Mild Dementia Of Alzheimer Type Research Articles

Cognitive impairment in elderly patients suffering from Alzheimer's disease

The purpose of the study: to study destructive forms of cognitive impairment in old age. Materials and methods. A study of 38 people was conducted, of which 16 were men and 22 were women. The control sample consists of 23 people, of which 8 are men and 15 are women. The definition of the control sample was based on the fact that this category of people had cognitive impairments that are the result of other age-related changes that are not the result of AD, whereas the experimental sample needed to have cognitive impairments that are the result of AD. The experimental sample consisted of 15 people, 7 men, 8 women. In the process of MMSE testing, 6 subjects (15.8%) entered the first group, 10 subjects (26.3%) entered the second group, and 22 (57.9%) entered the last group. 42.1% of respondents had mild Alzheimer's type dementia, while 57.9% of respondents had cognitive impairment due to age-related changes. According to the indicators obtained by the method of the short scale of assessment of mental status (Mini-Mental State Examination, MMSE), it can be concluded that memory, attention and orientation in time and space are primarily reduced. Data on the Frontal Dysfunction Battery (FAB) technique showed the absence of a grasping reflex in 29 out of 38 subjects (76.3%), so the presence of a grasping reflex most often indicates a severe degree of Alzheimer's type dementia.

Should Canadian patients look forward to aducanumab for Alzheimer disease?

KEY POINTS In Canada, 190 000 people are living with mild Alzheimer-type dementia and 532 000 to 799 000 people are living with amnestic mild cognitive impairment.[1][1]–[4][2] Developing treatments for Alzheimer disease is challenging, with few effective therapies that only target symptoms.

Association of Stressful Life Events with Dementia in North Indian Populations.

Chronic stress is known to be associated with dementia. This study looked for major stressors and their associations with dementia in the elderly demented population. Case group consisted of 60 subjects (age group 55-75 years; M:F = 7:3) with postscreening for mild cognitive impairment (MCI) and mild Alzheimer's type dementia. Control group consisted of two subgroups: related (N = 60) and not-related (N = 60) subjects screened and confirmed not to be suffering from cognitive impairment. Sociodemographic variables were collected using a personal data sheet. The severity of cognitive impairment was assessed using the Clinical Dementia Rating (CDR) Scale. Subjects with a CDR score of range 0.5-1 were included in mild cognitive impairment and mild Alzheimer's type dementia. Stressful life events were evaluated using the Presumptive Stressful Life Event Scale (PSLES). A present stress level of caregivers was evaluated using Depression Anxiety Stress Scales (DASS). Assessed stress level scores were compared and validated with serum and plasma levels of cortisol and ACTH respectively. Different groups exhibited distinct PSLES and DASS scores with statistical significance. It was also observed that Cortisol and ACTH levels were elevated in case group as compared with that of both sub-group controls. The outcome measures of this study projected that neural degeneration leading to mild cognitive impairment and dementia may be due to accumulative cortisol hormone associated with stressful life events.

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.

Impaired information sampling in mild dementia of Alzheimer’s type but not in healthy aging.

It is unknown whether aging affects predecisional processing, that is, gathering information and evaluating options before making a decision. Here, we investigated information sampling in mild Dementia of Alzheimer's type (DAT) and healthy aging by using the Information Sampling Task (IST). In a first investigation, we compared patients with mild DAT (n = 20) with healthy controls (n = 20) on the IST and several neuropsychological background tests. In a second investigation, healthy older adults (n = 30) were compared with younger adults (n = 30) on the IST and executive-function tasks. Results of the first investigation demonstrated that, in the IST, patients gathered significantly less information, made riskier and less accurate decisions, and showed less reward sensitivity relative to controls. We found a significant correlation between performance on the IST and performance on tests of verbal fluency, working memory, and recognition in patients but not in controls. Results of the second investigation indicated a largely similar performance pattern between healthy older adults and younger adults. There were no significant correlations for both groups between the IST and executive-function tasks. There are no relevant changes with healthy aging in predecisional processing. In contrast, mild DAT significantly affects predecisional information sampling. Thus, the problems shown in patients with mild DAT in decision making might be related to the patients' difficulties in predecisional processing. Decision-making performance in mild DAT might be improved by helping the patients at a predecisional stage to gather sufficient information and evaluate options more accurately.

Diagnostic accuracy of the Phototest for cognitive impairment and dementia in Argentina

Phototest is a simple, easy and very brief test with theoretical advantages over available dementia screening tests in Spain. The objective of this study was to estimate the diagnostic accuracy of the Phototest for cognitive impairment and dementia and to compare it with that of the MMSE and the Clock Drawing Test (CDT) in an Argentine population. A phase II cross-sectional study of diagnostic tests evaluation was performed in a sample of 30 controls, 61 with amnestic mild cognitive impairment (a-MCI), and 56 with mild Alzheimer type dementia (DAT). The diagnostic accuracy (DA) was assessed in relation to the clinical diagnosis by calculating the area under the ROC curve (UAC), Sensitivity (Sn), and Specificity (Sp).The DA of the Phototest for a-MCI and DAT (0.93 and 0.97 [UAC]) was higher than that of the MMSE and the CDT. The cut-off points of 27/28 for DAT (Sn = 89.29 [78.1–96.0], Sp = 96.67 [82.8–99.9]) and 30/31 for a-MCI (Sn = 85.25 [73.8–93.0], Sp = 90.00 [73.5–97.9]) maximized the sum of Sn and Sp. Phototest correlates significantly with MMSE and CDT. The Phototest is an efficient instrument for the detection of mild dementia or MCI, with good accuracy and good correlation with tests measuring overall cognitive impairment.

Metric Distances between Hippocampal Shapes Indicate Different Rates of Change over Time in Nondemented and Demented Subjects

In this article, we use longitudinal morphometry (shape and size) measures of hippocampus in subjects with mild dementia of Alzheimer type (DAT) and nondemented controls in logistic discrimination. The morphometric measures we use are volume and metric distance measures at baseline and follow-up (two years apart from baseline). Morphometric differences with respect to a template hippocampus were measured by the metric distance obtained from the large deformation diffeomorphic metric mapping (LDDMM) algorithm. LDDMM assigns metric distances on the space of anatomical images, thereby allowing for the direct comparison and quantization of morphometric changes. We also apply principal component analysis (PCA) on volume and metric distance measures to obtain principal components that capture some salient aspect of morphometry. We construct classifiers based on logistic regression to distinguish diseased and healthy hippocampi (hence potentially diagnose the mild form of DAT). We consider logistic classifiers based on volume and metric distance change over time (from baseline to follow-up), on the raw volumes and metric distances, and on principal components from various types of PCA analysis. We provide a detailed comparison of the performance of these classifiers and guidelines for their practical use. Moreover, combining the information conveyed by volume and metric distance measures by PCA can provide a better biomarker for detection of dementia compared to volume, metric distance, or both.

Dopamine D3 Receptor Gene Polymorphism Influences on Behavioral and Psychological Symptoms of Dementia (BPSD) in Mild Dementia of Alzheimer's Type

Dopamine D3 receptor (DRD3) is present in the limbic system, which is thought to regulate affect, cognition, and activity. Thus a functional change in the DRD3 gene could in turn affect the cognitive and psychiatric symptoms of dementia of Alzheimer's type (DAT). We investigated a possible association of DRD3 genotype with DAT and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for DRD3 and apolipoprotein E (ApoE) was determined using restriction fragment length polymorphism in 210 patients with mild DAT and 224 age- and sex-matched non-demented controls. The occurrence of BPSD during the course of mild dementia was demonstrated using the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). No significant differences in DRD3 genotype were identified between DAT and controls, regardless of ApoE epsilon4. Among the DAT with BPSD, however, a significant association was observed between the presence of the DRD3 glycine allele and paranoid and delusional ideation, regardless of ApoE epsilon4. In conclusion, DRD3 gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of paranoid and delusional ideation during the course of mild DAT.

Impact of ambiguity and risk on decision making in mild Alzheimer's disease

Decisions under ambiguity and decisions under risk are crucial types of decision making in daily living at any age. This is the first study assessing these two types of decisions in patients with mild dementia of Alzheimer's type (DAT) by means of the Iowa Gambling Task (IGT) and a newly developed, Probability-Associated Gambling (PAG) task. While rules for gains and losses are implicit in the IGT, in the PAG task rules are explicit and winning probabilities, which change from trial to trial, can be estimated. Results of the IGT indicated that DAT patients made more disadvantageous decisions than healthy controls. Patients also shifted more frequently among decks, i.e. under ambiguity decisions were taken randomly and no advantageous strategy was established over time by DAT patients. Thus, not only actual choices but also development of advantageous strategies may be revealing about decision making in the IGT. Compared to controls, patients demonstrated less advantageous choices in the PAG task as well. They gambled more often in the low winning probabilities and less frequently in the high probabilities than healthy participants. Patients’ performance on both tasks correlated with measures of executive functions. Findings of the present investigation are consistent with the early pathological cerebral changes and related (cognitive, emotional) deficits reported for DAT. As suggested by our study, decisions under ambiguity as well as decisions under risk are impaired in mild DAT. It may thus be expected that patients with mild DAT have difficulties in taking decisions in every-day life situations, both in cases of ambiguity (information on probability is missing or conflicting, and the expected utility of the different options is incalculable) and in cases of risk (outcomes can be predicted by well-defined or estimable probabilities).

IDE Gene Polymorphism Influences on BPSD in Mild Dementia of Alzheimer's Type

Insulin degrading enzyme (IDE) degrades amyloid β (Aβ), which may inhibit the accumulation of Aβ in a brain affected with dementia of Alzheimer's type (DAT). A decrease in the activity of IDE results in changes in glucose utilization in the brain, which could affect the cognitive and psychiatric symptoms of DAT. We investigated a possible association of IDE gene polymorphism and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for IDE and apolipoprotein E (ApoE) was determined in 207 patients with mild DAT and 215 controls. The occurrence of BPSD was demonstrated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). IDE gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of affective disturbance through the course of mild DAT, regardless of the presence of an ApoE ε4 allele. The present data could be the result of a small sample size. Further investigations using larger samples are thus required to clarify the correlation between IDE gene polymorphism, susceptibility to DAT, and emergence of BPSD.

Decision-making with explicit and stable rules in mild Alzheimer's disease

Decision-making in mild dementia of Alzheimer's type (DAT) was assessed in a gambling task with stable and explicit rules [Game of Dice Task; Brand, M., Labudda, K., Kalbe, E., Hilker, R., Emmans, D., Fuchs, G., et al. (2004). Decision-making impairments in patients with Parkinson's disease. Behavioural Neurology, 15, 77–85]. DAT patients in an early stage of the disease chose safe alternatives as frequently as healthy elderly persons and did not show risky behaviour as has been reported for other neurological patient groups. However, a more detailed analysis disclosed important differences between DAT and healthy elderly. Compared to healthy controls, DAT patients shifted more frequently between safe and risky alternatives and showed less consistent response patterns. Frequent changes between strategies indicate that decisions were taken randomly, that no advantageous strategy was established and that no consistent response pattern was developed over time. As regards performance changes over the task, healthy participants had a stronger tendency towards safe and advantageous responses than DAT patients. While healthy controls showed learning as the task proceeded, DAT patients did not adapt their strategies. The proportion of “consistently safe responders” was significantly higher in the control group than in the DAT group. Analysis of reaction times indicated that differences in response behaviour were not due to fast and impulsive decision taking in the DAT group. DAT patients’ response pattern may be attributed to deficits in learning and in executive functions. The frequency of changes between safe and risky choices proved to be a fair predictor for the distinction between mild DAT and healthy aging.

Plasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia

Studies of subjects with dementia of the Alzheimer type have reported correlations between increases in activity of the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal degeneration. In this study, the authors sought to determine whether increases in plasma cortisol, a marker of HPA activity, were associated with clinical and cognitive measures of the rate of disease progression in subjects with Alzheimer-type dementia. Thirty-three subjects with very mild and mild Alzheimer-type dementia and 21 subjects without dementia were assessed annually for up to 4 years with the Clinical Dementia Rating scale and a battery of neuropsychological tests. Plasma was obtained at 8 a.m. on a single day and assayed for cortisol. Rates of change over time in the clinical and cognitive measures were derived from growth curve models. In the subjects with dementia, but not in those without dementia, higher plasma cortisol levels were associated with more rapidly increasing symptoms of dementia and more rapidly decreasing performance on neuropsychological tests associated with temporal lobe function. No associations were observed between plasma cortisol levels and clinical and cognitive assessments obtained at the single assessment closest in time to the plasma collection. Higher HPA activity, as reflected by increased plasma cortisol levels, is associated with more rapid disease progression in subjects with Alzheimer-type dementia.

Plasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia

Objective: Studies of subjects with dementia of the Alzheimer type have reported correlations between increases in activity of the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal degeneration. In this study, the authors sought to determine whether increases in plasma cortisol, a marker of HPA activity, were associated with clinical and cognitive measures of the rate of disease progression in subjects with Alzheimer-type dementia. Method: Thirty-three subjects with very mild and mild Alzheimer-type dementia and 21 subjects without dementia were assessed annually for up to 4 years with the Clinical Dementia Rating scale and a battery of neuropsychological tests. Plasma was obtained at 8 a.m. on a single day and assayed for cortisol. Rates of change over time in the clinical and cognitive measures were derived from growth curve models. Results: In the subjects with dementia, but not in those without dementia, higher plasma cortisol levels were associated with more rapidly increasing symptoms of dementia and more rapidly decreasing performance on neuropsychological tests associated with temporal lobe function. No associations were observed between plasma cortisol levels and clinical and cognitive assessments obtained at the single assessment closest in time to the plasma collection. Conclusions: Higher HPA activity, as reflected by increased plasma cortisol levels, is associated with more rapid disease progression in subjects with Alzheimer-type dementia.

Increased frontal phase-locking of event-related theta oscillations in Alzheimer patients treated with cholinesterase inhibitors

This is a pilot study describing event-related oscillations in patients with Alzheimer-type dementia (AD). Theta responses of 22 mild probable AD subjects according to NINCDS-ADRDA criteria (11 non-treated, 11 treated by cholinesterase inhibitors), and 20 healthy elderly controls were analyzed by using the conventional visual oddball paradigm. We aimed to compare theta responses of the three groups in a range between 4–7 Hz at the frontal electrodes. At F 3 location, theta responses of healthy subjects were phase locked to stimulation and theta oscillatory responses of non-treated Alzheimer patients showed weaker phase-locking, i.e. average of Z-transformed means of correlation coefficients between single trials was closer to zero. In treated AD patients, phase-locking following target stimulation was two times higher in comparison to the responses of non-treated patients. The results indicate that the phase-locking of theta oscillations at F 3 in the treated patients is as strong as the control subjects. The F 4 theta responses were not statistically significant between the groups. Our findings imply that the theta responses at F 3 location are highly unstable in comparison to F 4 in non-treated mild AD patients and cholinergic agents may modulate event-related theta oscillatory activities in the frontal regions.

Prepulse inhibition of acoustic startle response in mild cognitive impairment and mild dementia of Alzheimer type

Amnestic mild cognitive impairment (MCI) describes the condition of memory-impaired individuals who otherwise function well and do not meet the clinical criteria for dementia. Such individuals are considered to represent a transitional stage between normal aging and dementia of Alzheimer type (DAT). Neurobiologic changes in amnestic MCI, and their significance for psychophysiologic function, are poorly understood. In this study, the authors compared acoustic prepulse inhibition (PPI) between subjects with amnestic MCI and mild DAT to characterize sensorimotor gating. The acoustic startle reflex, which the authors measured using an accelerometer and electromyogram, involves whole-body movement and eye blink in response to a sudden loud noise (115 dB). PPI is inhibition of this reflex by a softer noise (prepulse; 85 dB) preceding the startle stimulus by 30 ms. PPI was examined in 30 controls, 20 subjects with amnestic MCI, and 20 subjects with mild DAT. Neither amnestic MCI nor mild DAT affected startle movement amplitude. Subjects with amnestic MCI showed significantly enhanced PPI (gating facilitation), while subjects with mild DAT exhibited significantly less PPI than controls (gating deficit). This pattern of PPI changes suggests that neuropathologic changes in the limbic cortex, mainly the entorhinal cortex, at the earliest stage of DAT might be responsible for PPI abnormalities via disturbed regulation of the limbic cortico-striato-pallido-pontine circuitry. Startle PPI changes could be used as a biologic marker for amnestic MCI and mild DAT.

Possibility of Objective Diagnosis in Patients with Mild Alzheimer-type Dementia

Possibility of Objective Diagnosis in Patients with Mild Alzheimer-type Dementia

Pushing and pulling with the upper extremities while standing: the effects of mild Alzheimer dementia and Parkinson's disease.

Eleven patients with mild dementia of Alzheimer type, 12 patients with mild to moderate Parkinson disease, and 27 control subjects of comparable age, education, and gender pushed or pulled on a rigid horizontal bar while maintaining stable erect stance. A target window (target force +/-10% maximum force) and a bar force cursor were displayed on a video screen, and subjects were asked to place the bar force cursor within the target window as quickly and as accurately as possible holding the target window for at least 1 sec. The target forces were 50% and 75% maximum force for each person, and three 4.0-sec push trials and three 4.0-sec pull trials were performed for each target force. Moments of force (torque), body motion, and extremity electromyography were measured with a computerized motion analysis system. The patients with Alzheimer's disease had only slightly lower Mini Mental State Examination (MMSE) scores (mean +/- standard deviation [SD] = 25.0 +/- 2.3) than the patients with Parkinson's disease (28.8 +/- 1.5) and control subjects (28.7 +/- 1.3). The patients with Alzheimer's disease had upper limb reaction times (0.827 +/- 0.399 sec) that were greater than those of the patients with Parkinson's disease (0.672 +/- 0.315 sec) and control subjects (0.606 +/- 0.263 sec). Furthermore, the patients with Alzheimer's disease achieved the designated target in only 46.2% of trials, which was comparable to the performance of the patients with Parkinson's disease (55.6%) but inferior to the control subjects (80.6%). Movement times did not differ significantly. The patients and control subjects initiated movement with comparable anticipatory postural activity in the lower limbs. The poor success rates of the patients with Alzheimer's disease and the patients with Parkinson's disease were attributable to inadequate visually guided adjustments in force after the initial movement began. This difficulty in making quick motor adjustments may be relevant to the tendency of patients with Alzheimer's disease to fall.

Semantic Priming in Patients with Alzheimer and Semantic Dementia

Semantic priming for pairs of words having semantic relation (members of the same category) but not associative relation was tested in four patients with mild Alzheimer-type dementia (AD), three patients with semantic dementia (SD) and three normal controls. Priming effects were exhibited by all the AD patients and normal controls but by none of the SD patients. The facilitation did not differ depending on whether words were written in kanji or kana. The nature of semantic deficits in AD and SD is discussed.

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.

Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type

To study the unawareness of cognitive deficits in patients with mild dementia of Alzheimer type (DAT). Retrospective study. We surveyed the medical records of outpatients meeting the NINCDS-ADRDA criteria for probable DAT who were able to complete the Cognitive Difficulties Scale (CDS) and had a close informant relative (IR) who could complete the family form of the same questionnaire. A department of neurology in a general teaching hospital. Eighty-eight patients, aged 73.2+/-8.6 years with a mean MMSE score of 22.5+/-3.2. Fifty-two of the 88 patients had a follow-up examination after a mean interval of 21 months. Awareness of cognitive deficits was mainly assessed as the difference between the scores on the CDS completed by the IR and the patient (Index of Unawareness, IU). Two secondary assessments of unawareness were performed: (1) an assessment by the clinician on the basis of the patient's answers to questions probing the awareness of memory deficits; (2) an evaluation by the IR of the frequency of behavioural manifestations of unawareness in everyday life. SPECT was performed in 78 patients to study the relationship between unawareness and the topography of perfusion deficits. Awareness of the cognitive deficits varied greatly between patients, according to the assessment method used and the stage of progression of the disease. Most patients with mild DAT were cognitively aware of their cognitive deficits but failed to appraise their severity and their consequences in everyday life. Decreased awareness was positively correlated with age and perfusion deficits in the frontal regions and negatively with the anxious symptomatology. However, the main correlate of unawareness was apathy. The nature of unawareness of cognitive deficits appeared to be more dimensional than categorical. In patients with mild dementia, decreased awareness appeared to be more related to affective disturbances, especially to emotional deficit or apathy, than to cognitive deficits.