Awareness of disease in Alzheimer's dementia: description of a mild to moderate sample of patient and caregiver dyads in Brazil

BACKGROUND: Impairment of deficit awareness is a clinically relevant feature of dementia affecting the maintenance of decision capacities, management and safety of patients with risk behaviors, and caregiver burden. This study assessed awareness of disease of patient/caregiver dyads and the relationship between unawareness on various domains and sociodemographic variables among elderly Brazilians with Alzheimer's disease (AD). METHODS: The dyads (n=52), stratified by clinical severity and age groups, responded to the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia (ASPIDD). Statistical tests were used to compare clinical and sociodemographic variables and to calculate differences in rates of discrepant responses among mild and moderate dyads and between age groups, rates of discrepant responses among the ASPIDD domains, and association between awareness and age/age at onset. RESULTS: Awareness of deficits did not differ significantly among mild patients, whereas moderate patients showed impaired recognition on all domains. Older moderate dyads showed more discrepant responses, as compared to younger dyads at both severity stages. Mild patients could associate the disease with the cognitive deficits and recognized impairments on other domains. There was no significant relation of awareness with age at onset. CONCLUSION: Mild AD patients could associate the disease process with the presence of cognitive deficits, and also the changes in the emotional response with difficulties in social, family, and affective relations. Moderate AD patients were less aware of the symptoms and did not attribute them to the disease.     

Apraxic disturbances in patients with mild to moderate Alzheimer's disease

Twenty-two patients meeting the NINCDS–ADRDA diagnostic criteria for probable AD were included in the study, along with 10 matched controls. Praxic disturbances were investigated using eight tasks and the results were interpreted according to the neuropsychological model of Roy and Square modified by Rothi et al. (1988) [Aphasiology 21:381–388] which distinguishes a conceptual system concerned with knowledge of the action and function of gestures and a production system that effects gestures in the environment. Disturbance of the production system was found only in 17 patients. Disturbance of the production system was correlated to disturbance of verbal comprehension. The patients scored lower using the left hand than the right. Disturbance of the conceptual system was found in all patients and was not significantly correlated with other cognitive deficits. No significant difference in results was found according to the type of input to the conceptual system (visual or verbal). Deficits in tasks using real objects were correlated to disturbances of both the production and conceptual systems. Most patients performed poorly both in tasks exploring the conceptual system and in those exploring the production system. However, two patients performed badly in production tasks but had performances in the range of controls for conceptual tasks and one patient had the opposite pattern of dissociation. This provides evidence that the production and the conceptual system are independent. Impairment in the ability to perform everyday activities was correlated to disturbances of the conceptual system whereas poor performances in tasks exploring the production system or in using real objects were not.     

Measuring awareness in people with mild to moderate Alzheimer's disease: development of the Memory Awareness Rating Scale--adjusted

Variations in level of awareness among people with Alzheimer's disease (AD) may impact on well-being for the person with dementia and their carer, and may influence outcomes of cognitive rehabilitation interventions. Awareness has often been assessed using discrepancies between self and proxy rating or between self-rating and objective task performance, with the latter considered to be preferable. Measures are available that are suitable for people with mild AD, for example the Memory Awareness Rating Scale (MARS). However, these may be less appropriate for people whose impairments are more advanced and who consequently have more difficulty with the objective task component. In order to provide a measure suitable for people with moderate AD, an adjusted Memory Awareness Rating Scale (MARSA) was developed by altering the objective task component of the MARS. The MARSA was piloted with 41 participants with mild to moderate AD. It was found to be suitable for use with a broader group of participants than the MARS. The component ratings were found to have good internal consistency. The component ratings and the two indices of awareness had high test-retest reliability. The extension of the original measure offers the opportunity to consider awareness throughout the course of the disease and provides a basis for longitudinal investigations of awareness.     

Olanzapine does not enhance cognition in non-agitated and non-psychotic patients with mild to moderate Alzheimer's dementia

OBJECTIVE: This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms. METHODS: Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy. RESULTS: Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p = 0.03) and 26 (p = 0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14-18) (n = 35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n = 24; p < 0.001); whereas in patients with less cognitive impairment (n = 78, baseline MMSE scores of 23-26) between-group ADAS-Cog changes were not significant. CONCLUSIONS: In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.     

Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results

BACKGROUND: Laboratory evidence of cholesterol-induced production of amyloid beta as a putative neurotoxin precipitating Alzheimer disease, along with epidemiological evidence, suggests that cholesterol-lowering statin drugs may favorably influence the progression of the disorder. OBJECTIVE: To determine if treatment with atorvastatin calcium affects the cognitive and/or behavioral decline in patients with mild to moderate Alzheimer disease. DESIGN: Pilot intention-to-treat, proof-of-concept, double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40-mg tablets) or placebo using last observation carried forward analysis of covariance as the primary method of statistical assessment. PARTICIPANTS: Individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination score of 12-28) were recruited. Of the 98 participants providing informed consent, 71 were eligible for randomization, 67 were randomized, and 63 subjects completed the 3-month visit and were considered evaluable. MAIN OUTCOME MEASURES: The primary outcome measures were change in Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Global Impression of Change Scale scores. The secondary outcome measures included scores on the Mini-Mental State Examination, Geriatric Depression Scale, the Neuropsychiatric Inventory Scale, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. The tertiary outcome measures included total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels. RESULTS: Atorvastatin reduced circulating cholesterol levels and produced a positive signal on each of the clinical outcome measures compared with placebo. This beneficial effect reached significance for the Geriatric Depression Scale and the Alzheimer's Disease Assessment Scale-cognitive subscale at 6 months and was significant at the level of a trend for the Alzheimer's Disease Assessment Scale-cognitive subscale, Clinical Global Impression of Change Scale, and Neuropsychiatric Inventory Scale at 12 months assessed by analysis of covariance with last observation carried forward. CONCLUSION: Atorvastatin treatment may be of some clinical benefit and could be established as an effective therapy for Alzheimer disease if the current findings are substantiated by a much larger multicenter trial.     

Utility of the Bender Gestalt Test for differentiation of dementia with Lewy bodies from Alzheimer's disease in patients showing mild to moderate dementia

AIMS: We examined the utility of the Bender Gestalt Test (BGT) for the differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD), comparing BGT scores between DLB and AD patients showing mild to moderate dementia. METHODS: Eighteen DLB patients, 36 AD patients controlled by age, years of education, Clinical Dementia Rating and Mini Mental State Examination scores, and 21 nondemented elderly participants controlled by age and years of education were subjected to the BGT. Their BGT performances were scored according to the Pascal-Suttell method. RESULTS: The DLB group showed significantly higher (that is worse) BGT scores than the other groups. When a cutoff point of 98 was used to differentiate DLB from AD, the patients exceeding 98 were 94% in the DLB group, 17% in the AD group and 0% in the control group. The sensitivity and specificity of this cutoff point were 0.94 and 0.89, respectively. CONCLUSION: The BGT is a useful neuropsychological test to differentiate DLB from AD.     

Rivastigmine in current clinical practice in patients with mild to moderate Alzheimer's disease

Six hundred and sixty nine out patients with mild to moderate Alzheimer's disease were enrolled by 193 French neurologists, psychiatrists and gerontologists. The patients, 38p.cent males and 62p.cent females with a mean age of 75 years were progressively titrated from 3 to 12mg by day of rivastigmine, Exelon((R)), a day, and treated for 6 months. Mean Mini-Mental State (MMS) at baseline was 18.6. Concomitant pathologies and treatments were present in 89p.cent of the patients. Safety was good though 86p.cent reported an adverse event which was mild in most of the cases. The premature drop out rate was 29p.cent. Seventy-five patients showed no change or an improvement in their 4 Instrumental Activities of Daily Living (IADL) score with no change in the MMS at the end of treatment (18.8). Four items of the Neuro-Psychiatric Inventory (NPI): delusions, anxiety, apathy, and irritability were significantly improved at week 12 and the improvement in anxiety was still significant at the end of treatment. The total score frequency X severity showed a tendency to improvement. The correlations between the sum of the 4 IADL, MMS and NPI scores were strongly significant.     

Semantic organization and verbal episodic memory in patients with mild and moderate Alzheimer's disease

The objective of the present research was to investigate the relationship between semantic organization and cue utilization in mildly and moderately demented patients with Alzheimer's disease (AD). In Experiment 1, subjects were presented with two lists of words: a list with semantically unrelated words and a list with words from four semantic categories presented randomly intermixed. Free recall was assessed and following the organizable list, subjects received a cued recall test. Normal controls, as opposed to mildly and moderately demented patients, showed higher performance in the organizable list as compared to the random list. In addition, normal controls and mildly demented patients benefited from semantic cues in the organizable list and performed at a higher level in total recall as compared to free recall. In Experiment 2, subjects were presented with two lists of words: a list with words from four semantic categories presented randomly intermixed and a list with words from four semantic categories presented clustered, together with information about the organization of the list. Free recall and cued recall, with the category names serving as cues, were assessed. Free recall performance of normal controls was higher in the clustered than in the organizable list, whereas no such effect was observed for the AD patients. Normal controls and mildly demented patients performed at a higher level in total as compared to free recall in both lists, whereas this effect was present only in the clustered list for the moderately demented patients. The overall pattern of results indicates that there are conditions under which memory facilitation from semantic organization may be obtained in AD.     

Sleep disturbance in mild to moderate Alzheimer's disease

BACKGROUND AND PURPOSE: To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates. PATIENTS AND METHODS: Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis. RESULTS: The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD 'aggressiveness' (P=0.009) and 'global rating' (P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD. CONCLUSIONS: Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.     

Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer's disease

Donepezil is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). Since behavioral symptoms severely affect quality of life for AD patients and their caregivers, predicting behavioral responses to donepezil will be useful in managing patients with AD. In this study, we analyzed 70 consecutive cases with mild to moderate AD. Caregivers were interviewed with the Neuropsychiatric Inventory for behavioral assessment and 4-point improvement at week 12 was accepted as a treatment response. Twenty-one (30.0%) patients showed a behavioral response, while 42 (60.0%) showed no behavioral change and 7 (10.0%) worsened. Dysphoria, anxiety and apathy significantly improved after treatment among the responder group. The baseline profile including age, sex, Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Geriatric Depression Scale did not differ significantly among the three groups. Statistical Parametric Mapping analysis of single photon emission computed tomography (SPECT) images at baseline showed that cerebral blood flow in the premotor and parietotemporal cortices was significantly higher in the responder group than in the worse group. The present study suggested usefulness of SPECT imaging in the prediction of behavioral response to donepezil among AD patients even with similar psychiatric symptoms and cognitive functions.     

Neuropsychiatric symptoms in mild dementia with lewy bodies and Alzheimer's disease

Background/Aims: To compare neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and dementia with Lewy bodies(DLB). Methods: Neuropsychiatric symptoms and caregiver distress were assessed using the Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and compared across the two groups using non-parametric tests. Results: The DLB patients had a higher NPI totalscore (median 24 vs. 11.5, p < 0.005), more numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2, p < 0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003). Conclusions: In mild dementia, DLB patients have more neuropsychiatric symptoms and more associated caregiver distress compared with AD.     

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study

Memantine is a moderate affinity, uncompetitive NMDA receptor antagonist currently approved for the treatment of moderate to severe Alzheimer's disease (AD). A 24-week, double-blind, placebo-controlled, study (Study 99679) conducted in Europe evaluated the efficacy and tolerability of 20mg/day memantine in patients with mild to moderate AD. Patients were randomised to either memantine or placebo in a 2:1 ratio. Efficacy was primarily assessed as change from baseline in ADAS-cog and CIBIC-plus score. Of 470 patients randomised and treated (memantine, n=318; placebo, n=152), 85% and 91% completed the study. Memantine-treated patients showed statistically significant improvement relative to placebo at weeks 12 and 18, and numerical superiority at week 24 on both efficacy scales. The lack of significance at week 24 was attributed to an unexpectedly high placebo response. Memantine was well tolerated with an adverse event profile similar to placebo. The data presented support the efficacy of memantine in mild to moderate AD.     

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study

Memantine is a moderate affinity, uncompetitive NMDA receptor antagonist currently approved for the treatment of moderate to severe Alzheimer's disease (AD). A 24-week, double-blind, placebo-controlled, study (Study 99679) conducted in Europe evaluated the efficacy and tolerability of 20 mg/day memantine in patients with mild to moderate AD. Patients were randomised to either memantine or placebo in a 2:1 ratio. Efficacy was primarily assessed as change from baseline in ADAS-cog and CIBIC-plus score. Of 470 patients randomised and treated (memantine, n=318; placebo, n=152), 85% and 91% completed the study. Memantine-treated patients showed statistically significant improvement relative to placebo at weeks 12 and 18, and numerical superiority at week 24 on both efficacy scales. The lack of significance at week 24 was attributed to an unexpectedly high placebo response. Memantine was well tolerated with an adverse event profile similar to placebo. The data presented support the efficacy of memantine in mild to moderate AD.