Senile Dementia Of The Alzheimer Type Research Articles

Age-related cognitive impairment is associated with low serum concentrations of testosterone and CSF levels of amyloid beta 42 in male cynomolgus monkeys (Macaca fascicularis).

Aged memory-impaired cynomolgus monkeys had significantly lower levels of cerebrospinal amyloid (Aβ42 ) and serum testosterone compared with young animals and non-memory-impaired controls. Our findings confirm similar findings in the human and substantiate the usefulness of the cynomolgus monkey as a spontaneous model for aging-associated senile dementia of the Alzheimer type.

Relationship between blood coagulability and sense of burden among caregivers of patients with dementia.

This study aimed to examine the relationship between blood coagulability and sense of burden among caregivers of patients with senile dementia of the Alzheimer type. A cross-sectional study was carried out involving healthy older caregivers who lived with their patients with senile dementia of the Alzheimer type. We evaluated the Zarit Burden Interview score, levels of von Willebrand factor antigen, D-dimer, thrombin-antithrombin III complex, tissue plasminogen activator/plasminogen activator inhibitor type 1 complex, number of chronic diseases, body mass index and number of medications. A linear regression model was used to estimate adjusted associations. Thrombin-antithrombin III complex levels were higher in female caregivers than in male caregivers (P = 0.07). Headaches were significantly more frequent in female caregivers than in male caregivers, as assessed by a visual analog scale (P < 0.01). The number of chronic diseases and body mass index were positively associated with levels of tissue plasminogen activator/plasminogen activator inhibitor type 1 complex (P < 0.05). Similarly, the number of medications was positively associated with levels of D-dimer (P < 0.05). However, the Zarit Burden Interview score was not associated with blood coagulability (P > 0.05). The present study found that the number of chronic diseases and body mass index were associated with blood coagulability, and that female caregivers were more prone to headaches and higher blood coagulability than male caregivers. These findings highlight the essential nature of health management during caregiving. The impact of caregiver burden on blood coagulability is likely to differ depending on the long-term or short-term psychological stress associated with caregiving conditions. Geriatr Gerontol Int 2019; 19: 804-808.

Evaluation of cognitive impairment in senile dementia of the Alzheimer type

Evaluation of cognitive impairment in senile dementia of the Alzheimer type

Mental Exercises for Cognitive Function: Clinical Evidence

The purpose of this study was to examine the beneficial effects of a new cognitive intervention program designed for the care and prevention of dementia, namely Learning Therapy. The training program used systematized basic problems in arithmetic and Japanese language as training tasks. In study 1, 16 individuals in the experimental group and 16 in the control group were recruited from a nursing home. In both groups, all individuals were clinically diagnosed with senile dementia of the Alzheimer type. In study 2, we performed a single-blind, randomized controlled trial in our cognitive intervention program of 124 community-dwelling seniors. In both studies, the daily training program using reading and arithmetic tasks was carried out approximately 5 days a week, for 15 to 20 minutes a day in the intervention groups. Neuropsychological measures were determined simultaneously in the groups both prior to and after six months of the intervention. The results of our investigations indicate that our cognitive intervention using reading and arithmetic problems demonstrated a transfer effect and they provide convincing evidence that cognitive training maintains and improves the cognitive functions of dementia patients and healthy seniors.

Validity and Reliability of the Persian Language Version of the Neuropsychiatry Unit Cognitive Assessment Tool

Background/Aims: Only a limited number of cognitive screening tools are available for the Persian-speaking population, and we sought to translate and validate the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a multidimensional cognitive screening tool. Methods: We used multiple language specialists to translate and then back-translate the NUCOG, and administered the Persian language NUCOG and Mini-Mental State Examination (MMSE) to 184 individuals: 60 controls and 124 patients, 33 of whom had dementia, 30 non-dementing neurological disorders and 61 a psychiatric illness. Results: The NUCOG outperformed the MMSE in differentiating the patient groups and controls. The ‘profile’ across the 5 NUCOG domains differentiated dementia subgroups such as senile dementia of the Alzheimer type (SDAT), frontotemporal dementia and mild cognitive impairment (MCI). Psychiatric patients with psychosis and posttraumatic stress disorder were more impaired than patients with affective disorders. The NUCOG reliably differentiated controls from patients with MCI (at 86.5/100, sensitivity of 83.3% and specificity of 87.5%) and SDAT (at 75/100, sensitivity and specificity of 100%) patients from controls. Conclusions: The Persian language NUCOG appears to perform strongly in an unselected population, reliably differentiating patients with dementia from controls, and detecting cognitive impairment in a range of clinical disorders.

Alzheimer's disease in family practice

Abstract21 September 2009 is hailed as World Alzheimer's Day, creating awareness for the most common type of all the dementias. Senile dementia of the Alzheimer's type (SDAT) has a four to five year survival rate if a patient is living in the community and a much shorter survival rate for institutionalised patients. The family practitioner is often consulted first by family members who seek advice for a family member with suspected dementia and possibly Alzheimer's disease. Although a multi-disciplinary team approach is mostly needed, the family practitioner will in most cases co-ordinate referrals and advise family members on practical nursing aspects and decisions about institutionalisation. This article gives a short overview on SDAT, a classification of drugs used in dementia and a treatment approach to Alzheimer-specific pharmacotherapy.

Quantitative EEG in patients with presenile and senile dementia of the Alzheimer type

EEG data obtained from 27 patients with presenile Alzheimer's disease (AD) and 28 patients with senile dementia of the Alzheimer type (SDAT) were compared with data from 30 age- and sex-matched controls. Both patient groups exhibited more pronounced delta and theta activity and less prominent alpha and beta activity than the controls. AD, however, was accompanied by more severe slowing than SDAT. The slowing was distributed in the left temporal and frontal regions in AD, and bilaterally in the frontal regions in SDAT. As the severity of the dementia increased, delta activity alone increased in AD, whereas, there were significantly greater increases in both delta and theta activity and decreases in alpha and beta activity in SDAT. These EEG differences appear to be related to the degree of brain damage and the speed of progression of the disease process.

Alzheimer's disease: maintenance of neuronal and synaptic densities in frontal cortical layers II and III.

Neuronal loss and alterations of the cortical neuropil were previously described on necropsic material from patients with senile dementia of the Alzheimer type, and the results compared to age-matched case controls. In frontal cortex biopsic material from our patients with Alzheimer's disease, the numerical densities of neurons and synapses were not significantly different from controls, indicating that changes in the highest cognitive functions might not depend on a generalized loss of neurons and synapses and that quantitative morphological differences may exist between Alzheimer's disease and senile dementia of the Alzheimer type.

Serum lipoprotein pattern variations in dementia and ischemic stroke

Blood levels of triglycerides, total cholesterol, isolated lipoprotein fractions (VLDL-LDL- and HDL-cholesterol) and apoproteins (Apo-A1 and Apo-B) were examined in multi-infarct dementia, senile dementia of the Alzheimer type, ischemic stroke associated with carotid atherosclerosis and in control subjects. Forty patients divided into 10 consecutive patients for each group were studied. Alzheimer patients showed mean total cholesterol and Apo-B values significantly higher than control subjects. Apo-B was significantly higher in stroke patients than in controls. The mean lowest HDL-cholesterol (HDL-c) value was observed in stroke patients. No significant differences in mean HDL-c levels were found between patients with multi-infarct and Alzheimer dementia.

P2.059 A proposed environment to promote unrestricted wandering in people who have senile dementia of the Alzheimer type

P2.059 A proposed environment to promote unrestricted wandering in people who have senile dementia of the Alzheimer type

Pathogenesis of amyloid formation in Alzheimer's disease, Down's syndrome and scrapie.

Paired helical filaments (PHF) are abnormal fibrous structures found in human nerve cells and their processes. Ultrastructural studies of the proto-filaments that make up the PHF revealed that the individual proto-filaments have a different substructure from normal neurofilaments or any other known fibrous profiles. Studies using immunological and biochemical methods suggested that abnormally phosphorylated tau, ubiquitin and neurofilament peptides are part of the PHF. Deposits of amyloid fibres in Alzheimer's disease and senile dementia of the Alzheimer type (AD/SDAT) are found in meningeal and brain vessels, choroid plexus and neuritic plaques. In 1984 Glenner and Wong reported the sequence of a beta-protein isolated from cerebrovascular amyloid. We used the amino acid sequence of the cerebrovascular amyloid protein to synthesize oligonucleotide probes specific for the gene encoding this amyloid protein. Screening of a human brain cDNA library allowed us to isolate a clone which encodes the amyloid peptide. In situ hybridization studies and Southern blot analysis of a DNA sample isolated from a human-mouse hybrid cell line indicated that the corresponding genomic sequences of this cDNA clone are located on human chromosome 21. Using immunochemical and histochemical methods, we have identified the cells associated with the formation of the amyloid fibres. With immunochemical and biochemical methods we and others also showed that the protein constituting amyloid in AD/SDAT is different from amyloid in unconventional slow virus diseases.

Prenatal exposure to the acetylcholinesterase inhibitor methanesulfonyl fluoride alters forebrain morphology and gene expression

Methanesulfonyl fluoride (MSF) is a CNS-selective acetylcholinesterase (AChE) inhibitor, currently being developed and tested for the treatment of symptoms of Alzheimer's disease [D.E. Moss, P. Berlanga, M.M. Hagan, H. Sandoval, and C. Ishida, Methanesulfonyl fluoride (MSF): a double-blind, placebo-controlled study of safety and efficacy in the treatment of senile dementia of the Alzheimer type, Alzheimer Dis. Assoc. Disord., 13 (1999) 20–25] [43]. We have previously confirmed that a single in utero exposure to MSF at clinically appropriate doses inhibits AChE activity in fetal rat brain by 20%, and when administered throughout gestation, MSF achieves a 40% level of inhibition. Here, we show that rats chronically exposed in utero to MSF display marked sex-specific differences in morphological development of the cerebral cortical layers compared with controls at 7 days of age. Forebrain size and cortical thickness were increased in females and decreased in males. An analysis of gene expression in neonate brain on the day of birth revealed sex-specific differential expression of over 25 genes, including choline acetyltransferase (ChAT), which were affected by prenatal MSF exposure. Many of these genes are associated with sexual differentiation and brain development, while others are involved in more generalized cellular and metabolic processes. The changes observed in cortical morphology and gene expression suggest a critical developmental role for AChE in the fetal nervous system, most likely through its effect on cholinergic neurotransmission.

EEG Mapping and Low-Resolution Brain Electromagnetic Tomography (LORETA) in Diagnosis and Therapy of Psychiatric Disorders: Evidence for a Key-Lock Principle

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.

Severe cognitive impairment correlates with higher cerebrospinal fluid levels of lactate and pyruvate in a canine model of senile dementia

Diagnosis of dementia of the Alzheimer's type depends on clinical criteria and exclusion of other disorders because, at this time, a validated biological marker, aside from histological brain examination, remains to be established. The canine counterpart of senile dementia of the Alzheimer type (ccSDAT) is considered a promising model for examining behavioral, cellular and molecular processes involved in early phases of human brain aging and Alzheimer disease (AD). In order to investigate the first events taking place in canine cognitive dysfunction, in this paper we established a new and rapid behavioral test that finely discriminates the degrees of cognitive impairment. Cerebrospinal fluid (CSF) analysis was performed to determine the relationship between each disease stage and modification of cerebral energy metabolism. Our results demonstrate a parallel increase of lactate, pyruvate and potassium concentrations in the severe cognitive deficit. These differences are discussed in view of the neuroprotective role presently given to lactate.

Protein folding pathology in domestic animals.

Fibrillar proteins form structural elements of cells and the extracellular matrix. Pathological lesions of fibrillar microanatomical structures, or secondary fibrillar changes in globular proteins are well known. A special group concerns histologically amorphous deposits, amyloid. The major characteristics of amyloid are: apple green birefringence after Congo red staining of histological sections, and non-branching 7-10 nm thick fibrils on electron microscopy revealing a high content of cross beta pleated sheets. About 25 different types of amyloid have been characterised. In animals, AA-amyloid is the most frequent type. Other types of amyloid in animals represent: AIAPP (in cats), AApoAI, AApoAII, localised AL-amyloid, amyloid in odontogenic or mammary tumors and amyloid in the brain. In old dogs Abeta and in sheep APrPsc-amyloid can be encountered. AA-amyloidosis is a systemic disorder with a precursor in blood, acute phase serum amyloid A (SAA). In chronic inflammatory processes AA-amyloid can be deposited. A rapid crystallization of SAA to amyloid fibrils on small beta-sheeted fragments, the 'amyloid enhancing factor' (AEF), is known and the AEF has been shown to penetrate the enteric barrier. Amyloid fibrils can aggregate from various precursor proteins in vitro in particular at acidic pH and when proteolytic fragments are formed. Molecular chaperones influence this process. Tissue data point to amyloid fibrillogenesis in lysosomes and near cell surfaces. A comparison can be made of the fibrillogenesis in prion diseases and in enhanced AA-amyloidosis. In the reactive form, acute phase SAA is the supply of the precursor protein, whereas in the prion diseases, cell membrane proteins form a structural source. Abeta-amyloid in brain tissue of aged dogs showing signs of dementia forms a canine counterpart of senile dementia of the Alzheimer type (ccSDAT) in man. Misfolded proteins remain potential food hazards. Developments concerning prevention of amyloidogenesis and therapy of amyloid deposits are shortly commented.

The role of free radicals in canine counterpart of senile dementia of the Alzheimer type

The pathogenesis of Alzheimer's disease is still unknown. In recent time oxidative stress has been discussed as an important contributor. In the present study we investigated the role of free radicals in the spontaneous canine model of Alzheimer's disease. We analysed end-products of lipid peroxidation: lipofuscin-like pigments (LFP), protein carbonyls, and vitamin E to obtain data on oxidative damage in brain of demented dogs. When the generation of free radicals is intensive the toxic products of lipid peroxidation can diffuse from the site of the primary formation and merge with erythrocytes. Therefore we also determined the level of lipid peroxidation in red blood cells. In brain of demented animals the level of LFP increased (to 247%, P<0.05) as well as of protein carbonyls (to 438%, P<0.01) while the vitamin E concentration was lowered (to 34%, P<0.01) when compared to age-matched non-demented controls. The end-products of lipid peroxidation have been found increased also in erythrocytes of demented dogs (250%, P<0.05). These results indicate intensive production of free radicals in brain of animals with dementia which induces damage to erythrocytes. Detection of the specific products of free radical damage in blood samples could be used for diagnostic purposes.

Canine counterpart of senile dementia of the Alzheimer type: amyloid plaques near capillaries but lack of spatial relationship with activated microglia and macrophages

Senile plaques and cerebrovascular amyloidosis are major histopathological lesions in the brains of aged dogs. Different types of amyloid beta protein (Aβ) positive plaques are known: diffuse ones and neuritic plaques. Diffuse plaques may contain membrane-bound Aβ and/or small amounts of amyloid fibrils. Neuritic plaques are cored plaques with clusters of amyloid fibrils and degenerating neurites. In human amyloid plaques, a pathogenetic role for mcroglia cells has been described. The aim of this investigation was to study microglia cells in relationship to canine plaques and to investigate the localisation of amyloid plaques in relationship to vasculature. The lesions were studied by hematoxylin and eosin Congo red staining and immunohistochemistry with anti-Aβ for plaques, with Mac 387, anti lysozyme and a series of lectins for mononuclear cells, with anti von Willebrand Factor and Lycopersicon esculentum (tomato) lectin for the endothelium of brain capillaries.Diffuse Aβ-positive plaques were found in dogs of 10.8 years and older, and cored Appositive plaques with birefringent amyloid in Congo red-stained sections in subjects of 15 years and older. Accumulation of microglia cells in relationship to the plaques was not obvious. With anti Aβ8–17 the distribution of the plaques in the cortical layers varied. The younger dogs had primarily diffuse plaques in the deeper layers of the cortical grey matter. The older dogs showed more cored plaques than diffuse plaques which were found throughout all cortical grey matter layers. With anti Aβx-42 more plaques were found positive, especially diffuse ones, whereas staining results of anti Aβx-40 were more confined to amyloid plaques and vascular amyloid. A close spatial relationship was found between the cored plaques and capillaries.

Partial cross-validation of the Wechsler Memory Scale—Revised (WMS-R) General Memory—Attention/Concentration Malingering Index in a nonlitigating sample

The Wechsler Memory Scale—Revised (WMS-R) malingering indices proposed by Mittenberg, Azrin, Millsaps, and Heilbronner [Psychol Assess 5 (1993) 34.] were partially cross-validated in a sample of 200 nonlitigants. Nine diagnostic categories were examined, including participants with traumatic brain injury (TBI), brain tumor, stroke/vascular, senile dementia of the Alzheimer’s type (SDAT), epilepsy, depression/anxiety, medical problems, and no diagnosis. Results showed that the discriminant function using WMS-R subtests misclassified only 6.5% of the sample as malingering, with significantly higher misclassification rates of SDAT and stroke/vascular groups. The General Memory Index—Attention/Concentration Index (GMI-ACI) difference score misclassified only 8.5% of the sample as malingering when a difference score of greater than 25 points was used as the cutoff criterion. No diagnostic group was significantly more likely to be misclassified. Results support the utility of the GMI-ACI difference score, as well as the WMS-R subtest discriminant function score, in detecting malingering.

Clinical significance of white matter changes in senile dementia of the Alzheimer type.

Clinical significance of white matter changes in senile dementia of the Alzheimer type.

Synapse loss is greater in presenile than senile onset Alzheimer disease: implications for the cognitive reserve hypothesis

In the past, 'Alzheimer disease' (AD) referred to pathologic AD with clinical onset of dementia in the presenium, while 'senile dementia of the Alzheimer type' (SDAT) referred to senile onset AD. Because AD appears clinically homogeneous regardless of age of onset, the two subtypes in more recent years have not been distinguished. Pathologic differences have been noted, but synapse loss has not previously been compared between the two groups. Hypothesizing that synapse loss would be greater in presenile onset than senile onset AD, we compared synapse loss, as well as Alzheimer pathology in presenile and senile onset AD, using an ELISA method to quantify synaptophysin. Synaptophysin was significantly lower in presenile than senile AD in right frontal and bilateral parietal lobes. Neuritic plaque counts were significantly higher in presenile than senile AD in bilateral frontal and parietal lobes. Semi-quantitative evaluation of neurofibrillary tangles revealed significantly more tangles in bilateral frontal and parietal lobes in presenile than senile AD. Brain weight was significantly lower in presenile than senile AD. The differences in synapse loss and Alzheimer-type pathology in presenile and senile onset AD support the hypothesis that 'cognitive reserve' protects the human brain from neurodegenerative disease.