Cognitive Performance at Time of AD Diagnosis: A Clinically Augmented Register-Based Study.

We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer's disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010-2013 (aged 60-81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.

Education-Based Cutoffs for Cognitive Screening of Alzheimer's Disease.

INTRODUCTION: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer's disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. METHODS: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden's J was calculated for the overall performance and accuracy of each of the measures. RESULTS: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. CONCLUSIONS: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.

Monetary value of informal caregiving in dementia from a societal perspective.

BACKGROUND: Dementia is a condition which results in a high cost of care, a significant proportion of which is the cost associated with informal care. In previous studies, informal caregiving has been challenging to assess due to difficulties in estimating the true time spent on caregiving work and how to value caregivers' time. The aim of this study was to compare the costs of dementia among patients living alone and among those living with a caregiver to show the monetary value of informal caregiving from a societal perspective. METHODS: Data from our four dementia trials using the same measures were combined, allowing the inclusion of 604 participants. Participants were followed up for 2 years or until death for their use of health and social services. Use of all services was retrieved from medical/social records. We also included the costs of lost productivity of those caregivers who were not retired. RESULTS: The total mean cost of services and lost productivity was €22,068/person-year (pyrs). Participants living alone had a mean cost of €45,156/pyrs, whereas those living with a spouse had a mean cost of €16,416/pyrs (mean cost ratio 2.99, 95% confidence interval 2.64-3.39). Participants living alone and having <15 Mini-Mental State Examination points had higher costs than people with dementia in institutional care. CONCLUSIONS: Detailed data of service use and characteristics of people with dementia showed that from a societal perspective, living alone is a very strong determinant of service use in dementia. Informal caregivers do invaluable work for society.

Relationship of Neuropsychiatric Symptoms with Falls in Alzheimer's Disease - Does Exercise Modify the Risk?

OBJECTIVES: To explore how neuropsychiatric symptoms (NPS) are associated with number of falls and how exercise modifies the risk of falling in community-dwelling people with Alzheimer's disease (AD) and NPS. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Community. PARTICIPANTS: Community-dwelling individuals with AD (N=210) who completed the Neuropsychiatric Inventory (NPI) (N = 179). INTERVENTION: Participants were randomized into 3 groups: group-based exercise (4-hour sessions with approximately 1 hour of training) and tailored home-based exercise (1 hour of training) twice a week for 1 year and a control group receiving usual community care. In this secondary analysis, we merged the home-based and group-based exercise groups and compared this group with the control group. MEASUREMENTS: NPS were measured using the NPI at baseline, and spousal caregivers recorded falls in daily fall diaries during 1 year of follow-up. RESULTS: The number of falls increased linearly with NPI score in the control group. Fall rates were 1.48 (95% confidence interval (CI)=1.26-1.73) per person-year in the intervention group and 2.87 (95% CI=2.43-3.35) in the control group. Adjusted for age, sex, Mini-Mental State Examination (MMSE) score, and Short Physical Performance Battery (SPPB) score, incidence rate ratio (IRR) was 0.48 (95% Cl=0.39-0.60, p < .001). Main effects for fall rate were significant for group (p < .001) and NPI total (p < .02); the interaction effect was also significant (p = .009) (adjusted for sex, age, MMSE score, SPPB score, and psychotropic medication use). CONCLUSION: Exercise may decrease the risk of falling in community-dwelling individuals with AD and NPS. Future exercise trials should confirm this finding in participants with significant NPS. TRIAL REGISTRATION: ACTRN12608000037303. J Am Geriatr Soc 66:2377-2381, 2018.

Effect of Exercise on Drug-Related Falls Among Persons with Alzheimer's Disease: A Secondary Analysis of the FINALEX Study.

INTRODUCTION: No study has investigated how exercise modifies the effect of fall-related drugs (FRDs) on falls among people with Alzheimer's disease (AD). OBJECTIVE: The aim of this study was to investigate how exercise intervention and FRDs interact with fall risk among patients with AD. METHODS: In the FINALEX trial, community-dwelling persons with AD received either home-based or group-based exercise twice weekly for 1 year (n =129); the control group received normal care (n =65). The number of falls was based on spouses' fall diaries. We examined the incidence rate ratios (IRRs) for falls among both non-users and users of various FRDs (antihypertensives, psychotropics, drugs with anticholinergic properties [DAPs]) in both control and combined intervention groups. RESULTS: Between the intervention and control groups, there was no difference in the number of falls among those without antihypertensives or psychotropics. In the intervention group taking antihypertensives, the IRR was 0.5 falls/person-year (95% confidence interval [CI] 0.4-0.6), while in the control group, the IRR was 1.5 falls/person-year (95% CI 1.2-1.8) [p < 0.001 for group, p = 0.067 for medication, p < 0.001 for interaction]. Among patients using psychotropics, the intervention group had an IRR of 0.7 falls/person-year (95% CI 0.6-0.9), while the control group had an IRR of 2.0 falls/person-year (95% CI 1.6-2.5) [p < 0.001 for group, p = 0.071 for medication, p < 0.001 for interaction]. There was a significant difference in falls between the intervention and control groups not using DAPs (0.6, 95% CI 0.5-0.7; 1.2, 95% CI 1.0-1.4), and between the intervention and control groups using DAPs (1.1, 95% CI 0.8-1.3; 1.5, 95% CI 1.0-2.1) [p < 0.001 for group, p = 0.014 for medication, p  = 0.97 for interaction]. CONCLUSION: Exercise has the potential to decrease the risk for falls among people with AD using antihypertensives and psychotropics. TRIAL REGISTRATION: ACTRN12608000037303.

How Do Community-Dwelling Persons with Alzheimer Disease Fall? Falls in the FINALEX Study.

BACKGROUND: People with dementia are at high risk for falls. However, little is known of the features causing falls in Alzheimer disease (AD). Our aim was to investigate how participants with AD fall. METHODS: In the FINALEX (Finnish Alzheimer Disease Exercise Trial) study, participants' (n = 194) falls were followed up for 1 year by diaries kept by their spouses. RESULTS: The most common reason for falls (n = 355) was stumbling (n = 61). Of the falls, 123 led to injuries, 50 to emergency department visits, and 13 to fractures. The participants without falls (n = 103) were younger and had milder dementia than those with 1 (n = 34) or ≥2 falls (n = 57). Participants with a Mini Mental State Examination score of around 10 points were most prone to fall. In adjusted regression models, good nutritional status, good physical functioning, and use of antihypertensive medication (incident rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.54-0.85) protected against falls, whereas fall history (IRR 2.71, 95% CI 2.13-3.44), osteoarthritis, diabetes mellitus, chronic obstructive pulmonary disease, higher number of drugs, drugs with anticholinergic properties, psychotropics, and opioids (IRR 4.27, 95% CI 2.92-6.24) were risk factors for falls. CONCLUSIONS: Our study provides a detailed account on how and why people with AD fall, suggesting several risk and protective factors.

Potentially severe drug-drug interactions among older people and associations in assisted living facilities in Finland: a cross-sectional study.

OBJECTIVE: This study aims to assess potentially severe class D drug-drug interactions (DDDIs) in residents 65 years or older in assisted living facilities with the use of a Swedish and Finnish drug-drug interaction database (SFINX). DESIGN: A cross-sectional study of residents in assisted living facilities in Helsinki, Finland. SETTING: A total of 1327 residents were assessed in this study. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and DDDIs were coded according to the SFINX. MAIN OUTCOME MEASURES: Prevalence of DDDIs, associated factors and 3-year mortality among residents. RESULTS: Of the participants (mean age was 82.7 years, 78.3% were females), 5.9% (N = 78) are at risk for DDDIs, with a total of 86 interactions. Participants with DDDIs had been prescribed a higher number of drugs (10.8 (SD 3.8) vs. 7.9 (SD 3.7), p < 0.001). A larger proportion of residents with DDDIs suffered from rheumatoid arthritis or osteoarthritis than those not exposed to DDDIs (24.7% vs. 15.4%, p = 0.030). The most frequent DDDIs were related to the concomitant use of potassium with amiloride (N = 12) or spironolactone (N = 12). Carbamazepine (N = 13) and methotrexate (N = 9) treatments were also frequently linked to DDDIs. During the follow-up, no differences in mortality emerged between the participants exposed to DDDIs and the participants not exposed to DDDIs. CONCLUSIONS: Of the residents in assisted living, 5.9% were exposed to DDDIs associated with the use of a higher number of drugs. Physicians should be trained to find safer alternatives to drugs associated with DDDIs. KEY POINTS Potentially severe, class D drug-drug interactions (DDDIs) have been defined in the SFINX database as clinically relevant drug interactions that should be avoided. • Of the residents in assisted living, 5.9% were exposed to DDDIs that were associated with the use of a higher number of drugs. • The most frequent DDDIs were related to the concomitant use of potassium with amiloride or spironolactone. Carbamazepine and methotrexate were also linked to DDDIs. • No difference in mortality was observed between residents exposed to DDDIs and residents not exposed to DDDIs.

Effects of Exercise on Functional Performance and Fall Rate in Subjects with Mild or Advanced Alzheimer's Disease: Secondary Analyses of a Randomized Controlled Study.

BACKGROUND: Exercise improves functional performance in subjects with dementia. However, whether the benefits of exercise are evident in all stages of dementia remains uncertain. This study examines how people in different stages of Alzheimer's disease (AD) benefit from exercise intervention in their physical functioning and risk of falling. METHODS: The present study is a subanalysis of a randomized controlled trial examining the effects of exercise intervention (twice a week for 12 months) in AD patients (n = 194). We studied the effects separately in participants with mild dementia and in participants with advanced dementia. RESULTS: In subjects with mild dementia, the deterioration in physical functioning was slower in the intervention group than in the controls. Changes in Functional Independence Measure at 12 months were -2.7 (95% CI -0.5 to -4.9) in the intervention group and -10.1 (95% CI -7.0 to -13.3) in the control group (p < 0.001). The exercise intervention proved effective in preventing falls among patients with advanced AD, with an incidence rate ratio of 0.47 (95% CI 0.37-0.60; p < 0.001). CONCLUSIONS: Regular exercise may slow the rate of functional deterioration in mild AD and reduce falls in patients suffering from advanced AD.

Effects of Exercise on Cognition: The Finnish Alzheimer Disease Exercise Trial: A Randomized, Controlled Trial.

OBJECTIVES: To examine whether a regular, long-term exercise program performed by individuals with Alzheimer's disease (AD) at home or as group-based exercise at an adult daycare center has beneficial effects on cognition; to examine secondary outcomes of a trial that has been published earlier. DESIGN: Randomized, controlled trial. SETTING: Community. PARTICIPANTS: Community-dwelling dyads (N = 210) of individuals with AD and their spousal caregivers randomized into three groups. INTERVENTION: Two types of intervention comprising customized home-based exercise (HE) and group-based exercise (GE), each twice a week for 1 year, were compared with a control group (CG) receiving usual community care. MEASUREMENTS: Cognitive function was measured using the Clock Drawing Test (CDT), Verbal Fluency (VF), Clinical Dementia Rating (CDR), and Mini-Mental State Examination (MMSE) at baseline and 3, 6, and 12 months of follow-up. RESULTS: Executive function, measured using CDT, improved in the HE group, and changes in the score were significantly better than those of the CG at 12 months (adjusted for age, sex, and CDR, P = .03). All groups deteriorated in VF and MMSE score during the intervention, and no significant differences between the groups were detected at 12-month follow-up when analyses were adjusted for age, sex, and CDR. CONCLUSION: Regular, long-term, customized HE improved the executive function of community-dwelling older people with memory disorders, but the effects were mild and were not observed in other domains of cognition.

Alzheimer's patients' spouses critiques of the support services.

Introduction. Caregiving families of patients with dementia are often reluctant to use support services. The aim of this study was to describe their subjective critiques of these services. Material and Methods. A cross-sectional questionnaire was sent to a random sample (N = 1943) of Alzheimer's patients' spouses in Finland with an open-ended question: "What kind of problems have you faced with the services?" Their responses were analyzed with thematic content analysis. Results. Of the responders identifying themselves as caregivers (N = 1386), 728 (mean age 77.8, 65.1% females) responded. Opinions could be divided into two categories: (1) problems with the service application process (N = 296); (2) critiques of the services offered (N = 270) including either problems with community care support services or institutional care. 74 indicated that they had no need for services, and 15 praised the services they had received. Conclusions. From the caregiver's perspective, the service system is complicated, bureaucratic and works organization centredly.

[Update on current care guidelines. The diagnosis and medical treatment of memory disorders]. / Muistisairauksien diagnostiikka ja lääkehoito.

Any complaints from a patient about their memory should be examined. Diagnosis is based on international criteria. The basic evaluation consists of the medical history, clinical evaluation, cognitive tests and brain imaging, especially using MRI. When a diagnosis of Alzheimer's disease, AD with cerebrovascular disease or with Lewy Body disease, or Dementia associated with Parkinson's disease or LBD is made, evidence based medical therapy is indicated as part of comprehensive care. An acetylcholinesterase inhibitor or memantine can be used. These drugs are ineffective in the case of frontotemporal degenerations. For severe behavioural disorders, other psychoactive medications can be applied.

Exercise rehabilitation on home-dwelling patients with Alzheimer's disease--a randomized, controlled trial. Study protocol.

BACKGROUND: Besides cognitive decline, Alzheimer's disease (AD) leads to physical disability, need for help and permanent institutional care. The trials investigating effects of exercise rehabilitation on physical functioning of home-dwelling older dementia patients are still scarce. The aim of this study is to investigate the effectiveness of intensive exercise rehabilitation lasting for one year on mobility and physical functioning of home-dwelling patients with AD. METHODS: During years 2008-2010, patients with AD (n = 210) living with their spousal caregiver in community are recruited using central AD registers in Finland, and they are offered exercise rehabilitation lasting for one year. The patients are randomized into three arms: 1) tailored home-based exercise twice weekly 2) group-based exercise twice weekly in rehabilitation center 3) control group with usual care and information of exercise and nutrition. Main outcome measures will be Guralnik's mobility and balance tests and FIM-test to assess physical functioning. Secondary measures will be cognition, neuropsychiatric symptoms according to the Neuropsychiatric Inventory, caregivers' burden, depression and health-related quality of life (RAND-36). Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two year follow-up. DISCUSSION: To our knowledge this is the first large scale trial exploring whether home-dwelling patients with AD will benefit from intense and long-lasting exercise rehabilitation in respect to their mobility and physical functioning. It will also provide data on cost-effectiveness of the intervention. TRIAL REGISTRATION: ACTRN12608000037303.

Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the SERAD study): a randomised, placebo-controlled, double-blind trial.

BACKGROUND: The efficacy of galantamine has been shown in patients with mild, moderate, and advanced moderate Alzheimer's disease (AD). Here we report its efficacy in patients with severe AD. METHODS: Between December, 2003, and March, 2007, patients aged 84 (SD 6) years with severe AD (mini-mental state examination [MMSE] score 5-12 points), in a nursing home setting were randomly assigned to receive galantamine (n=207), titrated initially to 24 mg/day, or placebo (n=200). Co-primary efficacy measures for cognitive function and ability to undertake normal daily activities were the severe impairment battery (SIB) and the seven-item minimum data set-activities of daily living (MDS-ADL), respectively. Adverse events, vital signs, laboratory parameters, and electrocardiograms were monitored. This trial is registered with ClinicalTrials.gov, number NCT00216593. FINDINGS: 168 of 207 (81%) patients in the galantamine group and 161 of 200 (81%) in the placebo group completed the study. Mean SIB scores increased (improved) by 1.9 (95% CI -0.1 to 3.9) points with galantamine and decreased (worsened) by 3.0 (-5.6 to -0.5) points with placebo (between-group least squares mean difference 4.36, 1.3 to 7.5; p=0.006). Mean MDS-ADL self-performance score worsened by 1.2 (0.6 to 1.8) points and 1.6 (0.8 to 2.3) points, respectively (between-group least squares mean difference -0.41, -1.3 to 0.5; p=0.383). Nominally significant between-group differences in favour of galantamine occurred for the SIB domains of memory (p=0.006), praxis (p=0.010), and visuospatial ability (p=0.002), and for the MDS-ADL subitem locomotion on unit (p=0.021). 183 of 207 patients (88%) who received galantamine and 177 of 200 (89%) who received placebo had adverse events, which were mostly mild to moderate. Eight patients (4%) in the galantamine group and 21 patients (11%) in the placebo group died. ECG abnormalities were similar between the two groups. INTERPRETATION: Galantamine can be started and used safely in elderly patients with severe AD. Galantamine improved cognitive function but failed to significantly improve the co-primary parameter of overall activities of daily living.

How do officially organized services meet the needs of elderly caregivers and their spouses with Alzheimer's disease?

The caregiving situation among caregivers and their spouses with Alzheimer's disease, the support and services received, the unmet needs, and the caregivers' satisfaction with the services are examined. The study included a survey of a random sample of 1943 caregivers of persons with Alzheimer's disease in Finland. Mean age of the caregivers was 78.2 years, and 35% had poor subjective health. Disabilities and behavioral symptoms were common among the spouses with Alzheimer's disease. The services most often offered were financial support (36%), technical devices (33%), physiotherapy (32%), and respite care in nursing homes (31%). Most often needed services were physiotherapy for the spouse with dementia (56%), financial support (50%), house-cleaning (41%), and home respite (40%). Only 39% of the caregivers were satisfied with the services, and 69% felt they did not have any influence on what services were offered. It was concluded that official services poorly meet the needs of these caregivers.

Neither atypical nor conventional antipsychotics increase mortality or hospital admissions among elderly patients with dementia: a two-year prospective study.

BACKGROUND: Antipsychotics are widely used to manage behavioral disorders in patients with dementia. Recently, serious concerns have been raised about the stroke and mortality risk of atypical antipsychotics when administered to patients with dementia. AIM: The aim of this study was to examine the impact of atypical and conventional antipsychotics on mortality and hospital admissions among Finnish elderly institutionalized patients with dementia in a two-year follow up and to compare their prognosis with that of nonusers. PATIENTS AND METHODS: The authors examined 254 very frail patients with dementia, mean age 86 years, from seven Finnish nursing homes and two hospitals in 1999-2000. Medical records provided information on the use of daily antipsychotic medication; central registers confirmed mortality for up to two years. RESULTS: Nearly one-half (48.4%) of the patients used antipsychotic medication: 37.4% received conventional neuroleptics (N = 95) and 11.0% received atypical antipsychotics (N = 28). The mean number of hospital admissions was higher among the nonusers than among the users of conventional or atypical antipsychotics. Of the users of atypical antipsychotics (risperidone, olanzapine), 32.1% died within 2 years. The respective figures for users of conventional neuroleptics were 45.3%, and for the nonusers, 49.6%. In the Cox proportional hazard model, a high number of medications and the use of physical restraint predicted higher mortality at two years. The use of atypical antipsychotics showed lower risk of mortality, if any. The respective test for conventional antipsychotics was nonsignificant. CONCLUSION: Among these frail and very old patients with dementia, neither the use of atypical antipsychotics nor the use of conventional neuroleptics increased mortality or hospital admissions. The use of restraints, however, doubled the risk of mortality.

Use of inappropriate medications and their prognostic significance among in-hospital and nursing home patients with and without dementia in Finland.

BACKGROUND: Although the Beers criteria have been frequently utilised to describe the use of inappropriate medications in various elderly populations, less is known about the use of such medications among patients with dementia, and nor have many studies dealt with their impact on mortality or use of healthcare services. This study examines the use of inappropriate drugs and their impact on mortality and use of health services among Finnish elderly nursing home and hospital patients. Patients with dementia were studied as a special subgroup. METHODS: A total of 425 patients consecutively admitted to seven Finnish nursing homes and two hospitals in 1999-2000 were examined. Details of all medications prescribed and administered were retrieved from medical records and coded according to the Beers 1997 criteria. Mortality data as well as days in acute hospital were obtained from central registers and all area hospitals during 2 years of follow-up. RESULTS: The entire population was old and frail (mean age 86 years, 82% females), 60% had dementia and 36.2% received at least one potentially inappropriate drug (PID). No differences existed in the proportion of users of PIDs among those 60% of patients with dementia compared with those without. The most common PID was temazepam, with 14% of all patients on high doses. Other commonly used PIDs were oxybutynin and dipyridamole. Amitriptyline was more commonly used among patients without dementia (4.7%) compared with those with dementia (0.8%). Nevertheless, in this very old and frail study population, use of inappropriate drugs did not predict mortality or use of health services. CONCLUSION: Use of PIDs is common in nursing homes and hospitals in Finland but has no impact on mortality or hospital admissions. Use of high-dose temazepam as a hypnotic accounted for most of the high use of PIDs.