Asmus Vogel

Awareness of Deficits in Mild Cognitive Impairment and Alzheimer’s Disease: Do MCI Patients Have Impaired Insight?

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective research program 36 consecutive patients with mild AD (MMSE above 19), 30 with amnesic MCI and 33 matched controls were examined. Using three methods for awareness assessment we found no significant differences in the level of awareness between MCI and AD. Both groups had impaired awareness and significant heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected dementia disorders.

Semantic Memory Impairment in the Earliest Phases of Alzheimer’s Disease

The presence and the nature of semantic memory dysfunction in Alzheimer’s disease (AD) have been widely debated. This study aimed to determine the frequency of impaired semantic test performances in mild AD and to study whether incipient semantic impairments could be identified in predementia AD. Five short neuropsychological tests sensitive to semantic memory and easily applicable in routine practice were administered to 102 patients with mild AD (Mini-Mental State Examination score above 19), 22 predementia AD patients and 58 healthy subjects. ‘Category fluency’ and ‘naming of famous faces’ were the most frequently impaired tests in both patient groups. The study demonstrated that impairments on semantically related tests are common in mild AD and may exist prior to the clinical diagnosis. The results imply that assessment of semantic memory is relevant in the evaluation of patients with suspected AD.

Efficacy of psychosocial intervention in patients with mild Alzheimer’s disease: the multicentre, rater blinded, randomised Danish Alzheimer Intervention Study (DAISY)

Objective To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer’s disease and their primary care givers. Design Multicentre, randomised, controlled, rater blinded trial. Setting Primary care and memory clinics in five Danish districts. Participants 330 outpatients with mild Alzheimer’s disease and their 330 primary care givers. Interventions Participating dyads (patient and primary care giver) were randomised to control support during follow-up or to control support plus DAISY intervention (multifaceted and semi-tailored counselling, education, and support). Main outcome measures Primary outcomes at 12 months for patients were change from baseline in mini mental state examination (MMSE) score, Cornell depression scale score, and proxy rated European quality of life visual analogue scale (EQ-VAS) score. For care givers, outcomes were change from baseline in geriatric depression scale (GDS 30 items) score and EQ-VAS score. Results Because of multiple testing, statistical significance was set at an adjusted P limit of <0.0005. At 12 months there were no significant differences between the two allocation groups in changes from baseline in the primary and secondary outcomes. However, although non-significant with the adjusted P limit, a small difference was observed for one of the primary patient outcomes (Cornell depression scale score) in patients in favour of the DAISY intervention group before and after adjusting for attrition (P=0.0146 and P=0.0103 respectively). Conclusions The multifaceted, semi-tailored intervention with counselling, education, and support for patients with mild Alzheimer’s disease and their care givers did not have any significant effect beyond that with well structured follow-up support at 12 months after adjustment for multiple comparisons. The small positive effect found in the unadjusted primary outcome addressing depressive symptoms in patients may call for further research focusing on patients with Alzheimer’s disease and comorbid depression. Trial registration ISRCTN74848736.

Heterogeneity in executive impairment in patients with very mild Alzheimer's disease.

Background/Aims: The presence of executive impairment in mild Alzheimer’s disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe the frequency of impairment on a set of internationally well-known executive tests in patients with very mild AD. Methods: Thirty-six patients with very mild AD (MMSE scores above 23) and 32 healthy control subjects were administered a battery of 7 executive tests: Trail Making part B, Stroop Interference Test, modified Wisconsin Card Sorting Test (WCST), category- and letter-based verbal fluency, a design fluency task and the Similarities subtest from WAIS. Impairment was defined as a score of 2 SD or more below control means. Results: Executive impairment on at least 1 measure was seen in 76% of the patients, and 50% were impaired on 2 or more tests. Trail Making B and Stroop Interference Test were impaired in more than 40%, whereas only few patients were impaired on Similarities, WCST and design fluency. A wide variation of executive test profiles was seen among the patients. Conclusion: Executive impairments are common in early AD and not just a feature characteristic of a subgroup of patients. Complex attentional skills are more frequently affected than other executive functions. There is, however, considerable heterogeneity among AD patients in the pattern of executive dysfunction.

The Executive Interview as a Screening Test for Executive Dysfunction in Patients with Mild Dementia

Objectives: To validate the Executive Interview (EXIT25) as a screening instrument for executive cognitive dysfunction in patients with mild dementia.

Validation of the Danish Addenbrooke's Cognitive Examination as a Screening Test in a Memory Clinic

Background: Addenbrooke’s Cognitive Examination (ACE) is a cognitive screening test developed to detect dementia. It has been validated in several countries. Validation studies have predominantly included patients with various degrees of dementia and healthy controls. Objective: The aim of this study was to evaluate the Danish version of ACE as a screening test for early dementia in an outpatient memory clinic. Further, we wanted to investigate the ability of the ACE to discriminate patients with early Alzheimer’s disease (AD) from patients with depression. Method: 78 patients with mild AD (MMSE ≥20), 30 non-demented patients diagnosed with depression (originally referred for evaluation of cognitive symptoms), and 63 healthy volunteers, all between 60 and 85 years of age, were included. All patients were given the ACE as a supplement to the standard diagnostic work-up. Results: The cut-off points for optimal trade-off between sensitivity and specificity for ACE were 85/86 (sensitivity 0.99, specificity 0.94). When these cut-off points were applied to the group of depressive patients, the specificity dropped to 0.64, indicating a great overlap in individual test scores for demented and depressed patients. Conclusion: The optimal cut-off points for ACE found in this Danish study were close to what is reported in most other European studies. The great overlap in ACE scores for demented and depressed patients emphasize that test scores must be interpreted with great caution when used in diagnostic work-up.

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial

BACKGROUND Studies of physical exercise in patients with Alzheimers disease (AD) are few and results have been inconsistent. OBJECTIVE To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. METHODS In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. RESULTS The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. CONCLUSIONS This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

A three-year follow-up on the efficacy of psychosocial interventions for patients with mild dementia and their caregivers: the multicentre, rater-blinded, randomised Danish Alzheimer Intervention Study (DAISY)

Objectives To examine the long-term efficacy at the 36-month follow-up of an early psychosocial counselling and support programme lasting 8–12 months for community-dwelling patients with mild Alzheimers disease and their caregivers. Design Multicentre, randomised, controlled, rater-blinded trial. Setting Primary care and memory clinics in five Danish districts. Participants 330 home-dwelling patients with mild Alzheimers disease and their primary caregivers (dyads). Interventions Dyads were randomised to receive intervention during the first year after diagnosis. Both intervention and control groups had follow-up visits at 3, 6, 12 and 36 months. Main outcome measures Primary outcomes for the patients assessed at 36-month follow-up were changes from baseline in global cognitive function (Mini-Mental State Examination), depressive symptoms (Cornell Depression Scale) and proxy-rated EuroQoL quality of life on visual analogue scale. The primary outcomes for the caregivers were changes from baseline in depressive symptoms (Geriatric Depression Scale) and self-rated EuroQoL quality of life on a visual analogue scale. The secondary outcome measures for the patient were proxy-rated Quality of Life Scale for Alzheimers disease (QoL-AD), Neuropsychiatric Inventory-Questionnaire, Alzheimers disease Cooperative Study Activities of Daily Living Scale, all-cause mortality and nursing home placement. Results At a 36-month follow-up, 2 years after the completion of the Danish Alzheimer Intervention Study (DAISY), the unadjusted positive effects previously detected at the 12-month follow-up in one patient primary outcome (Cornell depression score) and one patient secondary outcome (proxy-rated QoL-AD) disappeared (Cornell depression score, p=0.93; proxy-rated QoL-AD, p=0.81). No long-term effect of DAISY intervention on any other primary and secondary outcomes was found at the 36-month follow-up. Conclusions For patients with very mild Alzheimers disease and their caregivers, an intensive, multi-component, semitailored psychosocial intervention programme with counselling, education and support during the first year after diagnosis did not show any positive long-term effect on primary and secondary outcomes. Trial registration The study was registered in the Clinical Trial Database (http://www.controlled-trials.com/ISRCTN74848736).

Assessment of dementia in ethnic minority patients in Europe: a European Alzheimer's Disease Consortium survey

BACKGROUND In most European countries the ethnic minority migrant populations are currently reaching an age where dementia becomes an increasingly important issue. There is no European consensus on good clinical practice with these patient groups, who often have special needs and expectations with regard to dementia services. METHODS A survey was conducted in clinical dementia centers in 15 European countries. Questionnaires focusing on different points in the clinical assessment of dementia in ethnic minority patients were mailed to leading dementia experts of the European Alzheimers Disease Consortium. RESULTS Thirty-six centers from 15 countries responded to the survey. Ethnic minority patients were seen on a regular basis in 69% of these centers. The diagnostic evaluation was in accordance with evidence-based clinical guidelines in 84-100% of the centers, but most centers performed cognitive assessment with instruments that are only validated in Western cultures and frequently relied on family members for interpretation. Diagnostic evaluation of the patients was considered to be challenging in 64% of the centers, mainly because of communication problems and lack of adequate assessment tools. In general, there were few indicators of culturally sensitive dementia services in the centers. CONCLUSIONS Ethnic minority patients are seen on a regular basis in European dementia clinics. Assessment of such patients is difficult for a number of reasons. Results from this study show that the most challenging issues are communication problems and assessment of cognitive function where there is a need to develop specific tests for ethnic minority patients.

Generic and Disease-Specific Measures of Quality of Life in Patients with Mild Alzheimer’s Disease

Background/Aim: The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer’s disease (AD). Methods: The participants were 321 home-living patients with mild AD and their primary caregivers from the Danish Alzheimer Intervention Study. QoL was assessed using the generic EuroQol-5D with visual analogue scale (VAS) and the disease-specific Quality of Life in Alzheimer’s Disease (QOL-AD) scales (both caregiver and patient rated). Depression, activities of daily living, cognitive performance and neuropsychiatric symptom severity were also assessed. Results: All 3 caregiver-rated QoL scales correlated significantly with each other (p < 0.001) and with clinical measures. Patient-rated QoL versions correlated inversely with depression (p < 0.001) but not significantly with any other clinical variables. Conclusion: The caregiver-rated QoL scales showed stronger interscale correlation as well as a similar correlation pattern with standard clinical outcome variables compared to the patient-rated versions. There is some indication that the EQ-5D + VAS could be a suitable alternative to the QOL-AD scale in specific research designs.