Dementia Of The Alzheimer Type Patients Research Articles

A Comparison of Memory Beliefs, Cognitive Activity, and Depression Among Healthy Older Adults, Amnestic Mild Cognitive Impairment, and Patient with Alzheimer's Disease.

BackgroundAmnestic mild cognitive impairment (aMCI) is highly likely to progress to dementia of the Alzheimer type (DAT). One of the most frequently reported symptoms in aMCI and DAT patients is memory impairment. This study compared the levels of beliefs about memory efficacy and control, cognitive activity, and depression among healthy older adults (OA), patients with aMCI, and patients with DAT.MethodsThis study included 21 OA (11 males, 10 females), 16 aMCI patients (6 males, 10 females), and 18 DAT patients (10 males, 8 females). The memory efficacy questionnaire, memory control questionnaire, cognitive activity questionnaire, depression questionnaire, and Seoul Verbal Learning Test were administered to all subjects.ResultsDAT patients showed significantly lower scores on the recognition test than did the OA and aMCI patients, and no difference in these scores was observed between the OA and aMCI patients. Regarding the memory efficacy, memory control, and cognitive activity questionnaires, DAT and aMCI patients showed significantly lower scores than did OA. However, there were no differences in these scores between aMCI and DAT patients.ConclusionThe results of this study suggest that aMCI patients experienced impairment in memory beliefs and memory control in the same way as DAT patients did. These results suggest that the early application of cognitive rehabilitation therapy for patients with aMCI may be effective in preventing or alleviating memory deterioration.

Clinical and multimodal biomarker correlates of ADNI neuropathological findings

BackgroundAutopsy series commonly report a high percentage of coincident pathologies in demented patients, including patients with a clinical diagnosis of dementia of the Alzheimer type (DAT). However many clinical and biomarker studies report cases with a single neurodegenerative disease. We examined multimodal biomarker correlates of the consecutive series of the first 22 Alzheimer’s Disease Neuroimaging Initiative autopsies. Clinical data, neuropsychological measures, cerebrospinal fluid Aβ, total and phosphorylated tau and α-synuclein and MRI and FDG-PET scans.ResultsClinical diagnosis was either probable DAT or Alzheimer’s disease (AD)-type mild cognitive impairment (MCI) at last evaluation prior to death. All patients had a pathological diagnosis of AD, but only four had pure AD. A coincident pathological diagnosis of dementia with Lewy bodies (DLB), medial temporal lobe pathology (TDP-43 proteinopathy, argyrophilic grain disease and hippocampal sclerosis), referred to collectively here as MTL, and vascular pathology were present in 45.5%, 40.0% and 22.7% of these patients, respectively. Hallucinations were a strong predictor of coincident DLB (100% specificity) and a more severe dysexecutive profile was also a useful predictor of coincident DLB (80.0% sensitivity and 83.3% specificity). Occipital FDG-PET hypometabolism accurately classified coincident DLB (80% sensitivity and 100% specificity). Subjects with coincident MTL showed lower hippocampal volume.ConclusionsBiomarkers can be used to independently predict coincident AD and DLB pathology, a common finding in amnestic MCI and DAT patients. Cohorts with comprehensive neuropathological assessments and multimodal biomarkers are needed to characterize independent predictors for the different neuropathological substrates of cognitive impairment.

Verbal and nonverbal memory in primary progressive aphasia: the Three Words-Three Shapes Test.

Objectives: To investigate cognitive components and mechanisms of learning and memory in primary progressive aphasia (PPA) using a simple clinical measure, the Three Words Three Shapes Test (3W3S). Background: PPA patients can complain of memory loss and may perform poorly in standard tests of memory. The extent to which these signs and symptoms reflect dysfunction of the left hemisphere language versus limbic memory network remains unknown. Methods: 3W3S data from 26 patients with a clinical diagnosis of PPA were compared with previously published data from patients with typical dementia of the Alzheimer type (DAT) and cognitively healthy elders. Results: PPA patients showed two bottlenecks in new learning. First, they were impaired in the effortless (but not effortful) on-line encoding of verbal (but not non-verbal) items. Second, they were impaired in the retrieval (but not retention) of verbal (but not non-verbal) items. In contrast, DAT patients had impairments also in effortful on-line encoding and retention of verbal and nonverbal items. Conclusions: PPA selectively interferes with spontaneous on-line encoding and subsequent retrieval of verbal information. This combination may underlie poor memory test performance and is likely to reflect the dysfunction of the left hemisphere language rather than medial temporal memory network.

Verbal and Nonverbal Memory in Primary Progressive Aphasia: The Three Words-Three Shapes Test

Objectives:To investigate cognitive components and mechanisms of learning and memory in primary progressive aphasia (PPA) using a simple clinical measure, the Three Words Three Shapes Test (3W3S).Background:PPA patients can complain of memory loss and may perform poorly in standard tests of memory. The extent to which these signs and symptoms reflect dysfunction of the left hemisphere language versus limbic memory network remains unknown.Methods:3W3S data from 26 patients with a clinical diagnosis of PPA were compared with previously published data from patients with typical dementia of the Alzheimer type (DAT) and cognitively healthy elders.Results:PPA patients showed two bottlenecks in new learning. First, they were impaired in the effortless (but not effortful) on-line encoding of verbal (but not non-verbal) items. Second, they were impaired in the retrieval (but not retention) of verbal (but not non-verbal) items. In contrast, DAT patients had impairments also in effortful on-line encoding and retention of verbal and nonverbal items.Conclusions:PPA selectively interferes with spontaneous on-line encoding and subsequent retrieval of verbal information. This combination may underlie poor memory test performance and is likely to reflect the dysfunction of the left hemisphere language rather than medial temporal memory network.

Abnormal temporal dynamics of visual attention in Alzheimer's disease and in dementia with Lewy bodies

Although attentional control processes are disproportionately impaired in dementia with Lewy bodies (DLB) compared with dementia of the Alzheimer type (DAT), previous studies have not compared directly the temporal dynamics of visual attention in DLB and DAT. We examined the magnitude of the attentional blink (AB) effect in these patients, to determine the degree to which each patient group exhibited a deficit in selecting and processing visual stimuli presented in rapid succession. Eighteen DAT, 15 DLB patients, and 33 elderly controls were tested in a rapid serial visual presentation task. Participants were asked to report 1 (single-target condition) or 2 target letters (dual-target condition) embedded in a sequence of digit distracters. The temporal dynamics of visual attention was examined by varying the number of intervening distracters between the 2 targets in the dual-target condition and by estimating the attentional blink effect as the decline in the ability to report the second target correctly after successfully identifying the first. Patients with DLB performed significantly worse than patients with DAT and controls in both the single and dual-targets conditions. In contrast, DAT patients showed a selective impairment in the dual-target condition as compared with controls. As predicted, we found that both patients with DAT and DLB showed a more pronounced and protracted attentional blink than controls, indicating a reduced ability to re-engage attention on the second target. Furthermore, when DAT and DLB patients were able to report the second target, they frequently failed to identify the first, an effect that was absent in elderly controls and particularly large and long-lasting in DLB patients. This study suggests that both DLB and DAT patients show abnormal temporal dynamics of visual selective attention, presumably due to a greater intertarget competition for limited processing capacity. More generally, these findings reinforce the notion that deficits of attentional control processes are more severe in DLB patients as compared with DAT patients.

Emotional Recognition from Face, Voice, and Music in Dementia of the Alzheimer Type

Persons with dementia of the Alzheimer type (DAT) are impaired in recognizing emotions from face and voice. Yet clinical practitioners use these mediums to communicate with DAT patients. Music is also used in clinical practice, but little is known about emotional processing from music in DAT. This study aims to assess emotional recognition in mild DAT. Seven patients with DAT and 16 healthy elderly adults were given three tasks of emotional recognition for face, prosody, and music. DAT participants were only impaired in the emotional recognition from the face. These preliminary results suggest that dynamic auditory emotions are preserved in DAT.

Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma cortisol levels

The activity of the hypothalamus-pituitary-adrenocortical (HPA) axis was explored in 10 patients with dementia of the Alzheimer type (DAT) and in 11 age-matched controls, by measuring 1) corticotropin-releasing factor (CRF) levels in cerebrospinal fluid (CSF), 2) the circadian changes of plasma cortisol, 3) and 4) the plasma cortisol response to dexamethasone suppression test (DST) and to CRF stimulation test. CSF CRF levels in DAT were significantly higher than in controls and inversely related to the Mini Mental State (MMS) score. The patients also displayed increased morning (0800 h) plasma cortisol values, with higher mesor and amplitude in the circadian pattern. Dexamethasone resistance was shown by 6 of the 10 DAT subjects. Plasma cortisol response to CRF administration was similar in the two groups, except for the peak values, which in DAT patients were reached earlier than in controls. The present data suggest an overactivity of HPA axis in DAT; its possible role in the evolution of the disease is discussed.

Evidence for a dissociation of structural and semantic knowledge in dementia of the Alzheimer type (DAT)

Object recognition and naming deficits in dementia of the Alzheimer type (DAT) have typically been attributed to deficits in semantic processing, with only a few studies proposing loci of deficits other than semantic. One possible cause of DAT object recognition impairments could involve deficits in processing structural aspects of visually presented items. In this paper, we assess the performance of a group of mild DAT patients on two tasks of structural access, object decision, and the complete/incomplete task (based on part-whole matching task), as well as on a semantic probes task, designed to assess the patients’ semantic knowledge of the same items for which structural knowledge had earlier been assessed. The DAT patients were substantially impaired in their performance on tasks of structural access. Further, no evidence for item-to-item consistency in the DAT patients’ errors for the structural and semantic tasks was found, raising the possibility that structural and semantic knowledge may become differentially impaired in DAT.

Age of Acquisition Affects Object Recognition and Naming in Patients with Alzheimer's Disease

Twenty-two patients with a diagnosis of dementia of the Alzheimer type (DAT) and a comparison group of 22 age-matched individuals took part in an object decision and picture naming task. The age of acquisition (AoA) of the picture names was manipulated (25 early, 25 late). The comparison group identified significantly more objects as real than the patients. While the comparison group made very few errors in object decision, DAT patients failed to classify significantly more late than early acquired objects as real. The patients also named significantly fewer pictures than the comparison group, showing a differential impairment in naming late acquired objects. Late acquired objects induced proportionately more visual errors in the patients than did early acquired objects. The results are discussed in terms of current theories of age of acquisition and of the impact of Alzheimer's disease on lexical and semantic processing.

Error processing in patients with Alzheimer's disease

Patients with dementia are prone to make errors while they perform a task. To evaluate error detection and action monitoring in patients with dementia of the Alzheimer type (DAT) at a relatively early stage of the illness, error negativity (Ne) and error positivity (Pe) of event-related potentials (ERPs) obtained by averages time-locked to error response were studied using a lexical recognition paradigm composed of Japanese ‘kanji’ ideogram characters. In the DAT patients, reaction times were significantly slower and error rates were higher. Not only in healthy elderly subjects but also in the DAT patients, the Ne component obtained by averages time-locked to error response showed a larger amplitude than negativity for correct response (Nc). The Ne and Pe amplitudes were significantly smaller for the DAT patients than for the healthy elderly subjects, whereas there were no significant differences in the Nc amplitude between the two subject groups. Latencies of the Ne, Pe and positivity for correct response (Pc) were prolonged in the DAT patients. These findings suggest that information processing and error detection are slower and somewhat impaired at a relatively early stage of DAT, although error detection and awareness are still preserved.

Insulin and the CNS: effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans

Insulin is mainly known for its peripheral effects on the metabolism of glucose, fats, and proteins. However, insulin also exerts important actions within the brain, and functions as a neuropeptide. The brain can thus be regarded as both an insulin-sensitive and a glucose-sensitive organ. Its neuroanatomical basis is the localization of insulin receptors, predominantly in the olfactory bulbs, hypothalamus, and hippocampus. Data obtained in animal experiments reveal an interesting insulin profile in the brain. Central insulin affects glucoregulation. As long as peripheral euglycemia is maintained, it was shown to reduce food intake and body weight and to improve learning and memory. Cognitive dysfunctions in dementia of the Alzheimer type (DAT) are associated with insulin deficiency within the brain, and memory improves in DAT patients when insulin levels increase. After describing these actions of insulin in the brain, we address here the transport of insulin into the brain. Insulin can either be transported from the periphery to the brain, or be administered directly into the brain. To reach insulin receptors directly, animals are typically administered insulin via the cerebral ventricles. For humans, the intranasal route is a practicable way to reach the brain while maintaining euglycemia. Additionally, the localization of insulin receptors in the olfactory bulb makes insulin interesting for the nose-to-brain pathway. Promising initial results have been reported with intranasally administered insulin corresponding to the diverse actions of insulin in the brain. Interestingly, initial data indicate that states of central insulin deficiencies (DAT and obesity) are accompanied by olfactory deviations. Thus, the nose-to-brain pathway deserves further attention.

Loss of high-level perceptual knowledge of object structure in DAT

Visual object recognition and naming deficits in patients with dementia of the Alzheimer type (DAT) have typically been attributed to deficits in semantic processing. On a visual object naming test, a group of 10 mild, early stage DAT patients (mean MMSE = 23.8) were found to suffer from anomia, compared to a group of 10 age-matched control participants. DAT naming errors were typically within category (commission), associative or circumlocutory errors. Performance on tests of low level visuo-spatial ability fell within the normal range. Together these results suggested that anomia resulted from a dysfunctional semantic system with intact visual perception. However, in a naming task using visually degraded images of familiar objects, the recognition threshold in DAT patients was significantly higher, indicating the need for a more visually complete object representation, before it could be accurately recognised. In a matched task using words visually degraded in an identical manner, the recognition threshold for DAT patients was very similar to that of the control group. It is argued that these results support the idea that impaired structural descriptions of objects (i.e., pre-semantic representation of an object within the visual perceptual system) combines with degraded semantic representations to produce anomia in mild early stage DAT.

Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type

Memory impairment is a process associated with alterations in neuronal plasticity, synapses formation, and stabilization. As the neural cell adhesion molecule (NCAM) plays a key role in synaptic bond stabilization, we analyzed the usefulness of soluble NCAM isoforms in the diagnosis of patients with dementia of the Alzheimer type (DAT). NCAM was measured in the sera of 70 control subjects and 43 DAT patients (with different severity of cognitive impairment, GDS), employing Western blot and densitometric quantification. LMW-NCAM bands (100–130 kDa) decreased significantly with age independently of sex. DAT patients presented values of LMW-NCAM and HMW-NCAM significantly higher than healthy controls of similar age (higher than 130 kDa). Only LMW-NCAM was associated with GDS. Our results suggest that NCAM could be involved in the pathogenesis of DAT disorder and that serum NCAM levels could be useful as differential diagnostic markers of the disease.

Recognition of Facial Expressions and Emotional Situations in Patients with Dementia of the Alzheimer and Vascular Types

The aim of this study was to investigate the ability of patients with dementia to recognize facial expressions and emotional situations. We evaluated 16 patients with dementia of the Alzheimer type (DAT) and 15 with vascular dementia (VD) for general cognition, discrimination of facial expressions and individual faces, and recognition of facial expressions and emotional situations. VD patients performed significantly worse than DAT patients at recognizing facial emotions, even though there was no difference between them in their general cognition and visuoperceptual abilities. There was no significant difference between them in their ability to recognize emotional situations. The results of this and past studies suggest that caregivers in nursing homes and hospitals need to be aware that VD patients lose the ability to comprehend facial expressions.

Effect of manipulation and irrelevant noise on working memory capacity of patients with Alzheimer's dementia.

The effect of manipulation and distracting noise on immediate serial recall was measured in patients with dementia of the Alzheimer type (DAT), neurologically healthy elderly individuals, and young adults. In Experiment 1, the authors compared serial word recall with word recall in alphabetical order. Alphabetical recall requires the active manipulation of the contents of working memory. Findings indicated that DAT patients were severely impaired in the alphabetical recall task, whereas the performance of neurologically healthy elderly participants was comparable with the performance of young adult participants. In Experiment 2, the authors investigated the effect of different irrelevant auditory backgrounds on immediate digit recall. In this task, both elderly participants and DAT patients performed similarly to the group of young adult participants, indicating comparable efficacy to resist auditory distraction.

Vascular dementia among elderly Arabs in Wadi Ara

Dementia of the Alzheimer type (DAT) and vascular dementia (VaD) are the two major subtypes of dementia. In our epidemiological study of DAT in an Arab community in Wadi Ara, Israel, we found a high prevalence of late onset DAT. Illiteracy, smoking, diabetes mellitus (DM) and hypertension are very frequent in Wadi Ara. These factors led us to study the prevalence of VaD and various risk factors in this population. All people aged 60 years or older ( n=823) in a defined region were examined for identification of DAT and VaD (DSM-IV criteria), using clinical examinations and a semi-structured questionnaire for detecting cognitive dysfunction. We identified 49 demented patients (29 males) fulfilling criteria of VaD with a prevalence rate of 49/823 (5.9%), compared to 168/823 (20.5%) for DAT. All had suffered from strokes. Male gender and hypertension were more common among VaD cases. Illiteracy was significantly more common among VaD patients than among healthy subjects (79.6% vs. 40.2%, P=0.001) but less common than among DAT patients (94.6%, P=0.001). Thus, our results show that VaD constitutes about 22% of the total dementia population in Wadi Ara. We confirm the association between VaD, illiteracy and hypertension. Smoking and gender do not represent risk factors for VaD in this population. While suggestive, DM is not a statistically significant risk factor for VaD.

Genetic and environmental risk factors for Alzheimer's disease in Israeli Arabs.

We studied the genetic and environmental risk factors and prevalence, and incidence of dementia of the Alzheimer type (DAT) among the elderly in an Arab community in Israel. Epidemiological and genetic studies of dementia have rarely been reported in an Arab population. All persons aged 60 years or older who were residents of the rural area of Wadi Ara were examined for identification of DAT, vascular dementia (VaD) and conversion from age related cognitive decline (ARCD) to DAT using DSM-IV criteria and a semi-structured questionnaire for collection of demographic and medical data. ApoE genotype was also determined. Total plasma homocysteine (tHcy) was determined using HPLC with fluorescence detection. Vitamins B12 and plasma folate were determined using a commercial radioisotope dilution kit assay (ICN). DAT was diagnosed in 20.5% of this population. Its prevalence increased steeply with age. Illiteracy was very common, and strongly associated with higher prevalence of DAT. The annual incidence of DAT among ARCD cases was 4.4%. Subjects with ARCD who developed DAT were older than ARCD subjects who did not develop dementia. Hypertension was significantly more common among converted patients than among non-converted. Illiteracy was insignificantly more common among those who developed DAT than among those who remained ARCD. Vascular dementia (VaD) constitutes about 22% of the total dementia population. We also confirm the association between VaD, illiteracy and hypertension. Smoking did not represent a risk factor for VaD. The survival rates among the three groups (healthy subjects, ARCD and DAT) was 80.5%, 58.8% and 55.5% respectively. Homocysteine levels were significantly higher than found in studies in Cleveland. Plasma B12 and plasma folate levels did not differ significantly between DAT patients and controls after adjusting for year of birth. Our findings suggest that the Wadi Ara population is unique because of high prevalence rates of dementia. We found old age, female gender and lack of education to be risk factors for the development of DAT. The ApoE epsilon4 allele is relatively uncommon in this population and it cannot explain the high DAT prevalence. We also confirm the association between VaD, illiteracy and hypertension and older age and hypertension are risk factors for the transformation of ARCD to DAT.

Executive function deficits in patients with dementia of the Alzheimer’s type: A study with a Tower of London task

A growing number of studies report a deterioration of the executive function (EF) in dementia of the Alzheimer type (DAT). To evaluate EFs in DAT, a new version of the Tower of London (TOL) task, originally developed by Shallice (1982), was adapted. The new version of the test was built up in its easiest possible feature in order to be administrable to early- or middle-stage demented patients. Seventeen DAT patients, and 17 controls matched for age and sex, were administered the TOL. The protocol followed a “hierarchical paradigm,” that is, simpler problems were embedded in more complex, subsequent problems. Results showed that DAT patients were impaired compared to controls. Both control and DAT groups showed a decrease in percentage of success rate in relation to the number of movements required by the task. On the more complex problems, the performance of DAT subjects was proportionally more impaired. Qualitative analysis revealed that rule breaking was a salient performance feature of the DAT group. These findings are consistent with the presence of an EF deficit in DAT.

Executive function deficits in patients with dementia of the Alzheimer's type A study with a Tower of London task

A growing number of studies report a deterioration of the executive function (EF) in dementia of the Alzheimer type (DAT). To evaluate EFs in DAT, a new version of the Tower of London (TOL) task, originally developed by Shallice (1982), was adapted. The new version of the test was built up in its easiest possible feature in order to be administrable to early- or middle-stage demented patients. Seventeen DAT patients, and 17 controls matched for age and sex, were administered the TOL. The protocol followed a "hierarchical paradigm," that is, simpler problems were embedded in more complex, subsequent problems. Results showed that DAT patients were impaired compared to controls. Both control and DAT groups showed a decrease in percentage of success rate in relation to the number of movements required by the task. On the more complex problems, the performance of DAT subjects was proportionally more impaired. Qualitative analysis revealed that rule breaking was a salient performance feature of the DAT group. These findings are consistent with the presence of an EF deficit in DAT.

Hippocampal structure and the action of cholinomimetic drugs

AbstractCholinomimetic drugs have become the clinical standard for the treatment of patients with dementia of the Alzheimer type (DAT). However, uncertainty remains as to the proportion of patients that respond to such drugs, and how one might predict the capacity for response before treatment is begun. The thesis of the present review is that the neuroanatomical integrity of the hippocampus determines, at least in part, the capacity of DAT patients to respond to cholinomimetic drugs. Neuroimaging studies suggest that volume losses and other neuroanatomical deformities of the hippocampus are common in patients with even mild DAT. Moreover, more severe neuroanatomical deformities of the hippocampus are associated with more severe dementia symptoms and more rapid clinical decline. Animal research, including studies of cholinergic antagonists, glutamatergic antagonists, hippocampal lesions, and animals with mutant amyloid precursor protein genes, demonstrate that behavioral abnormalities similar to those found in DAT patients, especially those related to memory, are associated with hippocampal pathology. Cholinomimetic drugs, in particular, the cholinesterase inhibitors, have been shown to reverse some but not all of these behavioral abnormalities. More research is needed in DAT patients to determine whether an analysis of hippocampal structure or function can reliably predict the outcome of treatment with cholinomimetic drugs. Further work in animals is also needed to determine the limitations of cholinomimetic drugs for reversing various types of cognitive deficits, and to develop and test other pharmacological strategies for the treatment of DAT. Drug Dev. Res. 56:531–540, 2002. © 2002 Wiley‐Liss, Inc.