Reduced expression of SIRT1 and SOD-1 and the correlation between these levels in various regions of the brains of patients with Alzheimer's disease

AimsThis study was designed to explore the expression and distribution of silent information regulator 1 (SIRT1) and superoxide dismutase 1 (SOD-1) in various regions of the brains of patients with Alzheimer's disease (AD), as well as to assess potential correlations between the levels of these proteins and also between these proteins and the Braak stage of AD.MethodsIn the temporal and frontal cortices, hippocampus and cerebellum of 10 patients with AD and 10 age-matched control subjects, expression of SIRT1 and SOD-1, together with histopathology, were assessed by immunohistochemical and immunofluorescent stainings. Relationships between variables were examined with the Pearson correlation test.ResultsThe numbers of both SIRT1-positive and SOD-1-positive neurons and integrated optical density of immunohistochemical staining for these proteins in the temporal and frontal cortices, and hippocampus of patients with AD were significantly decreased than those in corresponding controls. In the case of the cerebellum, very weak expression of SIRT1 and obvious expression of SOD-1 were observed in granule cells, with no significant difference between AD and the control group. Interestingly, the protein levels between SIRT1 and SOD-1, as well as the level of SIRT1 or SOD-1 and Braak stage, were significantly correlated in neurons in all regions of the AD brains investigated except for the cerebellum.ConclusionsThese findings indicate that the reduced level of SIRT1 in the brains of patients with AD may be related to the decline in SOD-1 and neuropathological changes of this disorder.

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Adequacy of food consumption in elderly Alzheimer’s disease in a community of Southern Brazil: a Cross-sectional study

F1000Research ◽

10.12688/f1000research.13835.1 ◽

2018 ◽

Vol 7 ◽

pp. 671

Author(s):

Glaucia Renee Hilgemberg ◽

Aline Jacoski de Oliveira Krüger da Silva ◽

Bárbara Luisa Fermino ◽

Camila Diedrich ◽

Simone Carla Benincá ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nutritional Status ◽

Neuronal Loss ◽

Great Difficulty ◽

Amyloid Peptide ◽

Control Group ◽

Food Record ◽

Cross Sectional ◽

Significant Difference

Background: Alzheimer's disease (AD) is the most common cause of dementia, with a multifactorial etiology, in which the person has great difficulty identifying feelings of hunger, satiety, and feeding, which may affect their nutritional status. Pathologically, it is associated with neurodegeneration of synapses followed by neuronal loss, accompanied by glial proliferation surrounded by neurofibrillary tangles, beta-amyloid peptide (Aβ) deposition, inflammation and cerebrovascular injury hindering the ability to perform activities of daily living. This study aimed to analyze quantitatively the differences between an elderly group with AD and a control group, in terms of macro and micronutrient consumption evaluation. Methods: the study involved 69 participants who were assessed via collection of anthropometric measurements (weight, height and body mass index) with nutritional status being assessed by 24-hour food recall and three-day food record. Cognitive assessments were performed using the Mini-Mental State Examination (MMSE) and Clinical Dementia Ranting (CDR). Results: The intake of lipids in patients with severe dementia, was lower (p <0.05). The consumption of proteins showed a decrease with demential advance. For vitamins, there was a significant difference (p <0.05) in the amount of thiamine, niacin, vitamin D, E and K and calcium, chromium and iodine minerals, which were significantly reduced in AD patients (p <0.05). Conclusions: Decreases in macronutrient and micronutrient consumption may result in a consequent impairment of nutritional status, dementia progression, and decreased quality and life expectancy of elderly patients with AD.

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Evaluation of Renal Function in Alzheimer’s Disease and Geriatric Patients: Results from a Turkish Two-Center Study

Journal of Medical Biochemistry ◽

10.1515/jomb-2016-0028 ◽

2017 ◽

Vol 36 (1) ◽

pp. 54-61

Author(s):

Zubeyde Erbayraktar ◽

Ahmet Turan Evlice ◽

Gokhan Yilmaz ◽

Canan Yazici ◽

Gorsev Yener ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Renal Function ◽

Total Protein ◽

Geriatric Patients ◽

Age Groups ◽

Conclusive Evidence ◽

University Hospitals ◽

Protein Levels ◽

Significant Difference

SummaryBackground:Alzheimer’s disease (AD) is a severe multifactorial neurodegenerative proteopathy associated with advanced age. Discrepancies in the renal function of these patients compared to geriatric patients with dementia have rarely been reported. In this study, we aimed to disclose the importance of associated renal changes for the pathogenesis of AD.Methods:Patients with AD (n=107) and geriatric patients with dementia and without dementia (n=124) (231 patients in total) from Dokuz Eylul and Cukurova University Hospitals were enrolled in the study. We measured serum Na, K, Cl, Ca, BUN, creatinine, total protein levels and MDRD [eGFR] in all groups.Results:From Izmir Center, the first study arm consisted of patients with AD dementia (n=74), and the second arm included geriatric patients with dementia (n=79). From Adana, 78 patients were recruited to the study, of which 33 were with AD and 45 were geriatric patients without dementia. When we analyzed comparatively the AD and geriatric dementia patients study arms, a statistically significant difference was observed both in the median age (p<0.001), as well as in the biochemical parameters from Izmir Center: Na (p<0.001), K (p<0.001), Cl (p<0.05), Ca (p<0.001), BUN (p<0.05), creatinine (p<0.001), total protein (p<0.001) and MDRD [eGFR] (p<0.001). However, these were not significantly different between AD and geriatric patients without dementia in the Adana group.Conclusions:Our results indicate that renal function is prone to alterations in different age groups of patients with AD. However, there is no conclusive evidence that renal function is one of the risk factors in AD.

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Serotonin 5-HT2A Receptor Binding in Platelets From Patients With Alzheimer's Disease or Vascular Dementia

International Psychogeriatrics ◽

10.1017/s1041610200006645 ◽

2000 ◽

Vol 12 (4) ◽

pp. 537-545 ◽

Cited By ~ 8

Author(s):

Olav Spigset ◽

Christer Wilhelmsson ◽

Tom Mjörndal ◽

Sture Eriksson

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vascular Dementia ◽

Receptor Binding ◽

Rating Scale ◽

Control Group ◽

Receptor Status ◽

Serotonin System ◽

Significant Difference ◽

Scale Scores

It is well known that abnormalities in the brain serotonin system exist in patients with dementia. The present study was performed in order to investigate whether a peripheral serotonin system marker, the platelet 5-HT2A receptor, is affected in dementia. Thirty-eight patients with Alzheimer's disease (AD), 13 patients with vascular dementia, and 40 healthy controls were included in the study. There were no significant differences in receptor density for 5-HT2A receptor binding between the groups. Affinity of the radioligand to the receptor was significantly lower in AD than in vascular dementia and in the controls (p = .006 and p = .003, respectively), whereas there was no significant difference between the vascular dementia group and the control group. In 12 patients, treatment with citalopram was started due to depression or agitation. This treatment significantly reduced the Behavioral Pathology in Alzheimer's Disease Rating Scale scores (p = .001), but did not affect the platelet 5-HT2A receptor status. There was no correlation between 5-HT2A receptor status before treatment and the therapeutic effect of citalopram. The study indicates that platelet 5-HT2A receptor status is of limited value as a peripheral marker in dementia.

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Testosterone profile in older men with Alzheimer's disease

Dementia & Neuropsychologia ◽

10.1590/s1980-57642009dn20400010 ◽

2008 ◽

Vol 2 (4) ◽

pp. 289-293

Author(s):

Cristiana Roscito Arenella Dusi ◽

Lílian Schafirovits Morillo ◽

Regina Miksian Magaldi ◽

Adriana Nunes Machado ◽

Sami Liberman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Free Testosterone ◽

Older Men ◽

Sex Hormone Binding Globulin ◽

Control Group ◽

Total Testosterone ◽

Chi Square ◽

Testosterone Levels ◽

Significant Difference

Abstract Evidence suggests low testosterone levels in Alzheimer's disease. Objectives: To compare testosterone levels between older men with and without Alzheimer's disease. Methods: Fourteen men with Alzheimer's disease were compared with twenty eight men without dementia. Demographic variables and clinical profiles were analyzed. Within fifteen days before or after the described evaluation, measures of total testosterone and Sex Hormone Binding Globulin (SHBG) were performed. Free testosterone level was calculated based on total testosterone and SHBG. Quantitative variables were analyzed using Student's t test or Kruskal-Wallis test, while qualitative variables were analyzed using chi-square or Fisher test. Results: Mean age in the Control and Alzheimer's disease groups were 72.0 (SD±4.8) years and 79.3(SD±5.9) years, respectively (p=0.001). Mean schooling between these two groups were 8.78 and (±5.86) years, respectively (p=0.022). There were no statistically significant differences between the two groups for testosterone levels, although a trend was observed for the Alzheimer's disease group to present lower levels than the control group (p=0.066). There was no direct correlation between free testosterone and age, although a trend was evident (p=0.068). Conclusions: There was no significant difference in testosterone between men with AD and those without dementia.

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Posturographic analysis of older adults without dementia and patients with Alzheimer’s disease: A cross-sectional study

Dementia & Neuropsychologia ◽

10.1590/1980-57642018dn13-020008 ◽

2019 ◽

Vol 13 (2) ◽

pp. 196-202 ◽

Cited By ~ 1

Author(s):

Paula Sant’Anna ◽

Felipe de Oliveira Silva ◽

Ana Carolina de Mello Alves Rodrigues ◽

Jéssica Plácido ◽

José Vinicius Ferreira ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Postural Control ◽

Effect Size ◽

Control Group ◽

Significant Difference ◽

Global Cognition ◽

Elliptical Area ◽

Total Velocity

ABSTRACT. Additional clinical tools should be investigated to facilitate and aid the early diagnosis of cognitive decline. Postural control worsens with aging and this may be related to pathological cognitive impairment. Objective: to compare the balance of older adults without dementia in a control group (CG) and with Alzheimer’s disease (AD), to observe the possible association with the independent variables (diagnosis, age, gender, and global cognition) and to verify the best posturographic analyses to determine the difference between the groups. Methods: 86 older adults (AD = 48; CG = 38) were evaluated using the Berg Balance Scale (BBS) and postural control was assessed by stabilometry on the Wii Balance Board ® (WBB). Independent T, Mann-Whitney U-tests, Effect Size (ES) and a linear regression were performed. Results: there was a significant difference for Elliptical Area, Total Velocity, Medio-Lateral displacements with closed eyes and open eyes, antero-posterior, with closed eyes and BBS between groups. These variables showed a large effect size for BBS (-1.02), Elliptical Area (0.83) with closed eyes, Medio-Lateral (0.80, 0.96) and Total Velocity (0.92; 1.10) with eyes open and eyes closed, respectively. Regression indicated global cognition accompanied by age, gender, and diagnosis influenced postural control. Conclusion: patients with AD showed impaired postural control compared to Control Group subjects. Total Velocity with closed eyes was the most sensitive parameter for differentiating groups and should be better investigated as a possible motor biomarker of dementia in posturographic analysis with WBB.

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Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Current Alzheimer Research ◽

10.2174/1567205016666190311102130 ◽

2019 ◽

Vol 16 (4) ◽

pp. 293-301

Author(s):

Kiyotaka Nakamagoe ◽

Shiori Yamada ◽

Rio Kawakami ◽

Tadachika Koganezawa ◽

Akira Tamaoka

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Higher Order ◽

Control Group ◽

Order Function ◽

Cortical Damage ◽

Significant Difference ◽

Eyes Open ◽

Proportional Relationship ◽

Saccadic Intrusions

Background: Classified as saccadic intrusions, Square-Wave Jerks (SWJs) have been observed during Visual Fixation (VF) in Alzheimer’s Disease (AD). However, the pathological significance of this phenomenon remains unclear. Objective: The present study analyzed the characteristics of SWJs in patients with AD with their eyes open in the dark without VF. Methods: Fifteen patients with AD and 15 healthy age- and sex-matched controls were investigated and compared. Saccadic intrusions with and without VF were detected as SWJs and measured using an electronystagmogram. Results: No significant difference in the frequency of SWJs was observed between control and AD groups with VF, but significantly more SWJs were observed in the AD group than in the control group in the absence of VF (p<0.01). In the control group, the frequency of SWJs was significantly higher with VF as compared to without VF. Conversely, the frequency in the AD group was significantly higher without VF. Furthermore, a directly proportional relationship was observed between the frequency of SWJs and higher-order function (R>0.55) in the AD group. Conclusion: SWJs without VF may have pathological significance in AD. In healthy individuals, SWJs are generated by VF and suppressed without VF. Conversely, in AD, SWJs are generated rather than suppressed in the absence of VF. These pathognomonic SWJs without VF also appear to be correlated with higher-order dysfunction, reflecting AD-related cortical damage. These findings suggest that pathological SWJs without VF observed in AD derive from cortical damage and may constitute an important marker of a higher-order function.

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Title Plasma Repressor Element 1-Silencing Transcription Factor Levels Decrease in Patients With Alzheimer's Disease

10.21203/rs.3.rs-215327/v1 ◽

2021 ◽

Author(s):

Mingqing Wei ◽

Jingnian Ni ◽

Jing Shi ◽

Ting Li ◽

Xiaoqing Xu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Medial Temporal Lobe Atrophy ◽

Protein Levels ◽

Significant Difference ◽

Amci Group ◽

Lobe Atrophy ◽

Repressor Element

Abstract Background: Repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST) was considered as a new therapeutic target for neurodegenerative disorders like Alzheimer’s disease (AD). However, the relationships between AD and REST remain unclear. This study aimed to 1) examine plasma REST levels and REST gene AD patients, and 2) further explore the pathological relationships between REST protein levels and cognition decline in clinic, including medial temporal-lobe atrophy. Methods: Subjects (n=252, mean age 68.95±8.78 years old) were recruited in Beijing, China, and then divided into normal cognition (NC) group (n=89), amnestic mild cognitive impairment (aMCI) group (n=79) and AD group (n=84) according to diagnostic criteria. All subjects received neuropsychological assessments, laboratory tests and neuroimaging scans (MRI) at baseline. Plasma REST protein levels and distribution of the single-nucleotide polymorphisms (SNPs) of REST were compared across the three groups. Correlation between cognitive function, neuro-image and REST level was calculated using multi-linear-regression analysis. medial temporal-lobe atrophy (need to add this method). Results: The plasma REST levels in both NC group (430.30±303.43) and aMCI group (414.27±263.39) were significantly higher than AD group ( NC vs AD, p=0.034; aMCI vs AD, p=0.033). There was no significant difference between NC and aMCI group (p=0.948). There was no significant difference among three groups on the distribution of the genotype distribution of Rs2227902 and Rs3976529 of REST gene. The REST level was correlated to left medial temporal-lobe atrophy index (r=0.306, p=0.023). After 6-month follow up, the REST level in NC group was positively related to the change scores of mini-mental state examination scale (MMSE) (r=0.289, p=0.02). Conclusion: Plasma REST protein declines in AD patients, which also associated with memory impairment and left temporal-lobe atrophy, which may have potential value for clinical diagnosis of AD.

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The Association Between Anemia of Chronic Inflammation and Alzheimer’s Disease and Related Dementias

Journal of Alzheimer s Disease Reports ◽

10.3233/adr-200178 ◽

2020 ◽

Vol 4 (1) ◽

pp. 379-391

Author(s):

Alexander Andreev ◽

Burak Erdinc ◽

Kiran Shivaraj ◽

Julia Schmutz ◽

Olga Levochkina ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Chronic Inflammation ◽

Binding Capacity ◽

Control Group ◽

P Value ◽

Iron Level ◽

Retrospective Case ◽

Significant Difference ◽

Anemia Of Chronic Inflammation

Background: Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer’s disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively. Objective: To study an association between ADRD and anemia of chronic inflammation. Methods: We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were performed using a Mann–Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population. Results: There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p-value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2–8.4] and 13% [95% CI: 9.8–16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8–22.1]. Conclusion: We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels.

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Alexithymia in Alzheimer’s Disease

Journal of Clinical Medicine ◽

10.3390/jcm10010044 ◽

2020 ◽

Vol 10 (1) ◽

pp. 44

Author(s):

Eva Mª Arroyo-Anlló ◽

Corinne Souchaud ◽

Pierre Ingrand ◽

Jorge Chamorro Sánchez ◽

Alejandra Melero Ventola ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Abilities ◽

Rating Scale ◽

Mood State ◽

Neuropsychological Test ◽

Control Group ◽

Control Groups ◽

Significant Difference ◽

And Control

Alexithymia is widely recognized as the inability to identify and express emotions. It is a construct which consists of four cognitive traits such as difficulty in identifying feelings, describing feelings to others, externally oriented thinking, and limited imaginative capacity. Several studies have linked alexithymia to cognitive functioning, observing greater alexithymia scores associated with poorer cognitive abilities. Despite Alzheimer’s disease (AD) being a neurodegenerative pathology characterized by cognitive troubles from the early stages, associated to behavioral and emotional disturbances, very few investigations have studied the alexithymia in AD. These studies have shown that alexithymia scores—assessed with Toronto Alexithymia Scale (TAS)—were greater in AD patients than healthy participants. The objective of the study was to investigate if the alexithymia was present in patients with mild AD. We hypothesized that the AD group would show more alexithymia features than the control group. We evaluated 54 subjects, including 27 patients diagnosed with mild AD and 27 normal healthy controls, using the Shalling Sifneos Psychosomatic Scale (SSPS-R) and a neuropsychological test battery. Using non-parametric statistical analyses—Wilcoxon and Mann–Whitney U tests—we observed that the SSPS-R scores were similar in the AD and control groups. All participants showed SSPS-R scores below to 10 points, which means no-alexithymia. We did not find significant correlations between SSPS-R scores and cognitive variables in both groups (p > 0.22), but we observed a negative association between name abilities and alexithymia, but it does not reach to significance (p = 0.07). However, a significant correlation between SSPS-R score and mood state, assessed using Zerssen Rating Scale, was found in both groups (p = 0.01). Because we did not find a significant difference in the alexithymia assessment between both subject groups, pot hoc analyses were computed for each item of the SSPS-R. We made comparisons of alexithymic responses percentages in each SSPS-R item between AD and control groups, using Fisher’s test. We observed that AD patients produced more alexithymic responses in some items of SSPS-R test than the control group, particularly about difficulties to find the words to describe feelings, as well as difficulties of imagination capacity and externally oriented thinking. The present results do not confirm our hypothesis and they do not support the results of previous studies revealing great alexithymia in AD.

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Working memory task performance and chunking in early Alzheimer's disease

The British Journal of Psychiatry ◽

10.1192/bjp.bp.110.083857 ◽

2011 ◽

Vol 198 (5) ◽

pp. 398-403 ◽

Cited By ~ 29

Author(s):

Jonathan Huntley ◽

Daniel Bor ◽

Adam Hampshire ◽

Adrian Owen ◽

Robert Howard

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Working Memory ◽

Spatial Working Memory ◽

Memory Performance ◽

Verbal Working Memory ◽

Control Group ◽

Mild Disease ◽

Significant Difference ◽

Encoding Strategy

BackgroundChunking is a powerful encoding strategy that significantly improves working memory performance in normal young people.AimsTo investigate chunking in patients with mild Alzheimer's disease and in a control group of elderly people without cognitive impairment.MethodPeople with mild Alzheimer's disease (n = 28) were recruited and divided according to Mini-Mental State Examination score into mild and very mild disease groups. A control group of 15 elderly individuals was also recruited. All participants performed digit and spatial working memory tasks requiring either unstructured sequences or structured sequences (which encourage chunking of information) to be recalled.ResultsThe control group and both disease groups performed significantly better on structured trials of the digit working memory tasks, indicating successful use of chunking strategies to improve verbal working memory performance. The control and very mild disease groups also performed significantly better on structured trials of the spatial task, whereas those with mild disease demonstrated no significant difference between the structured and unstructured spatial conditions.ConclusionsThe ability to use chunking as an encoding strategy to improve verbal working memory performance is preserved at the mild stage of Alzheimer's disease, whereas use of chunking to improve spatial working memory is impaired by this stage. Simple training in the use of chunking might be a beneficial therapeutic strategy to prolong working memory functioning in patients at the earliest stage of Alzheimer's disease.

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