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PubMed2005

Nutritional factors, cognitive decline, and dementia.

Nutritional factors and nutritional deficiencies have been repeatedly associated with cognitive impairment. Most of the evidence is based on cross-sectional studies, which cannot prove whether a nutritional deficit is the cause or the consequence of an impaired cognitive status. In fact, cognitive impairment, in turn, can determine changes in dietary habits and consequent nutritional deficiencies. We reviewed clinical and epidemiological studies from January 1983 to June 2004. Several cross-sectional and fewer prospective studies reported an association between dietary or supplemental intake of antioxidants and protection from cognitive decline and dementia. There are negative reports as well and some methodological biases might have affected the consistencies across studies. Deficiencies of several B vitamins have been associated with cognitive dysfunction in many observational studies. More recently, deficiencies of folate (B9) and cobalamine (B12) have been studied in relation to hyperhomocysteinemia as potential determinants of cognitive impairment, dementia, and Alzheimer's disease (AD). A small number of studies assessed the association between intake of macronutrients and cognitive function or dementia. Among the others, the intake of fatty acids and cholesterol has received particular attention. Although the results are not always consistent, most studies have reported a protective role of dietary intakes of poly- and mono-unsaturated fatty acids against cognitive decline and AD. We point out that well designed intervention studies are warranted in order to establish specific levels of micro- and macronutrient deficiencies and to set general recommendations for the population.

Cognition↗

PubMed2006

Heart failure in elderly patients.

Several structural and functional changes contribute to heart failure in elderly patients: an age dependent increase in sympathetic nervous activity, left ventricular wall diameter, myocardial fibrosis and apoptosis, micro- and macrovascular coronary sclerosis, aortic stiffness. As a consequence, diastolic, but also systolic heart failure is a frequent finding in elderly patients. The relation of systolic to diastolic heart failure is clearly shifted towards diastolic heart failure in elderly patients, especially in women. Mortality is increased with systolic dysfunction in elderly patients compared to younger heart failure patients. Mortality is less with diastolic dysfunction, but still higher compared to elderly without heart failure. In addition, morbidity is increased both with diastolic and systolic heart failure in elderly patients. Cognitive dysfunction is a frequent finding. After exclusion of specific cardiac and extracardiac reasons for dyspnoea, drug therapy of systolic heart failure in elderly is similar to younger patients. However, the physiological decrease of renal function and the more frequent renal impairment in elderly patients with heart failure needs to be considered. Guideline recommendations for drug therapy are based in most cases on studies conducted in younger systolic heart failure patients. A recent meta-analysis of randomized beta-blocker trials suggests improved survival with beta-blockers even in the elderly subgroup. Guidelines for the treatment of diastolic heart failure are available only recently. The term heart failure with normal left ventricular ejection fraction (LVEF) has been proposed instead of diastolic heart failure. Given the increased morbidity and mortality in elderly patients with heart failure and normal LVEF, therapy should include general measures, such as physical activity, weight reduction, volume restriction. Specific therapy includes optimal control of systolic and diastolic blood pressure, diuretics, nitrates, and frequency-control. However, randomized trials evaluating the efficacy of specific therapies in heart failure with normal LVEF are still missing.

Adrenergic beta-Antagonists↗

PubMed2000

Does depression predict cognitive outcome 9 to 12 years later? Evidence from a prospective study of elderly hypertensives.

BACKGROUND: Previous longitudinal studies of the association between depression and cognitive dysfunction have had relatively short follow-up periods. This report presents a long-term study of the association between baseline syndromal depression and cognitive outcome measured 9 to 12 years later. METHODS: Self-CARE (D) depression, cognitive function and pre-morbid intelligence were recorded on 1083 subjects on entry to the Medical Research Council trial of treatment of hypertension in older adults in 1983-5. In 1994-5, we aimed to re-interview all survivors to assess cognitive function using the MMSE. We used multivariate analysis to explore whether baseline depression predicted cognitive outcome after this long follow-up period. RESULTS: Baseline depression was crudely associated with poorer cognitive outcome at time 2. However, this long-term prospective association was no longer apparent after adjusting for baseline cognitive performance, which was associated with baseline depression and robustly predicted cognitive outcome at time 2. We found that gender modified the association between depression and poorer cognitive outcome, so that the association was statistically significant only among men. CONCLUSION: Propensity for depression and failing cognition may have common determinants that still need to be established by future neurobiological investigations in conjunction with further long-term prospective epidemiological research.

Aged↗

PubMed1999

Plasma and cerebrospinal fluid human immunodeficiency virus type-1 (HIV-1) RNA levels in HIV-related cognitive impairment.

Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.

AIDS Dementia Complex↗

PubMed1995

Neuropsychology of multiple sclerosis.

Neuropsychological investigations have demonstrated that cognitive disorders are common (45-65%) in patients with multiple sclerosis. This review summarizes our current understanding of the nature and etiology of these disorders. Specifically, neuropsychological deficits regularly occur on measures of recent memory, attention, information-processing speed, executive functions, and visuospatial perception. In contrast, general intelligence, language, and certain aspects of memory (short-term capacity and implicit) are preserved. The degree and pattern of cognitive dysfunction is highly correlated with the amount and location of white-matter disease within the cerebral hemispheres. Natural history studies indicate that changes in cognitive test performance are correlated with increasing lesion load on magnetic resonance imaging. The development of brief cognitive-testing instruments for clinical screening and measuring treatment effects in clinical trials is underway. A clear weakness in the literature is the dearth of studies evaluating potential treatments for cognitive disorders.

Brain↗

PubMed2006

Alzheimer's disease: psychopathology, medical management and dental implications.

BACKGROUND: The authors review the clinical features, epidemiology, pathophysiology, medical management, dental findings and dental treatment of patients with Alzheimer's disease (AD). STUDIES REVIEWED: The authors conducted MEDLINE searches for 2000 through 2005 using the terms "Alzheimer's disease," "geriatric," "epidemiology," "pathophysiology," "treatment" and "dentistry." Reports selected for further review included those published in English in peer-reviewed journals. The authors gave preference to articles reporting randomized, controlled trials. RESULTS: AD is a progressive and fatal neurodegenerative disorder characterized by cognitive dysfunctions, particularly in learning and memory, and the emergence of behavioral abnormalities. Deficiencies in the cells responsible for storage and processing of information underlie the cognitive, functional and behavioral changes seen in patients with the disorder. CLINICAL IMPLICATIONS: As the elderly population grows, increasing numbers of Americans with AD will require dental treatment. The prevalence of dental disease likely will be extensive, because of diminished salivary flow and patients' inability to perform appropriate oral hygiene techniques. Preventive dental education for the caregiver and use of saliva substitutes and anticaries agents by the patient are indicated.

Age of Onset↗

PubMed2005

Homocysteine in relation to cognitive performance in pathological and non-pathological conditions.

Elevated serum homocysteine has been associated with increased risk of Alzheimer's disease. Furthermore, elevated homocysteine levels are related to cognitive dysfunction in the elderly. The aim of the present study was to explore the disease specificity of the relation between serum total homocysteine levels and cognitive function. For this, we summarize data from several studies on homocysteine levels in both normal and pathological conditions performed in our laboratories and evaluate possible mechanisms of effects of elevated homocysteine levels in the central nervous system. Total homocysteine levels were measured in serum of: 1) healthy aging individuals; 2) patients with Alzheimer's and Parkinson's disease and patients with other cognitive disorders; and 3) patients with multiple sclerosis. Increased serum homocysteine concentration was related to worse cognitive performance over a 6-year period in the normal aging population (r=-0.36 to -0.14, p<0.01 for the Word learning tests; r=0.76, p<0.05 for the Stroop Colored Word test). Homocysteine was only increased in patients with Parkinson's disease on L-Dopa therapy (18.9 vs. 16.5 micromol/L in healthy controls), and not in dementia patients. Homocysteine was elevated in patients with progressive multiple sclerosis (15.0 micromol/L, n=39, compared to 12.0 micromol/L in 45 controls) and correlated to both cognitive and motor function (r=-0.33 and -0.33, p<0.05, respectively). The relationship between homocysteine and cognitive function in non-pathological and pathological situations indicates that changes in its levels may play a role in cognitive functioning in a broad spectrum of conditions.

Animals↗

PubMed2003

[Neuro-immune interactions in psychopathology with the example of interferon-alpha-induced depression].

The use of interferon (IFN)-alpha for the treatment of viral diseases or cancers is associated with neuropsychiatric side effects in a large number of patients. The mechanisms by which cytokines induce these symptoms, as well as the vulnerability factors for these effects, have not been yet fully elucidated. Systematic clinical studies, combining biochemical approaches, functional brain imaging and treatment intervention, have been initiated to better understand the phenomenology, pathophysiology, and preventive strategies of the neuropsychiatric effects of IFN-alpha in patients with malignant melanoma or chronic hepatitis C. The findings indicate differential phenomenology and treatment responsiveness of the neurovegetative and mood/cognitive symptoms induced by IFN-alpha, suggesting distinct underlying mechanisms. Impaired neuroendocine function, fronto-striatal dysfunction and decreased monoamine were found to contribute to the pathophysiology of core symptoms of IFN-alpha-induced depression, including symptoms of mood alterations, cognitive dysfunction, anhedonia and psychomotor retardation. In addition, some behavioral and biological markers of the vulnerability for IFN-alpha-induced depression were identified. These findings provide important information concerning the relationship between cytokines and depression.

Depression↗

PubMed1994

Epilepsy and mental decline.

Experience with prolonged seizures in animal models and humans teaches that cellular injury and cognitive impairment can occur in epilepsy. Status epilepticus probably causes cerebral injury and cognitive dysfunction if it is of long duration; however, studies of electroconvulsive therapy do not support the idea that repeated seizures alone produce a decline in cognitive function. Although many factors related to seizures may correlate with cognitive impairment in certain groups of patients with epilepsy, prospective studies do not support the premise that cognitive impairment develops or progresses in a population of epilepsy patients. When impairment is present, its origin appears to be multifactorial. In addition to the seizures and associated seizure variables (including anticonvulsant medications), interictal epileptiform discharges and the perceptions of the patients and others also may play major roles.

Cognition Disorders↗

PubMed2003

Verbal memory impairment in congestive heart failure.

Cognitive dysfunction, mainly memory impairment, characterizes congestive heart failure (CHF). Aim of this study was to verify whether: (1) CHF has differential effects on primary and secondary memory; (2) memory dysfunction can be diagnosed by a screening instrument. In a multicenter study we enrolled 369 patients with stable CHF who underwent a structured assessment of verbal memory mechanisms and selected cognitive functions. Performance on some verbal memory indexes (Recency, Rey's immediate and delayed recall, Learning efficiency) progressively decreased from II to IV New York Heart Association (NYHA) class. Rate of forgetting was uniformly high across NYHA classes II-IV. Verbal memory indexes were highly correlated with most nonverbal scores. The Mini Mental State Examination (MMSE) had poor sensitivity and specificity versus primary or secondary verbal memory dysfunction. Therefore, a deficit of both primary and secondary memory is relatively common in CHF but cannot be accurately recognized by a screening neuropsychological test.

Activities of Daily Living↗

PubMed1989

Serotonergic dysfunction in depression.

Various irregularities in serotonin (5-HT) function have been postulated as causes of affective disorders. Serotonin has been related to many of the major symptoms of depression, e.g. mood, appetite, sleep, activity, and cognitive dysfunction. Interference with 5-HT synthesis or storage has been shown to induce depression in vulnerable individuals. Decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid, decreased plasma tryptophan, low tryptophan neutral amino acid ratio, abnormalities in serotonergic function indicated by neuroendocrine challenge tests and various platelet measures, have been reported in depressed patients. Concentrations of 5-HIAA, the major metabolite of 5-HT in plasma, were found to be significantly negatively correlated with severity of depression as measured by the Hamilton Rating Scale for Depression score and specific depressive symptoms, despite the fact that plasma 5-HIAA is largely peripheral in origin. Blood platelets, which have been suggested as models for serotonergic nerve terminals, have a significantly decreased number of 5-HT uptake sites and 3H-imipramine binding sites in depressed patients. Antidepressant drugs may act, in part, by enhancing serotonergic activity. The serotonergic deficit may occur at any of several levels: diminished availability of precursor, impaired activity of tryptophan hydroxylase, abnormalities in 5-HT release or uptake, 5-HT receptor abnormalities or interactions with other neurotransmitters.

Bipolar Disorder↗

PubMed2005

Comparison of hydroxyethyl starch and ringer lactate as a prime solution regarding S-100beta protein levels and informative cognitive tests in cerebral injury.

BACKGROUND: Cognitive dysfunction (as an indicator of cerebral dysfunction after open heart surgery) was observed in as many as 70% of patients who underwent cardiopulmonary bypass. S-100beta protein is a sensitive indicator of cerebral injury. We aimed to compare the effects of hydroxyethyl starch and Ringer lactate prime solutions in the protection of cerebral tissue in cardiopulmonary bypass using serum S-100beta protein levels and informative cognitive tests. METHODS: Patients were randomized into two groups. Open heart surgery was performed by using hydroxyethyl starch solution in group 1 (n = 15) and Ringer lactate solution in group 2 (n = 15). Preoperative, perioperative, and postoperative S-100beta protein levels and informative cognitive test scores, clinical and operational characteristics of the patients were compared. RESULTS: A significant difference was found only between preoperative and postoperative results of verbal accuracy (human) test in group 1, whereas differences between preoperative and postoperative scores of continuous skill, verbal accuracy (human), verbal accuracy (animal), verbal accuracy (human-animal), go-no-go paradigm, calculation, and abstract thinking tests were significant in group 2 (p < or = 0.05). The S-100beta protein levels were not significantly different between the groups (group p = 0.97). CONCLUSIONS: Because hydroxyethyl starch prime solution used in extracorporeal circulation had significant positive effects with informative-cognitive tests when compared to Ringer lactate solution, it seems to be a better prime solution to prevent cerebral dysfunction in these patients.

Cardiopulmonary Bypass↗

PubMed1999

Effects of S-8510, a benzodiazepine receptor partial inverse agonist, on event-related potentials (P300) in monkeys.

The present study investigated the effects of a novel benzodiazepine inverse agonist, S-8510 [2-(3-isoxazolyl)-3, 6, 7, 9-tetrahydroimidazo [4, 5-d] pyrano [4,3-b] pyridine monophosphate monohydrate], on the P300 components of the event-related potential (ERP) in monkeys. Late positive potentials (P300-like potentials) from the cortex (Pz) and hippocampus recorded using the auditory oddball paradigm in combination with electrical reinforcement can be measured in rhesus monkeys. The latency of this P300-like potential recorded from the monkey cortex was 330 ms, and the amplitude was 13 microV. It was prolonged in both the cortex (Pz) and hippocampus by SC injection of 10 microg/kg scopolamine, a muscarinic receptor antagonist. Oral administration of S-8510 (3, 10 mg/kg) had no effect on the latency in normal monkeys. However, S-8510 reversed the scopolamine-induced prolongation of P300-like potentials on the cortex (Pz) and hippocampus. These results show that S-8510 can attenuate the effects induced by scopolamine on P300-like potentials associated with cognitive function in monkeys, suggesting that S-8510 may be useful as a therapeutic drug in disease-associated cognitive dysfunctions of the central nervous system.

Animals↗

PubMed1994

Cognitive functions of cortical ACh: lessons from studies on trans-synaptic modulation of activated efflux.

Trans-synaptic modulation of cortical ACh efflux is a useful approach for determining the functions of cortical ACh. Bilateral modulation of basal forebrain GABAergic transmission by benzodiazepine-receptor agonists and inverse agonists decreases and increases, respectively, activated cortical ACh efflux. The determination of behavioral functions which are mediated via activated cortical ACh efflux, and therefore subject to the effects of basal forebrain GABA-cholinergic manipulations, should promote analyses of the functions of cortical ACh. Trans-synaptic approaches to enhance activated cortical ACh efflux offer some potential for the treatment of cognitive dysfunctions associated with impaired cortical cholinergic transmission.

Acetylcholine↗

PubMed2003

A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults.

OBJECTIVES: To determine whether cardiorespiratory fitness at baseline is associated with maintenance of cognitive function over 6 years or with level of cognitive function on tests performed 6 years later in a longitudinal study of healthy older people. DESIGN: Prospective cohort. SETTING: Community-based study of noninstitutionalized adults aged 55 and older living in Sonoma, California. PARTICIPANTS: Three hundred forty-nine cohort members without evidence of cardiovascular disease, musculoskeletal disability, or cognitive impairment at baseline. MEASUREMENTS: Cardiorespiratory fitness measures were based on a standard treadmill exercise test protocol and included peak oxygen consumption (peak VO2), treadmill exercise duration, and oxygen uptake efficiency slope (OUES). Cognitive function was evaluated at baseline with a modified Mini-Mental State Examination (mMMSE) and after 6 years of follow-up with a detailed cognitive test battery that included the full MMSE, three tests of attention/executive function, two measures of verbal memory, and two tests of verbal fluency. RESULTS: Participants with worse cardiorespiratory fitness at baseline experienced greater decline on the mMMSE over 6 years (mean mMMSE decline (95% confidence interval) by baseline peak VO2 tertile: lowest = -0.5 (-0.8 to -0.3), middle = -0.2 (-0.5-0.0), highest = 0.0 (-0.3-0.2), P =.002 for trend over tertiles). Participants with worse baseline cardiorespiratory fitness also performed worse on all cognitive tests conducted 6 years later. Results were similar for analyses based on peak VO2, treadmill exercise duration, and OUES. After adjustment for demographic and health-related covariates, measures of cardiorespiratory fitness were associated most strongly with measures of global cognitive function and attention/executive function. CONCLUSION: Baseline measures of cardiorespiratory fitness are positively associated with preservation of cognitive function over a 6-year period and with levels of performance on cognitive tests conducted 6 years later in healthy older adults. High cardiorespiratory fitness may protect against cognitive dysfunction in older people.

Aged↗

PubMedDate not supplied

High-level language difficulties in Parkinson's disease.

Twenty-six subjects with idiopathic Parkinson's disease (PD) and normal cognitive status (as measured by the Mini-Mental State Examination) were examined with a battery of tests selected to reveal subtle and/or high-level language impairments. The test battery included 'repetition of long sentences', 'recreating sentences', 'making inferences', 'comprehension of logico-grammatical sentences', 'comprehension of ambiguous sentences' and 'comprehension of metaphors', 'word definitions', 'word fluency', 'naming', 'sentence analysis' and 'morphological completion'. Comparisons were made between the PD subjects and 26 control subjects matched for age, gender and level of education. Significant differences in performance between the PD subjects and the control subjects were found in the ability to make inferences and to analyse sentences (state the correct number of words in a read sentence). An additional four subjects with different degrees of cognitive dysfunction were also investigated and were found to have particular problems in making inferences, recreating sentences and comprehending metaphors and ambiguities. The results suggest that processing implied information might be a specific problem in this group and that the task of making inferences could be a particularly sensitive test of high-level language dysfunction.

Adult↗

PubMed1997

Comparisons of restraint use in nursing homes in eight countries.

BACKGROUND: the use of restraints in nursing homes varies among countries and institutions. However, in many countries, no reliable data exist, although restraints use is acknowledged. METHOD: we compare data of the type of restraints used (trunk, limb or chair that prevents rising) and the intensity of its use in eight countries: Denmark, France, Iceland, Italy, Japan, Spain, Sweden and the USA. We report these data in total and for groups of residents with similar functional abilities and cognitive performance, thus avoiding to a certain extent the case-mix differences between samples from different countries. RESULTS: the total use of restraints in these cross-sectional samples showed a very low prevalence in Denmark, Iceland and Japan (less than 9%). Between 15 and 17% were seen in France, Italy, Sweden and the USA, while Spain showed almost 40%. These major differences among the countries persist, even when one controls for physical and cognitive abilities. There are also differences in the types and intensity of restraints used in different countries. In all countries, there is a constant increase in use of restraints with increasing activities of daily living difficulties and cognitive dysfunction.

Activities of Daily Living↗

PubMed2003

Adjuvant breast cancer treatment and cognitive function: current knowledge and research directions.

Evidence is mounting that potentially curative systemic adjuvant therapy for early-stage breast cancer may result in cognitive impairment. Five published studies have investigated cognitive function in this setting, and the consistent results of all five studies suggest an adverse effect of adjuvant chemotherapy. These studies are reviewed with particular attention to their methodologic limitations. For example, all five studies used cross-sectional designs, none controlled for possible confounding hormonal factors, and three examined patients who had not received a uniform chemotherapy regimen. The potential roles of chemotherapy-induced menopause and of adjuvant hormonal therapy in cognitive impairment are also discussed. Priorities for future research include confirmation of an effect of adjuvant chemotherapy in a study with a longitudinal design, closer examination of the potential contribution of hormonal factors, and similar studies on the effect of adjuvant therapy on cognitive function in other cancer types. If an effect of systemic adjuvant therapy on cognitive function is confirmed, such an effect will have implications for informed consent. It may also result in incorporation of objective measures of cognition in clinical trials of adjuvant therapy and in the investigation of preventive interventions that might minimize the impact of cognitive dysfunction after cancer treatment.

Antineoplastic Agents, Hormonal↗