Significant Cognitive Loss Research Articles

Low-dose anticholinergic therapy causes cognitive impairment in Parkinson's disease patients

Background: Before L-Dopa’s discovery, anticholinergic drugs were among the first treatments for Parkinson’s disease. Only now trihexyphenidyl (THP) is approved to treat unresponsive L-dopa tremors in young, cognitively unaffected Parkinson’s disease patients. However, there are no specific recommendations for disease duration, medication dose, or cognitive status. In low-income countries, THP is still frequently used in Parkinson’s disease patients with tremor. The objective of the current study was to evaluate cognitive performance in Parkinson’s disease patients receiving a low dose of THP. Material and methods: The study was performed on nineteen PD patients, nine of whom were on THP. All patients completed MoCA cognitive assessment. The patients were matched depending on their age, disease severity based on UPDRS III and duration of the disease. Results: The THP patients were taking an average dose of 3.3 mg of THP daily for an average of 1.8 years. There were no statistical differences between THP patients and non-THP patients in age (64.8± 4.8 vs 67.2±6.9, p=0.4), UPDRS III (32.1±8.9 vs 41.5±20.6, p=0.2) and disease duration (6.2±4.9 vs 7.0 ± 4.0, p=0.7). The THP patients had lower cognitive performance, with a total MoCA of 19.22 ± 3.3 vs. non-THP patients 24.2±3.0, p=0.003. Conclusions: In Parkinson’s disease patients, even a low dose of THP causes significant cognitive loss.

The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia with a growing incidence rate primarily among the elderly. It is a neurodegenerative, progressive disorder leading to significant cognitive loss. Despite numerous pieces of research, no cure for halting the disease has been discovered yet. Phytoestrogens are nonestradiol compounds classified as one of the endocrine-disrupting chemicals (EDCs), meaning that they can potentially disrupt hormonal balance and result in developmental and reproductive abnormalities. Importantly, phytoestrogens are structurally, chemically, and functionally akin to estrogens, which undoubtedly has the potential to be detrimental to the organism. What is intriguing, although classified as EDCs, phytoestrogens seem to have a beneficial influence on Alzheimer's disease symptoms and neuropathologies. They have been observed to act as antioxidants, improve visual-spatial memory, lower amyloid-beta production, and increase the growth, survival, and plasticity of brain cells. This review article is aimed at contributing to the collective understanding of the role of phytoestrogens in the prevention and treatment of Alzheimer's disease. Importantly, it underlines the fact that despite being EDCs, phytoestrogens and their use can be beneficial in the prevention of Alzheimer's disease.

Effect of N-Acetyl Cysteine on Intracerebroventricular Colchicine Induced Cognitive Deficits, Beta Amyloid Pathology, and Glial Cells.

Among the many factors responsible for the cognitive decline in Alzheimer's disease, beta amyloid protein and plaque formation is crucial. This amyloid pathology is associated with activation of glial cells and oxidative stress but whether oxidative stress activates beta amyloid protein in the neurons is not clear. Further the expression of microglia is also known to vary during pathogenesis of beta amyloid plaques. The aim of the present study is to evaluate the antioxidant effect of NAC on amyloid pathology and cognition and also to investigate the link between amyloid pathology and glial cells activation. Intracerebroventricular colchicine in rats known mimics human AD in many aspects including memory loss, oxidative stress, and hyper phosphorylation of tau protein. The animal groups consisted of age matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in active avoidance test; beta amyloid protein, beta amyloid plaques, astrocytes, and microglia cells were quantified using immunohistochemistry in hippocampal and prefrontal cortices. Colchicine has resulted in significant cognitive loss, increased intraneuronal beta amyloid protein expression, increased reactive astrocytes, and activated microglia in all the regions of the hippocampus and prefrontal cortices. The antioxidant NAC has reversed the cognitive deficits and inhibited microglia activation but failed to inhibit BAP expression and astrocytosis. Intraneuronal BAP accumulation is deleterious and known to adversely affect cognition, but in this study in spite of intraneuronal BAP accumulation, the cognition is restored. It can be postulated that NAC might have reversed the effect of intraneuronal beta amyloid protein by acting on some downstream compensatory mechanisms which needs to be explored.

C-PLACID - Computational PLatform for Assessment of Cognition In Dementia - EPSRC

C-PLACID - Computational PLatform for Assessment of Cognition In Dementia - EPSRC

Nimodipine activates neuroprotective signaling events and inactivates autophages in the VCID rat hippocampus

Background: Autophagy and phosphatidylinositol 3-kinase (PI3K)/Akt kinase pathways are implicated in cognitive decline associated with cerebrovascular lesions. This decline is reflected in the concept of vascular cognitive impairment and dementia (VCID). However, the underlying molecular mechanism and specific details regarding these types of cognitive deficits induced by chronic brain hypoperfusion have not been elucidated.Methods: We designed a method to evaluate these mechanisms. Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid artery (2VO) and randomly divided into three groups: Sham, Vehicle (2VO), and Nimodipine10 (2VO + nimodipine 10 mg/kg). Each group was studied for 4 weeks postoperatively and assessed by the Morris water maze.Results: The results of this study show that chronic brain hypoperfusion significantly increased the number of autophagic vacuoles with high LC3 II levels, but it decreased p-Akt and p-CREB levels, which were involved in the PI3K/Akt kinase pathway in the hippocampi of rats. Additionally, significant cognitive losses were observed following 2VO. Further analysis showed that, in VCID rats subjected to 2VO, nimodipine administration decreased autophagy, increased the Akt/CREB signaling pathway and significantly reduced brain damage.Conclusions: We concluded that neuronal pathology and activation of the autophagic and Akt/CREB signaling pathway caused by chronic brain hypoperfusion could suppress cognitive behavior, which may provide a novel way for the prevention of VCID. The results of this study indicate that nimodipine protected the brain from chronic brain hypoperfusion damage by suppressing autophagy and activating the Akt/CREB signaling pathway.

Forensic neuropsychological assessment: clinical case of depression and working incapacity

Issues related to mental health in relation to court matters have increasingly required the participation of the psychologist. We present the use of forensic neuropsychological assessment in a case of retirement reversal. Incapacity was attested due to disability resulting from depression of a 35-year-old attorney, and the case was forwarded from the courts to the Forensic Psychiatry and Psychology Unit at the USP Clinical Hospital. A clinical interview and application of cognitive tests was conducted. Despite the depression, significant cognitive losses that would prevent return to his professional assignments were not detected. The neuropsychological assessment has been shown to be an important tool in the forensic context, as it assists with diagnostic value for clarification of functional aspects in the various psychopathological areas in terms of disabilities or potentialities.

The effects of high- and low-risk environments on cognitive function in rats following 2-vessel occlusion of the carotid arteries: A behavioral study

In a prospective study of environmental factors affecting cognitive recovery from stroke, adult male rats were reared for 3 months in a high-risk (relatively isolated, low activity, high-fat diet, high-stress) or low-risk (social, healthy diet, low-stress, physically active) environment. They then received cognitive testing to assess various aspects of learning and memory before undergoing 2-vessel occlusion (2VO) of the carotid arteries, or sham surgery. Rats were returned to their respective environments post-operatively. Relative to pre-operative levels, 2VO rats exhibited significant cognitive losses that were consistently greater in the high-risk group than its low-risk counterpart. As well, the high-risk 2VO group was impaired, relative to the low-risk 2VO group on tests of new learning introduced post-operatively. At 3-month follow-up testing, rats that had undergone 2VO surgery exhibited further decline on some tests but recovery on others, with recovery generally slower in the high-risk 2VO group. The high-risk environment also affected rats’ pre-operative cognitive performance and, to a lesser extent, their performance following sham surgery. Overall, the study shows that rats experiencing cerebral ischemia are more likely to experience severe cognitive deficits if exposed to a high-risk environment and recover more slowly than ischemic rats in a more favorable environment. The results underscore the importance of lifestyle factors with respect to the impact of stroke on cognition and in assessing prospects for recovery of function.

Clinical Utility of Reliable Digit Span in Assessing Effort in Children and Adolescents with Epilepsy

The assessment of effort is an important aspect of a comprehensive neuropsychological evaluation, as this can significantly impact data interpretation. While recent work has validated the appropriateness of adult-derived cutoffs for standalone effort measures in younger populations, little research has focused on embedded effort measures in children. The present study includes 54 clinically referred children and adolescents (32 males/22 females; aged 6-17) with a confirmed diagnosis of epilepsy. Reliable Digit Spans (RDSs) were calculated and the Test of Memory Malingering (TOMM) was administered in the context of a comprehensive neuropsychological evaluation. Using a previously published RDS cutoff of ≤6, a pass rate of only 65% was obtained, well below the recommended 90% pass rate for an effective effort index. In contrast, when adult criteria were used on TOMM Trial 2, a 90% pass rate was observed. RDS scores were significantly correlated with IQ estimates (r = .59, p < .001) and age (r = .61, p < .001). The difference between RDS and the TOMM on the participant outcome was statistically significant (χ(2) = 9.05, p = .003). These results suggest that RDS appears to yield a large number of false positives and, therefore, may be of limited utility in detecting poor effort in a pediatric epilepsy population. These findings likely extend to other pediatric populations that are known to have significant cognitive loss.

P146 Cognitive loss in stable non-hypoxaemic patients with moderate chronic obstructive pulmonary disease (COPD)

BackgroundCognitive impairment has been demonstrated in up to 77% of patients with COPD and hypoxaemia,1 however it is unclear if this impairment is due to cognitive loss or was present...

Alzheimer's Disease is Incurable but Preventable

The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment.

A correlation of haloperidol-induced cognitive deficit with dysfunctional dopamine receptor activity in nonhuman primate

Haloperidol is an antipsychotic drug that acts through blockage of dopamine D 2 receptors. Chronic administration of this antipsychotic drug in nonhuman primates induces a pronounced cognitive deficit. However, receptor subtypes that are responsible for this cogni - tive dysfunction remain unknown. Therefore, brains of chronic haloperidol-treated young and aged monkeys were used to analyze the intricate relation of receptor activity, cognitive dysfunction, and haloperidol-mediated actions in the production of harmful effects. Tak- ing into account the significant cognitive loss observed after haloperidol treatment, it was predicted that changes in the cognitive status that correlate with the receptor activity in the prefrontal cortex and striatum, areas implicated in the processing of haloperidol-mediated effects in brain, should be common in both young and aged animals. Based on this concept, we observed that in the prefrontal cortex, dopamine D 1 and D 2 receptors showed changes in receptor levels that were common in both age groups. However, this relationship was absent in GABA A , serotonin 5HT2 and muscaranic receptors. In contrast to the prefrontal cortex, in striatum, this change was restricted to the dopamine D 2 receptors only. Therefore, from our results, it seems that apart from the downregulation of D 1 receptor activity in the prefrontal cortex, an upregulation of D 2 receptors could also contribute to the generation of the cognitive loss observed in haloperidol-treated monkeys. Additionally, reduced excitatory input due to hampered cortico-striatal D 1 dopaminergic activity and stronger inhibition at the synapse of excitatory input site by upregulated striatal D 2 receptor activity could promote the side effects

Cognitive status and the psychological well-being of long-term care residents over time

The majority of research within long-term care (LTC) has emphasized the physical health of residents, has been cross-sectional in design and has focused almost exclusively on residents with dementia. Few longitudinal studies have followed participants over intervals longer than 1 year. In contrast, the current study set out to examine the experience of LTC residents with and without significant cognitive loss over a 2-year period comparing the psychological well-being of groups over time. Significant Group × Time interaction effects were observed between residents with and without significant cognitive loss in life satisfaction and depressive symptomatology. Results of this study underscore the need for longitudinal measurement in LTC research, the use of multivariate statistical procedures and the need to identify and meet the distinct needs of residents with and without significant cognitive loss.

Chapter 29 Neuropathological changes in Alzheimer disease

Alzheimer's disease (AD) is principally a disorder of the elderly, its pathology is additive to that of normal aging. Therefore, neuron loss is less in the old Alzheimer's patients than it is in the younger ones. Similarly, the concentration of plaques and tangles in the older AD patients is less than in the younger ones. One might infer from these findings that there is a threshold of brain damage which must be reached in order that the patient display significant cognitive loss. Older patients need less additional pathology to reach this threshold than do younger individuals. A greater reserve of neurons and synapses is probably protective. The classical, diagnostic lesions of AD—the plaque and tangle—do not account satisfactorily for the clinical symptoms of global dementia. Other recently found factors are clearly of great significance. The neuronal and synaptic loss may well be related to abnormalities of the plasma membrane, and thus gangliosides and phospholipids are strongly implicated.