cognitive deterioration than transition from MCI.

Background: The aim of this study was to identify the neural correlates of each component of the clock drawing test (CDT) in drug-naïve patients with Alzheimer's disease (AD) using single photon emission computed tomography.

Methods: The participants were 95 drug-naïve patients with AD. The Rouleau CDT was used to score the clock drawings. The score for the Rouleau CDT (R total) is separated into three components: the scores for the clock face (R1), the numbers (R2), and the hands (R3). A multiple regression analysis was performed to examine the relationship of each score (i.e. R total, R1, R2, and R3) with regional cerebral blood flow (rCBF). Age, gender, and education were included as covariates. The statistical threshold was set to a family-wise error (FWE)-corrected p value of 0.05 at the voxel level.

Results: The R total score was positively correlated with rCBF in the bilateral parietal and posterior temporal lobes and the right middle frontal gyrus. R1 was not significantly positively correlated with rCBF, R2 was significantly positively correlated with rCBF in the right posterior temporal lobe and the left posterior middle temporal lobe, and R3 was significantly positively correlated with rCBF in the bilateral parietal lobes, the right posterior temporal lobe, the right middle frontal gyrus, and the right occipital lobe.

Conclusions: Various brain regions were associated with each component of the CDT. These results suggest that an assessment of these components is useful for the detection of localization of brain damage.

Background: Differences in the level of cognitive compromise between individuals following brain injury are thought to arise from underlying differences in cognitive reserve. The level of cognitive reserve attained by an individual is influenced by both genetic and life experience factors such as educational attainment and occupational history. The Tasmanian Healthy Brain Project (THBP) is a world-first prospective study examining the capacity of university-level education to enhance cognitive reserve in older adults and subsequently reduce age-related cognitive decline and risk for neurodegenerative disease.

Methods: Up to 1,000 adults aged 50–79 years at the time of entry into the study will be recruited to participate in the THBP. All participants will be healthy and free of significant medical, psychological, or psychiatric illness. Of the participant sample, 90% will undertake a minimum of 12 months part-time university-level study as an intervention. The remaining 10% will act as a control reference group. Participants will complete an annual comprehensive assessment of neuropsychological function, medical health, socialization, and personal well-being. Premorbid estimates of past cognitive, education, occupational, and physical function will be used to account for the mediating influence of prior life experience on outcomes. Potential contributing genetic factors will also be explored.

Results: Participant results will be assessed annually. Participants displaying evidence of dementia on the comprehensive neuropsychological assessment will be referred to an independent psycho-geriatrician for screening and diagnosis.

Conclusions: The THBP commenced in 2011 and is expected to run for 10–20 years duration. To date, a total of 383 participants have been recruited into the THBP.

Background: Delirium in elderly patients is associated with various long-term sequelae that include cognitive impairment and affective disturbances, although the latter is understudied.

Methods: For a prospective cohort study of elderly patients undergoing hip fracture surgery, baseline characteristics and affective and cognitive functioning were assessed preoperatively. During hospital admission, presence of delirium was assessed daily. Three months after hospital discharge, affective and global cognitive functioning was evaluated again in patients free from delirium at the time of this follow-up. This study compared baseline characteristics and affective functioning between patients with and without in-hospital delirium. We investigated whether in-hospital delirium is associated with increased anxiety and depressive levels, and post-traumatic stress disorder (PTSD) symptoms three months after discharge.

Results: Among 53 eligible patients, 23 (43.4%) patients experienced in-hospital delirium after hip fracture repair. Patients who had experienced in-hospital delirium showed more depressive symptoms at follow-up after three months compared to the 30 patients without in-hospital delirium. This association persisted in a multivariate model controlling for age, baseline cognition, baseline depressive symptoms, and living situation. The level of anxiety and symptoms of PTSD at follow-up did not differ between both groups.

Conclusion: This study suggests that in-hospital delirium is associated with an increased burden of depressive symptoms three months after discharge in elderly patients who were admitted to the hospital for surgical repair of hip fracture. Symptoms of depression in patients with previous in-hospital delirium cannot be fully explained by persistent (sub)syndromal delirium or baseline cognitive impairment.

Trial name: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. URL: http://clinicaltrials.gov/ct2/show/NCT00497978?term=taurine+hip+fracture&rank=1. Registration number: NCT00497978.

Background: The objectives of this study were to examine the factors modifying the relationship between cortisol level and prevalent/incident cognitive impairment in older adults and to verify whether these relationships were non-linear.

Methods: Data were collected from 1,226 individuals aged 65 and older by two in-home interviews separated by 12 months. Cortisol level was measured using saliva samples taken at the beginning of the baseline interview before cognitive, mental, and physical health evaluations. Prevalent and incident cognitive impairment were defined using the Mini-Mental State Examination scores according to normative data for age, education level, and sex.

Results: High morning cortisol level increased the risk of incident cognitive impairment in participants with anxiety or depressive episode while low cortisol level increased the risk in participants without anxiety or depressive episode. In high educated participants, but not in low educated participants, high morning cortisol level was associated with prevalent cognitive impairment and high afternoon cortisol level increased the risk of incident cognitive impairment. The results also suggested that lower morning cortisol values could increase the risk of incident cognitive impairment in individuals with few chronic diseases. A curvilinear relationship was observed between morning cortisol and the probability of incident cognitive impairment, but further analyses suggested that it was likely explained by anxiety and depressive episode.

Conclusions: These results suggest that cognitive impairment in older adults is linked to higher or lower cortisol level depending on characteristics such as anxiety, depressive episode, education level, and physical health.

Background: Connecting willing patients with dementia to suitable clinical research studies has been historically challenging. The United Kingdom Dementia and Neurodegenerative Research Network (DeNDRoN) was established to link patients into high-quality studies. One component is DemReg, a register of dementia patients and their carers who have agreed to be approached regarding future research studies. The limited literature highlights the predominance of altruism mediating research register participation. The objective of this study was to understand the motivations of patients and carers to participate in DemReg.

Methods: There were 107 participants in the study, interviewed using a questionnaire to determine which factors were important in their decision to be on the register. The study compared the proportion of the altruistic motivations articulated with the proportion of the other answers offered.

Results: The two most important motivators for registering on DemReg were to help others (44%; p < 0.001) or themselves (29%; p < 0.001) and altruistic motives took precedence over those for personal benefit. Participants were not motivated by the prospect of payment or by concern that they would be letting down their clinician if they did not register.

Conclusions: There are currently major projects within the United Kingdom to increase the number of patients on dementia registers and to further involvement in dementia research. This study, to the best of our knowledge, is the first to assess the motivations of patients and carers for joining a dementia research register in the United Kingdom, and the findings highlight the importance of altruistic motives.

Background: Mild cognitive impairment (MCI) is a common condition among elderly persons. Its early identification is important because MCI can be a precursor of dementia. Since physicians’ knowledge and preferences regarding MCI can be critical in its identification, this study assessed family physicians’ familiarity, knowledge, and preferences regarding help-seeking, diagnosis, and treatment options for MCI.

Method: A convenience sample of 197 family physicians working in one of the largest Health Maintenance Organizations (HMOs) in Israel completed a structured questionnaire. Familiarity, knowledge, and preferences regarding diagnosis, help-seeking, and treatment of MCI were assessed.

Results: The majority of the participants had heard about MCI but a third of those familiar with the term reported knowing almost nothing about it. Participants’ objective knowledge was good regarding several causes of MCI, but 70% reported it to be caused by normal aging. Help-seeking and treatment preferences corresponded with the literature on MCI.

Conclusion: Our findings stress the need to broaden the understanding of primary care physicians’ knowledge and preferences regarding MCI. This research can guide in developing continuous education programs to strengthen areas and groups of physicians reporting low knowledge.

Background: The aim of this study was to assess the specificities of the Mini-Cog, the Clock Drawing Test (CDT), and the Mini-Mental State Examination (MMSE) against depression and healthy controls in a German Memory Clinic. Furthermore, we analyzed the specificities of all three screening instruments in dependence of actual depression severity.

Methods: Data from 142 depressed elderly, 438 dementia patients, and 64 healthy controls were retrospectively analyzed. The CDT and an extraction of the three-item recall of the MMSE were used to constitute the Mini-Cog algorithm. Depression severity was rated by either the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) depending on the age of the patients.

Results: The Mini-Cog achieved a specificity of 79.6% against depressed elderly and 100.0% against healthy subjects (p < 0.001). Similarly, the specificities of the CDT (83.8%) and MMSE (92.3% at a cut-off ≤24 and 90.8% at ≤25, respectively) against healthy subjects were significantly higher than the specificities against depressed patients (each p < 0.05). Concerning the depressed patients, the MMSE demonstrated significant higher specificity than the Mini-Cog and the CDT, but also showed the lowest sensitivity for the detection of dementia. Surprisingly, the depression severity had no effect on the specificity of the Mini-Cog and the CDT, only the MMSE was susceptible for the depression severity.

Conclusion: Although the MMSE showed higher specificities, the weighting between the sensitivities and specificities in all tests prove again the Mini-Cog as a short, valid, and sensitive screening tool.

Background: Persons with dementia frequently present behavioral and psychological symptoms as well as delirium. However, the association between these has received little attention from researchers and current knowledge in this area is limited. The purpose of this study was to examine the relation between delirium and behavioral symptoms of dementia (BSD).

Methods: Participants were 155 persons with a diagnosis of dementia, 109 (70.3%) of whom were found delirious according to the Confusion Assessment Method. BSD were assessed using the Nursing Home Behavior Problem Scale.

Results: Participants with delirium presented significantly more BSD than participants without delirium. More specifically, they presented more wandering/trying to leave, sleep problems, and irrational behavior after controlling for cognitive problems and use of antipsychotics and benzodiazepines. Most relationships between participant characteristics and BSD did not differ according to the presence or absence of delirium, but some variables, notably sleep problems, were more strongly associated to BSD in persons with delirium.

Conclusions: Although correlates of BSD in persons with delirium superimposed on dementia are generally similar to those in persons with dementia alone, delirium is associated with a higher level of BSD. Results of this study have practical implications for the detection of delirium superimposed on dementia, the management of behavioral disturbances in patients with delirium, and caregiver burden.

Background: Olfactory dysfunction, impaired smell identification in particular, is known as a diagnostic and a marker of conversion in Alzheimer's disease (AD). We aimed to evaluate the associations of olfactory identification impairments with cognition, illness severity, and progression in AD patients.

Methods: Fifty-seven outpatients with late onset mild to moderate AD and 24 elderly non-demented controls (NDC) were assessed, at baseline and after three months, for Mini-Mental State Examination (MMSE), University of Pennsylvania Smell Identification Test (UPSIT), and Bristol Activities of Daily Living and Neuropsychiatry Inventory. AD participants were classified as Rapid Cognitive Decliners (RCD) defined on a priori with a loss of ≥2 points in MMSE within the previous six months.

Results: AD participants had lower olfactory scores than NDC. RCD had lower olfaction scores compared with Non-Rapid Cognitive Decliners (NRCD). Although the baseline UPSIT scores were associated with baseline MMSE scores, it did not interact significantly with change in MMSE over the follow-up period. Using a median split for olfactory scores, the AD participants were classified as Rapid Olfactory Progressors (ROP) (UPSIT ≤ 15) and Slow Olfactory Progressors correlating significantly with RCD/NRCD groups. The ROP group with higher olfactory impairment indicated more symptomatic illness or severity, i.e. lower cognition, higher functional dependence, and presence of behavioral symptoms.

Conclusions: Our study supports association of smell identification function with cognition and its utility as an adjunct clinical measure to assess severity in AD. Further work, including larger longitudinal studies, is needed to explore its value in predicting AD progression.

Background: Anxiety and depression contribute to morbidity in elderly adults and may be associated with diet. We investigated the association between diet and psychological distress as a marker for depression.

Methods: Dietary patterns were defined by factor analysis or the Mediterranean Diet Score (MDS); depression and anxiety were assessed 12 years later. A total of 8,660 generally healthy men and women born in Australia and aged 50–69 years from the Melbourne Collaborative Cohort Study were included. At baseline (1990–1994), diet (food frequency questionnaire), education, Socio-Economic Indexes for Areas (SEIFA) – Index of Relative Socio-economic Disadvantage, medication use, social engagement, physical activity, smoking status, alcohol use, and health conditions were assessed; at follow-up (2003–2007), psychological distress was assessed using the Kessler Psychological Distress Scale (K10). Logistic regression was used to identify associations between diet and a K10 score ≥20, indicative of psychological distress.

Results: The MDS was inversely associated with psychological distress, with the odds ratio in the top-scoring group relative to the lowest scoring group being 0.72 (95% confidence interval = 0.54–0.95). Stronger adherence to a traditional Australian-style eating pattern was also associated with a lower K10 score at follow-up, with the odds ratio for having a K10 score indicative of psychological distress for the top 20% of adherence to this pattern relative to the lowest being 0.61 (95% confidence interval = 0.40–0.91).

Conclusions: A Mediterranean-style diet was associated with less psychological distress, possibly through provision of a healthy nutrient profile. The Australian dietary pattern, which included some foods high in fat and sugar content along with whole foods, also showed a weak inverse association. Adherence to this pattern may reflect a feeling of belonging to the community associated with less psychological distress.

Background: Effectiveness of educational interventions targeted at improving delirium care is limited by implementation barriers. Studying factors which shape learning needs can overcome these knowledge transfer barriers. This in-depth qualitative study explores learning needs of hospital staff relating to care needs of the confused older patients.

Methods: Fifteen research participants from across the healthcare spectrum working within an acute care setting were interviewed. Five focus groups were undertaken with patients, carers, and mental health specialists. A Grounded Theory methodology was adopted and data were analyzed thematically in parallel to collection until theoretical saturation was reached.

Results: Eight categories of practice gap emerged: ownership of the confused patient, negative attitudes, lack of understanding of how frightened the patient is in hospital, carer partnerships, person-centered care, communication, recognition of cognitive impairment and specific clinical needs (e.g. capacity assessments). Conceptually, the learning needs were found to be hierarchically related. Moreover, a vicious circle relating to the core learning needs of ownership, attitudes and patient's fear emerged. A patient with delirium may be frightened in an alien environment and then negatively labeled by staff who subsequently wish for their removal, thereby worsening the patient's fear.

Discussion: These findings reconceptualize delirium education approaches suggesting a need to focus interventions on core level practice gaps. This fresh perspective on education, away from disease-based delirium knowledge toward work-based patient, team and practice knowledge, could lead to more effective educational strategies to improve delirium care.

Background: Acceptability and fidelity assessments are an integral part of research, although few published trials comment on these processes in detail.

Methods: We designed a randomized controlled trial (RCT) to identify the benefits of a cognition-focused intervention for older adults with mild cognitive impairment. Participants completed a six-item feedback questionnaire identifying level of satisfaction with their allocated intervention; this formed the acceptability assessment. Audio recordings of all sessions were reviewed and systematically assessed and rated for consistency of delivery (fidelity assessment).

Results: Mean attendance (standard deviation) was 8.1 sessions (2.8) for the cognitive activity (CA) group and 8.4 (2.6) for the control general education group. There were no differences between groups regarding clarity and interest, willingness to attend the program in the community and pay a fee. Both groups reported the interventions to be relevant to their needs; however, this was rated more highly by the CA group (p < 0.01). There was high adherence to delivery of program content across both groups, yielding consistency scores above 95%.

Conclusion: This study illustrates a systematic approach to assess acceptability and fidelity. The results show that the intervention was well received and met the needs of all participants. The manualized structure of the sessions facilitated the systematic implementation and reproducibility of the interventions. Acceptability and fidelity assessments have implications for the validity of assumptions made regarding trial outcomes and should therefore be included as standard process in RCTs.

Background: Physicians often miss diagnosis of mild cognitive impairment (MCI) or early dementia and screening measures can be insensitive to very mild impairments. Other cognitive assessments may take too much time or be frustrating to seniors. This study examined the ability of an audio-recorded scale, developed in Australia, to detect MCI or mild Alzheimer's disease (AD) and compared cognitive domain-specific performance on the audio-recorded scale to in-person battery and common cognitive screens.

Method: Seventy-six patients from the Mount Sinai Alzheimer's Disease Research Center were recruited. Patients were aged 75 years or older, with clinical diagnosis of AD or MCI (n = 51) or normal control (n = 25). Participants underwent in-person neuropsychological testing followed by testing with the audio-recorded cognitive screen (ARCS).

Results: ARCS provided better discrimination between normal and impaired elderly individuals than either the Mini-Mental State Examination or the clock drawing test. The in-person battery and ARCS analogous variables were significantly correlated, most in the 0.4 to 0.7 range, including verbal memory, executive function/attention, naming, and verbal fluency. The area under the curve generated from the receiver operating characteristic curves indicated high and equivalent discrimination for ARCS and the in-person battery (0.972 vs. 0.988; p = 0.23).

Conclusion: The ARCS demonstrated better discrimination between normal controls and those with mild deficits than typical screening measures. Performance on cognitive domains within the ARCS was well correlated with the in-person battery. Completion of the ARCS was accomplished despite mild difficulty hearing the instructions even in very elderly participants, indicating that it may be a useful measure in primary care settings.