Moderate Dementia Of Alzheimer Type Research Articles

Life-space mobility in older adults with Alzheimer's-type dementia

BackgroundMobility is an important component of functioning. Motor and cognitive impairment in older people with Alzheimer's disease can exert a negative impact on life-space mobility. ObjectiveTo compare life-space mobility in older adults with mild and moderate Alzheimer-type dementia and those without dementia and determine associations with health factors. MethodsLife-space mobility was assessed using the Life Space Assessment (LSA) in 33 older adults with Alzheimer-type dementia (AD group) and 24 older adults without dementia (WD group). The World Health Organization Disability Assessment Schedule (WHODAS 2.0), Addenbrooke's Cognitive Examination (ACE-R), Geriatric Depression Scale (GDS), Modified Baecke Questionnaire for Older Adults (MBQOA), and Short Physical Performance Battery (SPPB) were completed. Statistical analysis was performed with unpaired t-test or Mann-Whitney tests for comparisons between groups and Spearman's correlation test. ResultsThe AD group had a lower total LSA score compared to the WD group (44 vs 65, mean difference = −20.7 [95% CI: −28.6, −12.9]), 21% of the AD group were restricted to their homes when no assistance was available. In both groups, moderate correlations were found between LSA and both functioning and physical activity level. Symptoms of depression presented moderate correlation only in the WD group. ConclusionsOlder adults with AD have lower life-space mobility and require assistance to achieve higher levels of mobility. Clinical implications: LSA can help assess life-space mobility. Encouraging and enabling assistance is fundamental to a greater life-space for older adults with dementia

P2‐459: EXECUTIVE CONTROL DEFICITS AS AN EARLY DIAGNOSTIC TO DEMENTIA OF ALZHEIMER'S TYPE

Dementia of Alzheimer's type (DAT) is marked by executive control deficit which allows monitoring and resolution of conflict between different stimuli and responses. The possible underlying cause of executive control deficit may be the dysfunction of inhibitory mechanisms due to the reduced availability of attentional resources early in the course of the disease. Literature have evidenced of deficit in executive control as an early diagnosis to DAT before memory impairment which indicate that as the disease progresses early onset of executive deficit may lead to conversion of patient with amnestic mild cognitive impairment (aMCI) to DAT. The early diagnosis of DAT may reduce its devastating effects. The current research converging on executive control function as an earlier indicator of DAT in patients with mild cognitive impairment (MCI) at preclinical stage. The present study examined the executive control in attentional function among people with aMCI, mild and moderate levels of DAT compared with age-matched healthy controls (HC) by using the attentional network paradigm. The flanker paradigm of Attentional Network Task (ANT) was used to assess executive control effect. The reaction time and performance accuracy of the participants were recorded. The result showed that the inhibitory control function was less efficient in DAT as compared to HC. The aMCI group differed to mild and moderate DAT in response time measure. Further, the post-hoc analysis showed significantly slower performance of aMCI and mild DAT with HC group, the performance of patients with mild DAT was also significantly faster than moderate DAT, however, it was seen that aMCI group showed a non-significant difference with mild DAT group on executive control performance. This non-significant result suggests that the few patients with aMCI who performed significantly different at congruent and incongruent condition may progresses to DAT in comparison to those who don't face difficulty in resolving conflict among responses. The impairment in executive control network in aMCI revealed by difference in performance of response inhibition task could be proven as an early diagnostic to DAT which could further delay the onset of symptoms.

Bright light therapy for sleep disturbance in dementia is most effective for mild to moderate Alzheimer's type dementia: a case series.

Sleep problems in people with dementia are common and place a high burden on caregivers. Although hypnotic agents are often used to treat sleep disturbances, their use is associated with a considerable number of high-risk side-effects such as daytime sleepiness, amnesia, and an increased frequency of falling. The administration of bright light therapy (BLT) in the morning was a non-pharmacological remedy that was expected to treat sleep disorders in patients with dementia by entraining the circadian rhythm to ameliorate disturbances to the normal sleep-wake cycle. However, there are some unsolved issues related to the application of BLT, including the types of dementia for which it is effective and its efficacy in the different stages of cognitive decline and dementia. Furthermore, a protocol for effective BLT has not yet been proposed. In this study, we explored the efficacy of BLT in the treatment of 17 participants, including those with Alzheimer's type dementia (AD) (n = 8), vascular dementia (n = 4), and dementia with Lewy bodies (n = 5). Patients sat in front of the light box for 1 h/day from 0900 to 1000. The patients underwent treatment every day for 2 weeks. BLT led to the improvement of sleep disturbance in four participants, all of whom were AD patients. The four AD patients showed a shorter duration of illness and/or had mild to moderate AD. BLT could be an effective strategy for treating dementia patients, depending on their type and grade of their dementia. To confirm this hypothesis, it would be necessary to study a larger number of cases. Non-pharmacological therapies for sleep disorders should be emphasized as a safe form of treatment for patients with dementia.

Effect of Donepezil on Sleep and Activity in Alzheimer’s Disease: Actigraphic and Polysomnographic Assessment

Aim: To examine the effect of donepezil on sleep and daily activity in patients with Alzheimer-type dementia (ATD) using polysomnography and actigraphy. Methods: Ten patients with mild to moderate ATD (mean age: 76 ± 6.2 years) were studied. The Alzheimer’s disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog),polysomnography, and 7-day recording of actigraphy data were performed. Following this baseline assessment, donepezil (5 mg daily) was administered every morning for 6 weeks, after which the ADAS-Jcog, polysomnography, and actigraphy were repeated. Results: After 6 weeks of treatment with donepezil, daily activity was significantly increased (276.2 ± 89.2 vs. 326.1 ± 98.6; p < 0.05). Similarly, rapid eye movement (REM) sleep (11.3 ± 4.1 vs. 17.1 ± 4.4; p<0.01) and sleep efficiency (76.2 ± 16.3 vs. 82.8 ± 10.6; p<0.05) were significantly increased compared with baseline. Although the ADAS-Jcog score did not decrease significantly (18.5 ± 6.8 vs. 15.9 ± 7.3; P= 0.054), there was a significant positive correlation between the decrease of this score and the increase of daily activity (r= 0.2137, p= 0.4809). Conclusions: An increase of daily activity and cognition were induced by donepezil treatment in patients with ATD, possibly based on improvement of the sleep structure. Trial Registration: Controlled-trials. Com Identifier: UMIN000005018

New Prospectives in the Delivery of Galantamine for Elderly Patients Using the IntelliDrug Intraoral Device: In Vivo Animal Studies

The transbuccal delivery of drugs could assist several categories of chronic, especially elderly, patients in adhering to a correct dosage regimen. In particular, patients suffering from dementia have several difficulties in following the prescribed dosage, in addition to problems associated with swallowing tablets. Galantamine is currently used for treating patients with mild to moderate Alzheimer's-type dementia. The transbuccal delivery of this drug could be an interesting non- invasive and safe administration route. Several studies have been performed in vitro and ex vivo within the framework of a European Commission funded Project (IntelliDrug-FP6), aimed at developing a device which would be fitted for controlled delivery of drugs by an electronic and software-driven system. The primary objective of this study was to evaluate the efficacy of a prototype of the IntelliDrug device in vivo on 6 pigs, following a single Galantamine dose to be delivered through the buccal mucosae, as compared to intravenous drug injection. The secondary objectives were: a) to verify Galantamine bioavailability through buccal delivery; b) to evaluate the permeation enhancement effect of iontophoresis; and, finally, c) to assess any histomorphological changes in the buccal mucosae after transbuccal delivery. The results suggested that transbuccal delivery has the potential to cause long-lasting and controlled blood levels of Galantamine. The latter crosses the entire buccal mucosae, reaching systemic circulation after about 30 minutes and its plasmatic peak approximately 120 minutes after administration. The histological analysis of the buccal mucosae did not reveal any evidence of flogosis or tissue injury. Our results have clearly confirmed that the buccal delivery of Galantamine is a reliable tool with which to overcome the drawbacks associated with the conventional administration route. In general, transbuccal drug delivery has been shown to be an interesting, non-invasive and safe administration route for delivering systemically-acting drugs.

Beta-Amyloid Findings Could Be Alzheimer's Marker

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessBeta-Amyloid Findings Could Be Alzheimer's MarkerAaron LevinAaron LevinSearch for more papers by this authorPublished Online:3 Feb 2006https://doi.org/10.1176/pn.41.3.0020The Holy Grail for researchers studying Alzheimer's disease is an imaging system or biomarker to help diagnose the illness or at least document its progress.A new study from researchers at Washington University in St. Louis takes a step in that direction by combining PET scan imaging and cerebrospinal fluid (CSF) analysis. The process compared the extent of beta-amyloid plaques in the brain with levels of related protein fragments in CSF or blood plasma.Using PET technology, researchers led by Anne Fagan, Ph.D., a research associate professor of neurology at the Washington University School of Medicine, scanned the brains of 24 people aged 48 to 83 to find concentrations of plaques containing beta-amyloid. They used an amyloid-binding agent, Pittsburgh Compound B (PIB), provided by investigators at the University of Pittsburgh. Some participants were cognitively normal while others had very mild, mild, or moderate dementia.Fagan and her colleagues from the Washington University Alzheimer's Disease Research Center also tested CSF and blood plasma for several proteins using enzyme-linked immunosorbent assays.They found no relation between PIB binding and the proteins amyloid-40, tau, phosphor-tau181 in CSF, and amyloid-40 and amyloid-42 in plasma. However, they did observe an inverse relationship between amyloid-42 in CSF and PIB binding at beta-amyloid plaques in the brain.“Subjects fell into two nonoverlapping groups: those with positive PIB binding had the lowest CSF amyloid-42 level, and those with negative PIB binding had the highest level,” wrote the researchers in an online publication of their paper in the Annals of Neurology.Seven subjects showed positive PIB binding and low CSF amyloid-42 levels. Three of those subjects were diagnosed with mild or moderate Alzheimer's-type dementia, and another with very mild symptoms.However, three participants were cognitively normal but had high PIB binding and low CSF levels of amyloid-42, hinting that they were in such a preclinical state. If these subjects eventually develop dementia, this combined technique may indeed prove useful for identifying cases before they reach clinical status. However, if patients such as these never decline cognitively, it may show that plaque number does not always predict the disease.Prior animal studies have suggested that amyloid plaques in the brain may bind beta-amyloid, reducing the movement of soluble beta-amyloid between the brain and the CSF, possibly accounting for the inverse relationship, said the authors. Heavy deposits of beta-amyloid plaques at autopsy are diagnostic for Alzheimer's disease.“These observations suggest that brain amyloid deposition results in low CSF amyloid-42 and that amyloid imaging and CSF amyloid-42 levels may potentially serve as antecedent biomarkers of preclinical Alzheimer's disease,” Fagan said. “[They] support the hypothesis that amyloid deposition in the brain acts as a `sink,' resulting in a new equilibrium between soluble and deposited amyloid-42 in the central nervous system.”“These measures hold potential for identifying individuals with Alzheimer's disease pathology before cognitive symptoms [appear], improving the accuracy of clinical diagnosis, and facilitating the testing of future therapies,” said Fagan in a prepared statement. “But it is important to recognize that this is still a research study, and the findings must be carefully validated before this approach can be considered for clinical use.”“We presently don't have fully validated imaging or biomarker measures that can help us monitor the development or progression of Alzheimer's in living people,” commented Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch at the National Institute on Aging. “This study represents one step in the progress being made toward identifying clinically useful biological measures for AD.”The study was supported by the National Institute on Aging and the Washington University General Clinical Research Center, which is funded by the National Institutes of Health.An abstract of “Inverse Relation Between in Vivo Amyloid Imaging Load and Cerebrospinal Fluid A42 in Humans” is posted at<www3.interscience.wiley.com/cgi-bin/abstract/112219062/ABSTRACT>.▪ ISSUES NewArchived

Effects of donepezil on Alzheimer's disease: The relationship between cognitive function and rapid eye movement sleep

The aim of this study was to observe the effects of donepezil on both the cognitive function and sleep patterns in patients of Alzheimer's Type Dementia (ATD), especially to determine the relationship between the improvement of cognitive function and the amount of rapid eye movement (REM) sleep. A total of 12 patients (7 females, 5 males; age, 73.0 +/- 6.8) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria of probable AD were studied. These patients presented with mild to moderate dementia, which was confirmed by a Clinical Dementia Rating score of 1 or 2. Following baseline examinations consisting of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog) and polysomnography (PSG), 5 mg of donepezil was administered to the patients at breakfast every day. All patients were reassessed 6 weeks later using the same examinations. With sleep patterns, the percentage of REM sleep to total sleep time increased after the administration of donepezil. In addition, it was also found that sleep efficiency was increased and sleep latency was shortened by this administration. Although the ADAS-Jcog score did not decrease significantly, there was significant positive correlation between the decrease of the ADAS-Jcog score and the increase in the percentage of REM sleep. These results indicate the increase action of REM sleep due to activate central cholinergic systems and the possibility to improve sleep conditions due to one-time administration after breakfast of donepezil in mild to moderate ATD. It is concluded that the increase in REM sleep may reflect the improvement of cognitive function in ATD patients.

Does cognitive dysfunction conform to a distinctive pattern in obstructive sleep apnea syndrome?

Obstructive sleep apnea (OSA) is a recognized cause of cognitive dysfunction. By using a cross-sectional comparative study, we aimed to verify whether neuropsychological performance of untreated OSA patients conforms to a distinctive pattern. Forty-nine newly diagnosed, untreated OSA patients, 27 with multi-infarctual dementia (MID), 31 with mild to moderate dementia of Alzheimer type (DAT) and 63 with severe chronic obstructive pulmonary disease (COPD), all free from major comorbid dementing conditions were chosen for the study. The groups were matched for age and education. We found a bimodal distribution of cognitive performance in OSA group, which was therefore divided into two clusters having better (OSAb, n = 35) and worse (OSAw, n = 14) performance on a battery of 10 cognitive indexes. Cognitive performances of OSAb, OSAw, MID, DAT and COPD were compared by discriminant analysis. OSAb performed better than OSAw in all but one test. Deductive thinking and verbal attainment were more severely impaired in OSAw than in COPD patients. Constructive ability, deductive thinking and both verbal attainment and immediate memory were comparably impaired in OSAw and DAT. The mean neuropsychological scores of OSAw and MID were comparable, but 71% of OSAw patients had a distinctive cognitive profile, i.e. a group specific pattern of cognitive dysfunction, according to discriminant analysis. One of four newly diagnosed OSA patients had a severe and distinctive neuropsychological dysfunction mainly involving inductive and deductive thinking, and constructive ability. Some analogy with cognitive pattern of MID suggests that a mainly subcortical damage underlies this dysfunction.

Effects of individualized memory aids on the conversation of persons with severe dementia: A pilot study

Bourgeois has shown that use of simple memory aids enhances the quality of conversation of persons with moderate Alzheimer-type dementia. We replicated Bourgeois' intervention with five people with severe dementia (Mini-Mental State Examination scores 0-4) and diagnoses of Alzheimer-type or vascular dementia, and evaluated the impact of the aids on the proportion of time participants spent on topic in conversation with carers. For three participants, use of the memory aid did not increase the proportion of time-spent on-topic. The remaining two participants, however, spent approximately twice as much time on-topic when using the aid as when conversing without it. Our results extend Bourgeois' work by showing that memory aids are helpful to some people with severe dementia.

Alzheimer Patients' Ability to Read Words with Irregular Stress

The TIB, an Italian version of the National Adult Reading Test (NART), requires the subject to read out a list of Italian words with a dominant (regular) and a less frequent (irregular) stress pattern. It was given to a group of 45 patients with a diagnosis of dementia of Alzheimer type (DAT) and to a matched control group. Both the NART and the TIB are based on the assumption that the ability to translate orthography into phonology is relatively unimpaired in DAT patients. Despite the different language characteristics on which the two tests are based, the present results largely replicate those found for the NART. Patients with mild and moderate DAT did not perform differently from matched controls on the TIB, while they were impaired on the NART. Patients with severe dementia, however, also failed in the TIB test.

Knowing about people and naming them: can Alzheimer's disease patients do one without the other?

It has recently been suggested that patients with semantic breakdown may show the phenomenon of so-called "naming without semantics". If substantiated, this finding would clearly have a major impact on theories of face and object processing, all of which assume that access to semantic knowledge is a prerequisite for successful naming. In order to investigate this issue, we studied recognition, identification (the ability to provide accurate information), and naming of 50 famous faces by 24 patients with mild to moderate dementia of Alzheimer type (DAT) and 30 age-matched controls. The DAT group was impaired in all three conditions. An analysis of the concordance between identification and naming by each patient, for each stimulus item, established that naming a famous face was possible only with semantic knowledge sufficient to identify the person. Our data support the hypothesis that naming is not possible unless semantic information associated with the target is available. Naming without semantics, therefore, did not occur in patients with DAT. By contrast, there were 206 instances (17% of the total responses) in which the patients were able to provide detailed, accurate identifying information yet were unable to name the person represented. The implication of these findings for models of face identification and naming are discussed.

Correlations of topographical EEG features with clinical severity in mild and moderate dementia of Alzheimer type.

Quantitative electroencephalography (qEEG) and the Folstein Mini Mental State examination (MMSE) were obtained from 31 patients affected by probable dementia of Alzheimer's type (DAT). qEEG data were examined both by spectral analysis (Fast Fourier Transformation) and by single frequency band topographical centroid, and compared with those of 24 healthy subjects of the same age group. DAT patients were found to have higher absolute power in the slow (delta and theta) frequency bands. Quantitative topographical assessment showed significantly more anteriorly located centers of gravity for the alpha and beta activity. Only alpha anteriorization was correlated with the degree of cognitive impairment as measured by the global deterioration scale and MMSE. It is concluded that quantitative topographical assessment was successful for the statistical handling of the EEG power maps, and to identify a potential parameter for the functional staging of the disease.

Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's-type dementia.

Neuropsychological function and resting regional neocortical glucose metabolism, as measured by positron-emission tomography, were studied in 22 patients with mild and moderate Alzheimer's-type dementia. Metabolic reductions in the parietal association cortex and increased left-right metabolic asymmetry were observed in patients with mild and moderate degrees of dementia. Five patients with mild dementia had no impairment of neocortically mediated neuropsychological function, yet they demonstrated these same neocortical metabolic abnormalities. Asymmetry of neocortically mediated, neuropsychological functions correlated with metabolic asymmetries in patients with moderate but not mild dementia. These results suggest that physiological dysfunction in the that physiological dysfunction in the association neocortex is evident in early Alzheimer's-type dementia before the neuropsychological consequences of that dysfunction are demonstrable.

Processes of verbal memory failure in alzheimer-type dementia

Multiple aspects of verbal learning and memory performance in mild as compared to moderate Alzheimer-type dementia (ATD) were studied with the Buschke selective reminding paradigm. Results show that (1) both groups of ATD subjects depend less on long-term memory (LTM) and more on short-term memory (STM) relative to elderly control subjects, (2) mild ATD subjects show less LTM encoding than moderate ATD subjects, (3) moderate ATD subjects retrieve a smaller portion of the items presumed to be encoded into LTM than do mild ATD subjects, and (4) high-imagery words increase LTM encoding and retrieval as compared to low-imagery words for moderate ATD subjects only. These results are explained by the inability of ATD subjects to attend to more than one component of the list-learning task, in conjunction with differences in the deployment of attention between mild and moderate ATD subjects.