Are antidementia drugs associated with reduced mortality after a hospital emergency admission in the population with dementia aged 65 years and older?

INTRODUCTION: People with dementia experience poor outcomes after hospital admission, with mortality being particularly high. There is no cure for dementia; antidementia medications have been shown to improve cognition and function, but their effect on mortality in real-world settings is little known. This study examines associations between treatment with antidementia medication and mortality in older people with dementia after an emergency admission. METHODS: The design is a retrospective cohort study of people aged ≥65 years, with a diagnosis of dementia and an emergency hospital admission between 01/01/2010 and 31/12/2016. Two classes of antidementia medication were considered: the acetylcholinesterase inhibitors and memantine. Mortality was examined using a Cox proportional hazards model with time-varying covariates for the prescribing of antidementia medication before or on admission and during one-year follow-up, adjusted for demographics, comorbidity, and community prescribing including anticholinergic burden. Propensity score analysis was examined for treatment selection bias. RESULTS: There were 9142 patients with known dementia included in this study, of which 45.0% (n = 4110) received an antidementia medication before or on admission; 31.3% (n = 2864) were prescribed one of the acetylcholinesterase inhibitors, 8.7% (n = 798) memantine, and 4.9% (n = 448) both. 32.9% (n = 1352) of these patients died in the year after admission, compared to 42.7% (n = 2148) of those with no antidementia medication on admission. The Cox model showed a significant reduction in mortality in patients treated with acetylcholinesterase inhibitors (hazard ratio [HR] = 0.78, 95% CI 0.72-0.85) or memantine (HR = 0.75, 95% CI 0.66-0.86) or both (HR = 0.76, 95% CI 0.68-0.94). Sensitivity analysis by propensity score matching confirmed the associations between antidementia prescribing and reduced mortality. DISCUSSION: Treatment with antidementia medication is associated with a reduction in risk of death in the year after an emergency hospital admission. Further research is required to determine if there is a causal relationship between treatment and mortality, and whether "symptomatic" therapy for dementia does have a disease-modifying effect.

Identifying care-home residents in routine healthcare datasets: a diagnostic test accuracy study of five methods.

Background: there is no established method to identify care-home residents in routine healthcare datasets. Methods matching patient's addresses to known care-home addresses have been proposed in the UK, but few have been formally evaluated. Study design: prospective diagnostic test accuracy study. Methods: four independent samples of 5,000 addresses from Community Health Index (CHI) population registers were sampled for two NHS Scotland Health Boards on 1 April 2017, with one sample of adults aged ≥65 years and one of all residents. To derive the reference standard, all 20,000 addresses were manually adjudicated as 'care-home address' or not. The performance of five methods (NHS Scotland assigned CHI Institution Flag, exact address matching, postcode matching, Phonics and Markov) was evaluated compared to the reference standard. Results: the CHI Institution Flag had a high PPV 97-99% in all four test sets, but poorer sensitivity 55-89%. Exact address matching failed in every case. Postcode matching had higher sensitivity than the CHI flag 78-90%, but worse PPV 77-85%. Area under the receiver operating curve values for Phonics and Markov scores were 0.86-0.95 and 0.93-0.98, respectively. Phonics score with cut-off ≥13 had PPV 92-97% with sensitivity 72-87%. Markov PPVs were 90-95% with sensitivity 69-90% with cut-off ≥29.6. Conclusions: more complex address matching methods greatly improve identification compared to the existing NHS Scotland flag or postcode matching, although no method achieved both sensitivity and positive predictive value > 95%. Choice of method and cut-offs will be determined by the specific needs of researchers and practitioners.

Living at home after emergency hospital admission: prospective cohort study in older adults with and without cognitive spectrum disorder.

BACKGROUND: Cognitive spectrum disorders (CSDs) are common in hospitalised older adults and associated with adverse outcomes. Their association with the maintenance of independent living has not been established. The aim was to establish the role of CSDs on the likelihood of living at home 30 days after discharge or being newly admitted to a care home. METHODS: A prospective cohort study with routine data linkage was conducted based on admissions data from the acute medical unit of a district general hospital in Scotland. 5570 people aged ≥ 65 years admitted from a private residence who survived to discharge and received the Older Persons Routine Acute Assessment (OPRAA) during an incident emergency medical admission were included. The outcome measures were living at home, defined as a private residential address, 30 days after discharge and new care home admission at hospital discharge. Outcomes were ascertained through linkage to routine data sources. RESULTS: Of the 5570 individuals admitted from a private residence who survived to discharge, those without a CSD were more likely to be living at home at 30 days than those with a CSD (93.4% versus 81.7%; difference 11.7%, 95%CI 9.7-13.8%). New discharge to a care home affected 236 (4.2%) of the cohort, 181 (76.7%) of whom had a CSD. Logistic regression modelling identified that all four CSD categories were associated with a reduced likelihood of living at home and an increased likelihood of discharge to a care home. Those with delirium superimposed on dementia were the least likely to be living at home (OR 0.25), followed by those with dementia (OR 0.43), then unspecified cognitive impairment (OR 0.55) and finally delirium (OR 0.57). CONCLUSIONS: Individuals with a CSD are at significantly increased risk of not returning home after hospitalisation, and those with CSDs account for the majority of new admissions to care homes on discharge. Individuals with delirium superimposed on dementia are the most affected. We need to understand how to configure and deliver healthcare services to enable older people to remain as independent as possible for as long as possible and to ensure transitions of care are managed supportively.

Mortality in people with dementia, delirium, and unspecified cognitive impairment in the general hospital: prospective cohort study of 6,724 patients with 2 years follow-up.

PURPOSE: Cognitive impairment is common in older people admitted to hospital, but the outcomes are generally poorly understood, and previous research has shown inconsistent associations with mortality depending on the type of cognitive impairment examined and duration of follow-up. This study examines mortality in older people with any cognitive impairment during acute hospital admission. PATIENTS AND METHODS: Prospective cohort of 6,724 people aged ≥65 years with a structured cognitive assessment on acute admission were included in this study. Cognitive spectrum disorder (CSD) was defined as delirium alone, known dementia alone, delirium superimposed on known dementia, or unspecified cognitive impairment. Mortality associated with different types of CSD was examined using a non-proportional hazards model with 2-year follow-up. RESULTS: On admission, 35.4% of patients had CSD, of which 52.6% died within 2 years. After adjustment for demographics and comorbidity, delirium alone was associated with increased mortality in the 6 months post-admission (HR =1.45, 95% CI 1.28-1.65) and again after 1 year (HR =1.44, 95% CI 1.17-1.77). Patients with known dementia (alone or with superimposed delirium) had increased mortality only after 3 months from admission (HR =1.85, 95% CI 1.56-2.18 and HR =1.80, 95% CI 1.52-2.14) compared with patients with unspecified cognitive impairment after 6 months (HR =1.55, 95% CI 1.21-1.99). Similar but partially attenuated associations were seen after adjustment for functional ability. CONCLUSION: Mortality post-admission is high in older people with CSD. Immediate risk is highest in those with delirium, while dementia or unspecified cognitive impairment is associated with medium- to long-term risk. These findings suggest that individuals without dementia who develop delirium are more seriously ill (have required a larger acute insult in order to precipitate delirium) than those with pre-existing brain pathology (dementia). Further research to explain the mortality patterns observed is required in order to translate the findings into clinical care.

Epidemiology and outcomes of people with dementia, delirium, and unspecified cognitive impairment in the general hospital: prospective cohort study of 10,014 admissions.

BACKGROUND: Cognitive impairment of various kinds is common in older people admitted to hospital, but previous research has usually focused on single conditions in highly-selected groups and has rarely examined associations with outcomes. This study examined prevalence and outcomes of cognitive impairment in a large unselected cohort of people aged 65+ with an emergency medical admission. METHODS: Between January 1, 2012, and June 30, 2013, admissions to a single general hospital acute medical unit aged 65+ underwent a structured specialist nurse assessment (n = 10,014). We defined 'cognitive spectrum disorder' (CSD) as any combination of delirium, known dementia, or Abbreviated Mental Test (AMT) score < 8/10. Routine data for length of stay (LOS), mortality, and readmission were linked to examine associations with outcomes. RESULTS: A CSD was present in 38.5% of all patients admitted aged over 65, and in more than half of those aged over 85. Overall, 16.7% of older people admitted had delirium alone, 7.9% delirium superimposed on known dementia, 9.4% known dementia alone, and 4.5% unspecified cognitive impairment (AMT score < 8/10, no delirium, no known dementia). Of those with known dementia, 45.8% had delirium superimposed. Outcomes were worse in those with CSD compared to those without - LOS 25.0 vs. 11.8 days, 30-day mortality 13.6% vs. 9.0%, 1-year mortality 40.0% vs. 26.0%, 1-year death or readmission 62.4% vs. 51.5% (all P < 0.01). There was relatively little difference by CSD type, although people with delirium superimposed on dementia had the longest LOS, and people with dementia the worst mortality at 1 year. CONCLUSIONS: CSD is common in older inpatients and associated with considerably worse outcomes, with little variation between different types of CSD. Healthcare systems should systematically identify and develop care pathways for older people with CSD admitted as medical emergencies, and avoid only focusing on condition-specific pathways such as those for dementia or delirium alone.

Predicting discharge to institutional long-term care following acute hospitalisation: a systematic review and meta-analysis.

Background: moving into long-term institutional care is a significant life event for any individual. Predictors of institutional care admission from community-dwellers and people with dementia have been described, but those from the acute hospital setting have not been systematically reviewed. Our aim was to establish predictive factors for discharge to institutional care following acute hospitalisation. Methods: we registered and conducted a systematic review (PROSPERO: CRD42015023497). We searched MEDLINE; EMBASE and CINAHL Plus in September 2015. We included observational studies of patients admitted directly to long-term institutional care following acute hospitalisation where factors associated with institutionalisation were reported. Results: from 9,176 records, we included 23 studies (n = 354,985 participants). Studies were heterogeneous, with the proportions discharged to a care home 3-77% (median 15%). Eleven studies (n = 12,642), of moderate to low quality, were included in the quantitative synthesis. The need for institutional long-term care was associated with age (pooled odds ratio (OR) 1.02, 95% confidence intervals (CI): 1.00-1.04), female sex (pooled OR 1.41, 95% CI: 1.03-1.92), dementia (pooled OR 2.14, 95% CI: 1.24-3.70) and functional dependency (pooled OR 2.06, 95% CI: 1.58-2.69). Conclusions: discharge to long-term institutional care following acute hospitalisation is common, but current data do not allow prediction of who will make this transition. Potentially important predictors evaluated in community cohorts have not been examined in hospitalised cohorts. Understanding these predictors could help identify individuals at risk early in their admission, and support them in this transition or potentially intervene to reduce their risk.

Comorbidity and polypharmacy in people with dementia: insights from a large, population-based cross-sectional analysis of primary care data.

Background: The care of older people with dementia is often complicated by physical comorbidity and polypharmacy, but the extent and patterns of these have not been well described. This paper reports analysis of these factors within a large, cross-sectional primary care data set. Methods: Data were extracted for 291,169 people aged 65 years or older registered with 314 general practices in the UK, of whom 10,258 had an electronically recorded dementia diagnosis. Differences in the number and type of 32 physical conditions and the number of repeat prescriptions in those with and without dementia were examined. Age­gender standardised rates were used to calculate odds ratios (ORs) of physical comorbidity and polypharmacy. Results: People with dementia, after controlling for age and sex, had on average more physical conditions than controls (mean number of conditions 2.9 versus 2.4; P < 0.001) and were on more repeat medication (mean number of repeats 5.4 versus 4.2; P < 0.001). Those with dementia were more likely to have 5 or more physical conditions (age­sex standardised OR [sOR] 1.42, 95% confidence interval (CI) 1.35­1.50; P < 0.001) and were also more likely to be on 5 or more (sOR 1.46; 95% CI 1.40­1.52; P < 0.001) or 10 or more repeat prescriptions (sOR 2.01; 95% CI 1.90­2.12; P < 0.001). Conclusions: People with dementia have a higher burden of comorbid physical disease and polypharmacy than those without dementia, even after accounting for age and sex differences. Such complex needs require an integrated response from general health professionals and multidisciplinary dementia specialists.

Outcomes measures in a decade of dementia and mild cognitive impairment trials.

BACKGROUND: In a research study, to give a comprehensive evaluation of the impact of interventions, the outcome measures should reflect the lived experience of the condition. In dementia studies, this necessitates the use of outcome measures which capture the range of disease effects, not limited to cognitive functioning. In particular, assessing the functional impact of cognitive impairment is recommended by regulatory authorities, but there is no consensus on the optimal approach for outcome assessment in dementia research. Our aim was to describe the outcome measures used in dementia and mild cognitive impairment (MCI) intervention studies, with particular interest in those evaluating patient-centred outcomes of functional performance and quality of life. METHODS: We performed a focused review of the literature with multiple embedded checks of internal and external validity. We used the Cochrane Dementia and Cognitive Improvement Group's register of dementia studies, ALOIS. ALOIS was searched to obtain records of all registered dementia and MCI intervention studies over a 10-year period (2004-2014). We included both published and unpublished materials. Outcomes were categorised as cognitive, functional, quality of life, mood, behaviour, global/disease severity and institutionalisation. RESULTS: From an initial return of 3271 records, we included a total of 805 records, including 676 dementia trial records and 129 MCI trial records. Of these, 78 % (630) originated from peer-reviewed publications and 60 % (487) reported results of pharmacological interventions. Cognitive outcomes were reported in 70 % (563), in contrast with 29 % (237) reporting measures of functional performance and only 13 % (102) reporting quality of life measures. We identified significant heterogeneity in the tools used to capture these outcomes, with frequent use of non-standardised tests. CONCLUSIONS: This focus on cognitive performance questions the extent to which intervention studies for dementia are evaluating outcome measures which are relevant to individual patients and their carers. The heterogeneity in measures, use of bespoke tools and poor descriptions of test strategy all support the need for a more standardised approach to the conduct and reporting of outcomes assessments.

Spotlight on Scotland: Assets and Opportunities for Aging Research in a Shifting Sociopolitical Landscape.

Scotland is a small nation, yet it leads the field in key areas of aging research. With the creation of a devolved government with authority over health and social services, the country has witnessed practice and policy developments that offer distinctive opportunities for innovative research. With multidisciplinary groups of internationally recognized researchers, Scotland is able to take advantage of a unique set of opportunities for aging research: a well-profiled population brings opportunities in population data and linkage to understand people's interactions with health, social care, and other public services; while research on technology and telecare is a distinctive area where Scotland is recognized internationally for using technology to develop effective, high-quality and well-accepted services at relatively low financial cost. The paper also considers free personal care for older people and the national dementia strategy in Scotland. The potential to evaluate the impact of free personal care will provide valuable information for other global health and social care systems. Exploring the impact of the national dementia strategy is another unique area of research that can advance understanding in relation to quality of life and the development of services. The paper concludes that, while Scotland benefits from unique opportunities for progressive public policy and innovative aging research that will provide valuable lessons at the forefront of a globally aging population, the challenges associated with an aging population and increasing cultural diversity must be acknowledged and addressed to ensure that the vision of equality and social justice for all is realized.

Expert opinion on the management of pain in hospitalised older patients with cognitive impairment: a mixed methods analysis of a national survey.

BACKGROUND: Hospitalised older patients are complex. Comorbidity and polypharmacy complicate frailty. Significant numbers have dementia and/or cognitive impairment. Pain is highly prevalent. The evidence base for pain management in cognitively impaired individuals is sparse due to methodological issues. A wealth of expert opinion is recognised potentially providing a useful evidence base for guiding clinical practice. The study aimed to gather expert opinion on pain management in cognitively impaired hospitalised older people. METHODS: Consultant Geriatricians listed as dementia leads in the National Dementia Audit were contacted electronically and invited to respond. The questionnaire sought information on their role, confidence and approach to pain management in cognitively impaired hospitalised patients. Responses were analysed using a mixed methods approach. RESULTS: Respondents considered themselves very confident in the clinical field. Awareness of potential to do harm was highly evident. Unequivocally responses suggested paracetamol is safe and should be first choice analgesic, newer opiates should be used preferentially in renal impairment and nefopam is unsafe. A grading of the safety profile of specific medications became apparent, prompting requirement for further evaluation and holistic assessment. CONCLUSION: The lack of consensus reached highlights the complexity of this clinical field. The use of paracetamol first line, newer opiates in renal impairment and avoidance of nefopam are immediately transferrable to clinical practice. Further review, evaluation and comparison of the risks associated with other specific analgesics are necessary before a comprehensive clinical guideline can be produced.

Experience and opinions on post-graduate dementia training in the UK: a survey of selected consultant geriatricians.

INTRODUCTION: people with dementia are more likely to come into contact with a geriatrician than any other hospital specialty. Whilst it is known that there are some geriatricians with a special interest in dementia, it is unclear how this group of clinicians gained experience, and what their opinions are on current training. METHODS: we obtained a list of geriatricians known to have an interest in dementia care (known as dementia champions) from the British Geriatric Society Dementia and Similar Disorders Special Interest Group. We contacted 100 'dementia champions' with an invitation to respond to a questionnaire relating to their role, experience and opinions on current training in dementia within geriatric medicine. RESULTS: fifty-five geriatricians responded. Ninety-one per cent were consultant physicians, and 71% were not involved in outpatient diagnostic services. Fifty-six per cent reported that their experience was via clinical attachments with old age psychiatry, and 47% regarded themselves as 'self-taught'. The majority felt that current training was inadequate with a need for more structure and time spent on attachments, less geographical variation, more training at undergraduate level and throughout other specialties and better collaboration with psychiatry. DISCUSSION: this is the first survey of the views of geriatricians leading on dementia care in acute hospitals within the UK. It gives a useful insight into how they have gained their own experience, and their opinions on how training may be improved. Equipped with the right training and expertise in diagnosis and management of dementia perhaps geriatricians may feel more confident in taking a lead in dementia care.

Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011.

BACKGROUND: Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact. METHODS: Segmented regression time-series analysis 2001-2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing. RESULTS: The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI -6.6 to -5.2) and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs. CONCLUSIONS: The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling, antipsychotic prescribing in dementia in Scotland remains unacceptably high.

Improving recognition of delirium in clinical practice: a call for action.

BACKGROUND: The purpose of this correspondence article is to report opinion amongst experts in the delirium field as to why, despite on-going training for all health professionals, delirium continues to be under recognised. Consensus was obtained by means of two conference workshops and an online survey of members of the European Delirium Association.Major barriers to recognition at an individual level include ignorance about the benefit of treating delirium. At an organisational level, reflecting socio-cultural attitudes, barriers include a low strategic and financial priority and the fact that delirium is an orphan condition falling between specialties.

Rising incidence of pediatric inflammatory bowel disease in Scotland.

BACKGROUND: An accurate indication of the changing incidence of pediatric inflammatory bowel disease (PIBD) within a population is useful in understanding concurrent etiological factors. We aimed to compare the current incidence and other demographic attributes of PIBD in the Scottish population to previous data. METHODS: A national cohort of prospectively and retrospectively acquired incident cases of PIBD diagnosed less than 16 years old in pediatric services in Scotland was captured for the period 2003-2008; historical Scottish data were used for comparison (1990-1995). Age/sex-adjusted incidences were calculated and statistical comparisons made using Poisson regression. RESULTS: During the 2003-2008 study period 436 patients were diagnosed with PIBD in Scotland, giving an adjusted incidence of 7.82/100,000/year. The incidence of Crohn's disease (CD) was 4.75/100,000/year, ulcerative colitis (UC) 2.06/100,000/year, and inflammatory bowel disease-unclassified (IBDU) 1.01/100,000/year. Compared with data from 1990-1995 when 260 IBD patients were diagnosed, significant rises in the incidence of IBD (from 4.45/100,000/year, P < 0.0001), CD (from 2.86/100,000/year, P < 0.0001), and UC (from 1.59/100,000/year, P = 0.023) were seen. There was also a significant reduction in the median age at IBD diagnosis from 12.7 years to 11.9 years between the periods (P = 0.003), with a continued male preponderance. CONCLUSIONS: The number of Scottish children diagnosed with IBD continues to rise, with a statistically significant 76% increase since the mid-1990 s. Furthermore, PIBD is now being diagnosed at a younger age. The reason for this continued rise is not yet clear; however, new hypotheses regarding disease pathogenesis and other population trends may provide further insights in future years.

Regional variation on the presentation of Alzheimer's disease patients in memory clinics within Europe: data from the ICTUS study.

This study set out to describe the variations within Europe for Alzheimer's disease (AD) patients with regards to clinical and socio-demographic features, co-morbidities, drug treatment, and psychosocial care. 1,379 mild to moderate AD subjects from the ICTUS study were clustered into four geographic regions according to WHO-classification of European countries. Northern patients showed the mildest severity of dementia (MMSE: 21.6 +/- 3.7, p< 0.001), received the lowest rate of concomitant psychotropic drug treatment (24.3%, p< 0.001), and appeared to be healthier than patients in the rest of Europe. Western subjects were diagnosed earliest (0.5 +/- 0.9 month, p< 0.001), received the highest rate of formal care (45.0%, p< 0.001), and had the highest rates of antidementia drug treatment (60.4%, p< 0.001). Southern subjects had the shortest education period (5.6 +/- 4.0, p< 0.001), the most severe cognitive decline in MMSE: 19.8 +/- 4.0, $p<$ 0.001 and ADAScog: 24.2 9.6, p< 0.001 and received less antidementia drug treatment (37.6%; p< 0.001), lived more often with their caregivers (74.4%, p< 0.001), and had the highest caregiver burden (22.6 +/- 15.2, p=0.049). Eastern AD subjects received more concomitant psychopharmacological drugs (68.6%, p< 0.001), caregivers were more often different (18.6%, p< 0.001) from spouse or offspring, caregiver burden was lowest (18.7 +/- 12.4, p=0.049), nearly all subjects received only informal care (95.7%, p< 0.001) and were affected more by co-morbidities. Overall, these data show differences in socio-demographic and clinical characteristics between AD patients from four European geographical regions. The presentation and management of AD in Europe appears to differ according to European regions and likely reflects differences in cultural factors and health politics.

Does cognitive impairment influence burden in caregivers of patients with Alzheimer's disease?

Alzheimer's disease (AD) is characterized by a progressive deterioration of various cognitive and behavioral abilities, and it also has a health impact on the patients' caregiver. Our aim was to determine the patient (and to a lesser extent the caregiver) characteristics that contribute most to the caregiver burden. We used the baseline data from the ICTUS study, a European longitudinal cohort of patients with mild to moderate AD. Data from 1091 patients and their caregivers was used for analysis. Three principal components analyses were performed on variables from the domains of cognition, neuropsychiatric symptoms, and daily function using the MMSE plus the ADAS-Cog, NPI, and IADL subscores, respectively. These were followed by a stepwise logistic regression to identify patient characteristics which best predict caregiver burden. The regression model (R2 = 0.35, p < 0.001) shows that the best explanatory variables are: 1) neuropsychiatric symptoms (NPI); 2) difficulties in the IADL; 3) time taken by caregiving; 4) demographic variables such as caregiver's age and patient sex; and 5) severity of cognitive impairment. In conclusion, our results demonstrate that although the strongest determinant of the caregiver burden is behavioral disturbance, the impact of the degree of cognitive impairment on burden is also significant.

Multi-center comparison of medial temporal atrophy in patients with Alzheimer's disease--data from the ICTUS study.

OBJECTIVE: To study multi-center variability of medial temporal lobe atrophy (MTA) in patients with Alzheimer's disease (AD) recruited in a European observational study of AD. METHODS: 117 mild to moderate AD patients from 5 European centers (Amsterdam, The Netherlands; Brescia and Genova, Italy; Mannheim, Germany; Pamplona, Spain) had magnetic resonance imaging scans performed as part of the routine diagnostic examination. MTA was assessed with the visual Scheltens scale. RESULTS: AD patients from Brescia, Genova, Pamplona, and Mannheim had a mean 32% prevalence of no or borderline MTA vs. 62% of patients from Amsterdam (p = 0.002 for the difference between Amsterdam and all the other centers). The peculiar distribution of MTA in the Amsterdam patients may be attributable to younger age (70.7 +/- 8.4 vs. 75.3 +/- 6.8 years, p = 0.002), milder dementia severity (score 0.5 on the clinical dementia rating scale: 52 vs. 23%, p = 0.003), and less frequent depression (14 vs. 49%, p < 0.0005 in Amsterdam vs. all the other centers, respectively). CONCLUSION: Patients with probable AD recruited in different centers of Europe generally have similar MTA distribution, even if peculiar demographic and clinical findings might explain occasional differences. These results have implications for clinical trials in AD with biological markers as outcome measures.

Predictive value of rapid decline in mini mental state examination in clinical practice for prognosis in Alzheimer's disease.

BACKGROUND: Given the poorer prognosis of Alzheimer's disease (AD) patients with rapid cognitive decline (RCD), there is a need for a clinical assessment tool to detect these patients. OBJECTIVE: To investigate if there is a Mini Mental State Examination (MMSE) threshold of decline during 6 months of follow-up which predicts a worse disease progression at the 2-year follow-up. Then, to propose a feasible definition of RCD for routine clinical practice. METHODS: Data from 565 community-dwelling AD patients recruited in a multi-centre prospective observational study were assessed. All patients had MMSE scores between 10 and 26 at inclusion and were followed up 6-monthly using a standardised clinical assessment. Patients were classified as rapid and non-rapid decliners according to 2 MMSE decline thresholds tested: >or=3 points and >or=4 points for decline over the first 6 months of the study. Worse disease outcome was defined as attainment of 1 of 4 clinical end points 18 months later: institutionalisation, death, increased physical dependence or worsening of behavioural and psychological symptoms. RESULTS: 135 patients (23.9%) lost >or=3 points during the first 6 months of follow-up in the MMSE score and 77 patients (13.6%) lost >or=4 points. Patients with moderate disease and a loss of >or=4 points showed a significantly increased risk of mortality (HR = 5.6, 95% CI 2.0-15.9) and institutionalisation (HR = 3.8, 95% CI 1.8-8.1) at the 2-year follow-up. The same MMSE threshold was associated with a higher risk of physical decline (HR = 1.6, 95% CI 1.2-2.3). CONCLUSION: The loss of >or=4 points in MMSE during the first 6 months of follow-up seems to be a predictor of worse clinical course, and thus it could be used to define the category of AD patients presenting a RCD.

The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium.

BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid, and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater by using visual rating scales. RESULTS: Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioral, and neuropsychological features of the European subjects were very similar to their U.S. counterparts. Three-dimensional T1-weighted MRI sequences were successfully performed on all subjects, and cerebrospinal fluid samples were obtained from 77%, 68%, and 83% of AD patients, MCI patients, and controls, respectively. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI patients (0.9, 0.8) to AD patients (2.3, 2.0), whereas mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US-ADNI subjects. CONCLUSIONS: Academic EADC centers can adopt the ADNI platform to enroll MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US-ADNI.