Status In Alzheimer's Disease Patients Research Articles

An investigation into the potential association between nutrition and Alzheimer's disease.

Malnutrition is the most common nutritional issue in Alzheimer's disease (AD) patients, but there is still a lack of a comprehensive evaluation of the nutritional status in AD patients. This study aimed to determine the potential association of various nutritional indices with AD at different stages. Subjects, including individuals with normal cognition (NC) and patients diagnosed with AD, were consecutively enrolled in this cross-sectional study. Demographics, body composition, dietary patterns, nutritional assessment scales and nutrition-related laboratory variables were collected. Binary logistics regression analyses and receiver operating characteristic (ROC) curves were used to indicate the association between nutrition-related variables and AD at different stages. Totals of 266 subjects, including 73 subjects with NC, 72 subjects with mild cognitive impairment due to AD (AD-MCI) and 121 subjects with dementia due to AD (AD-D) were included. There was no significant difference in dietary patterns, including Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet between the three groups. Lower BMI value, smaller hip and calf circumferences, lower Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) scores, and lower levels of total protein, albumin, globulin, and apolipoprotein A1 were associated with AD (all p < 0.05). Total protein and albumin levels had the greatest ability to distinguish AD from non-AD (AUC 0.80, 95% CI 0.74-0.84, p < 0.001), increased by combining calf circumference, MNA score and albumin level (AUC 0.83, 95% CI 0.77-0.88, p < 0.001). Albumin level had the greatest ability to distinguish NC from AD-MCI (AUC 0.75, 95% CI 0.67-0.82, p < 0.001), and MNA score greatest ability to distinguish AD-MCI from AD-D (AUC 0.72, 95% CI 0.65-0.78, p < 0.001). Nutritional status of AD patients is significantly compromised compared with normal controls, and tends to be worsened with AD progresses. Early identification and intervention of individuals with nutritional risk or malnutrition may be significantly beneficial for reducing the risk, development, and progression of AD.

Development of SPECT Probes for In Vivo Imaging of β-Amyloid and Tau Aggregates in the Alzheimer's Disease Brain

Alzheimer's disease (AD) is the most common form of irreversible dementia among elderly people. In the postmortem brains of AD patients, the deposition of senile plaques composed of β-amyloid (Aβ) peptides and neurofibrillary tangles composed of highly phosphorylated tau proteins are two neuropathological hallmarks. Therefore, the in vivo imaging of Aβ and tau aggregates with positron-emission tomography (PET) or single-photon emission computed tomography (SPECT) would promote drug development, early diagnosis, and monitoring of the disease status in AD patients. In this study, we designed and synthesized novel Aβ and tau imaging probes for SPECT. [125I]PBOX-3, developed as an Aβ imaging probe, showed high affinity for Aβ aggregates in vitro. A SPECT/CT study with [123I]PBOX-3 revealed a higher level of radioactivity in a Tg2576 mouse, which is the AD model mouse, than in a wild-type mouse. In addition, ex vivo autoradiograms of brain sections from a Tg2576 mouse after the injection of [123I]PBOX-3 showed the selective binding of Aβ plaques. BIP-NMe2, developed as a tau imaging probe, showed high and selective affinity for tau aggregates in AD brain sections. In addition, [125I]BIP-NMe2 displayed high initial uptake into, and fast washout from, the normal mouse brain, suggesting that [125I]BIP-NMe2 has favorable pharmacokinetics for the in vivo imaging of tau aggregates. Taken together, we successfully developed an Aβ imaging probe, PBOX-3, and a tau imaging probe, BIP-NMe2. These probes may be used to develop novel methods for the diagnosis, treatment and monitoring of AD progression.

Vascular Impairment in Alzheimer's Disease: The Role of Obstructive Sleep Apnea

Epidemiological studies have suggested a pathophysiological link between obstructive sleep apnea syndrome (OSAS) and Alzheimer's disease (AD). The mechanism by which sleep disturbance can affect cognitive impairment is not clear. The aim of this study was to investigate whether AD patients with OSAS have an impairment in cerebrovascular disease markers. We included 69 patients without OSAS and 93 patients with OSAS. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). Pathological values of IMT and BHI were significantly associated with the presence of OSAS (IMT > 1.0 mm: OR 2.98, 95%CI: 1.37-6.46; p < 0.05; BHI < 0.69: OR 5.25, 95%CI: 2.35-11.74; p < 0.05, multivariate adjusted analysis). Furthermore, the extent of cerebrovascular impairment was correlated with the severity of OSAS. The finding of alterations of cerebral vessel functional and anatomic status in AD patients with OSAS suggests the potential for effective treatment for sleep-related disturbances in a subgroup of AD patients.

The effect of stress on the antioxidative potential of serum: implications for Alzheimer’s disease

There is growing consensus in the literature that oxidation status is increased in Alzheimer's disease (AD), and that antioxidant supplementation as prevention or treatment strategy should be investigated further. In the present study the total antioxidant status (TAS) was found to be highly significantly lower in 22 AD patients (p < 0.0001) than in 22 age- and gender matched non-demented controls. The TAS was also lower than controls in 22 patients with vascular dementia, but not significantly. The increased oxidation status in AD was verified using the benzoate hydroxylation method. The origin of the enhanced oxidation status in AD has not been elucidated. To determine whether a causal effect between stress and oxidative status of serum can be demonstrated, a rat model was used with two different kinds of stressors, swim stress (exercise) and restraint stress (non-exercise stress). Following swim stress the maximum oxidative effect was observed at one hour post stress (p < 0.001). At 24 h the oxidative status had recovered significantly to below control values. Restraint stress, however, showed progressively increased oxidation which attained significance after 24 h (p < 0.005). It is postulated that stress may contribute to the higher oxidation status in AD patients.

Alzheimer's disease-associated disability: An ICF approach

Purpose. The aim of the study is to provide a description of dementia-associated disability in Alzheimer's disease (AD) patients through the International Classification of Functioning, Disability and Health (ICF).Method. Twenty-six AD patients at different stages of disease participated in the study. Mini Mental State Examination (MMSE) and Global Deterioration Scale (GDS) were used to stage the degree of cognitive impairment and the stage of disease, respectively. All subjects were classified using the ICF categories in the more detailed four-level version. Correlation between compromised ICF items and both MMSE and GDS scores were calculated through Spearman Rho test.Results. Mental functions were impaired in all the subjects examined. Data on activity and participation showed that not only domestic life, self care, and mobility but also communication and interaction and social relationships are compromised in AD patients. Three main areas appeared as the most relevant facilitators: products and technology, support and relationship and services, systems and policies. ICF codes were generally correlated with both MMSE and GDS: subjects who appeared more compromised on MMSE and GDS showed higher impairment of functions, activity limitation, and participation restriction.Conclusion. ICF is a useful tool to describe health status in AD patients in that it underlines important aspects of daily living generally not considered by activity of daily living scales such as communication, social relationships, and recreation and leisure.

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients.

Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.

Neuroanatomical correlates of low body weight in Alzheimer's disease: a PET study

Weight loss is a common problem in patients with Alzheimer's disease (AD) and this might be associated with an increased risk for mortality. Recent evidences have suggested that certain brain dysfunctions may result in impaired nutritional status in AD patients. However, the mechanism of body weight loss in AD remains enigmatic. To investigate a possible association between low body weight and regional brain dysfunction, the authors conducted the correlational analysis of body mass index (BMI) with regional brain glucose metabolism using positron emission tomography (PET) and [ 18F]fluorodeoxyglucose (FDG). Twenty-seven patients with probable AD were divided into two groups: the low BMI group and the normal BMI group. Regional brain glucose metabolic ratios were calculated using the cerebellar hemisphere as a reference region. Comparisons were made of regional brain metabolic ratios between the low BMI group and the normal BMI group. Correlations of the glucose metabolic ratio with BMI were also assessed in all patients with AD. In the comparison between the two groups, glucose metabolic ratio in the anterior cingulate cortex (ACC) was significantly lower in the low BMI group, whereas no significant differences were found in all the other brain regions. Furthermore, regional glucose metabolism in the ACC had a significant and positive correlation with BMI ( r=.450, P=.018). After adjustment for age, gender and disease duration, regional glucose metabolism in the ACC was independently associated with BMI. Our findings suggest that the ACC may be preferentially involved in the regulation of nutritional status in AD patients, and provides a new insight into developing strategies for prevention and treatment of undernutritional demented patients.

A prospective study of chances in the nutritional status of Alzheimer's patients

The evolution of nutritional parameters was studied over 1 year in patients with Alzheimer's disease (AD). Seventy-six community dwelling patients with probable AD underwent a comprehensive nutritional assessment at entry into the study and 1 year later. The nutritional assessment included anthropometric and biological markers, as well as a complete dietary assessment. A comprehensive functional and neuropsychological evaluation was performed on each patient using a number of standardized and validated tools, as well as a scale to evaluate caregiver burden. Just over 44 % of our subjects experienced a greater than 4 % weight loss in 1 year. Over 13 % of our subjects lost more than 10 % body weight. Patients having lost weight resembled patients without weight loss, except that caregiver burden was perceived to be higher in the weight loosing group, they tended to lose independence in activities of daily living (ADL). This group also had a decrease in daily caloric intake (−400 kCal/day). In 1 year, a large number of AD patients lose weight. Given the seriousness of the problems associated with weight loss it seems to be prudent to recommend a regular monitoring of the nutritional status in AD patients, as soon as the diagnosis is suspected, and instituting a weight loss prevention program where caregiver burden is perceived as the greatest.

Clustering of Pathological Features in Alzheimers Disease: Clinical and Neuroanatomical Aspects

We have analyzed the tendency of amyloid load, neuritic plaques and neurofibrillary tangles (NFT) in the hippocampus and neocortex to occur in clusters in 49 consecutive cases of Alzheimer's disease (AD). This clustering tendency of the pathology was analysed in relation to severity of clinical disease assessed within 6 months before death, duration and age at onset of disease and at death. Amyloid plaques showed only a slight tendency to cluster together while neuritic plaques and, even more, NFT were clearly clustered. A greater clustering tendency was associated with more severe clinical impairment with particularly strong correlations being found between the clustering tendency of NFT in the hippocampus and clinical memory deficit, and between the clustering tendency of NFT in the parietal neocortex and overall cognitive deficit. Neuritic plaques showed similar but less pronounced and robust correlations between clustering and cognitive status. In the hippocampus NFT clustering was also negatively correlated with age at death, but not duration of disease nor age of disease onset. We conclude that clustering characterises neuritic pathology but not diffuse amyloid deposits and significantly affects cognition. The discrepancies between the group diagnosed as AD-only and the patient group that contained all patients, including the ones with mixed pathology, lead us to believe that any additional pathology might have a significant effect on the cognitive status of AD patients.

Ion beam analysis of the bone tissue of Alzheimer's disease patients

Abstract It has been hypothesized that perturbations in element metabolism play a role in the etiology and/or pathogenesis of Alzheimer's disease (AD). No conclusion regarding this hypothesis has been reached, however, as results for central nervous system tissues from different research groups are contradictory. We are currently utilizing external-beam thick-target FIXE and PIGE analyses to investigate the elemental concentrations in the bone tissue of AD patients. Because bone acts as a “repository” for many trace elements, these measurements should provide information on the long-term trace-element status of AD patients. With the simultaneous PIXE/PIGE measurements, we are able to instrumentally determine the concentrations of oxygen, phosphorus, calcium, and 12–15 minor and trace elements in a single 30 min irradiation. Initial results obtained from the IBA measurements of both cortical and trabecular bone autopsy samples from four AD patients and twelve age-matched controls indicate a possible imbalance in Zn, Br and Rb.

Suprasellar cistern measures as a reflection of dementia in Alzheimer's disease but not Huntington's disease

Four methods of measuring the suprasellar cistern (SSC), the SSC area ratio, the hexagonal area ratio, the width ratio, and perceptual rating, are described. All four are found to be reliable across raters, time, and procedure (light box vs. computer), and all are able to distinguish Alzheimer's Disease (AD) and Huntington's Disease (HD) patients from their respective age-matched controls. The width ratio, a measure of minimum distance between the two temporal lobes divided by brain width at the same level, was most effective in distinguishing HD from AD patients when age was used as a covariate. Because the width of the SSC measures separation of the temporal lobes at the level of the amygdala and entorhinal cortex, it is reasonable to expect this measure to distinguish between AD and HD, as the amygdala and entorhinal cortex are known to be particularly severely affected in AD, but not in HD, patients. The other measures of SSC were most highly correlated with cognitive status in AD patients. Several possible explanations for this finding are offered. No SSC measure was significantly correlated with cognitive status in HD. This suggests that atrophies of the frontal-temporal and basal forebrain areas are associated with cognitive decline in Alzheimer's Disease but not in Huntington's Disease.