Decrements In Cognitive Function Research Articles

A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus

Aims/hypothesisType 2 diabetes mellitus is associated with moderate decrements in cognitive functioning, mainly in verbal memory, information-processing speed and executive functions. How this cognitive profile evolves over time is uncertain. The present study aims to provide detailed information on the evolution of cognitive decrements in type 2 diabetes over time.MethodsSixty-eight patients with type 2 diabetes and 38 controls matched for age, sex and estimated IQ performed an elaborate neuropsychological examination in 2002–2004 and again in 2006–2008, including 11 tasks covering five cognitive domains. Vascular and metabolic determinants were recorded. Data were analysed with repeated measures analysis of variance, including main effects for group, time and the group × time interaction.ResultsPatients with type 2 diabetes showed moderate decrements in information-processing speed (mean difference in z scores [95% CI] −0.37 [−0.69, −0.05]) and attention and executive functions (−0.25 [−0.49, −0.01]) compared with controls at both the baseline and the 4 year follow-up examination. After 4 years both groups showed a decline in abstract reasoning (−0.16 [−0.30, −0.02]) and attention and executive functioning (−0.29 [−0.40, −0.17]), but there was no evidence for accelerated cognitive decline in the patients with type 2 diabetes as compared with controls (all p > 0.05).Conclusions/interpretationIn non-demented patients with type 2 diabetes, cognitive decrements are moderate in size and cognitive decline over 4 years is largely within the range of what can be viewed in normal ageing. Apparently, diabetes-related cognitive changes develop slowly over a prolonged period of time.

Blood pressure levels in pre‐diabetic stages are associated with worse cognitive functioning in patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is associated with mild decrements in cognitive functioning, but the relation of these decrements to metabolic and vascular risk factors is unclear. The present study compared the vascular risk factor profile over the preceding 16 years between T2DM patients with good cognitive functioning and those with poor cognitive functioning. The Hoorn study is a population-based cohort study on glucose metabolism and vascular disease initiated in 1989, with follow-up examinations in 1996-1998, 2000-2001 and 2005-2007. Cognitive functioning was assessed in 2005-2007. Patients who developed T2DM between 1989 and 2000-2001 (n = 64) were divided in tertiles (lowest tertile = 'poor cognition', highest tertile = 'good cognition') according to a sum score for performance across cognitive domains (SUM) and the domain score for information-processing speed (IPS). The time course of vascular risk factors from 1989 to 2005-2007 was compared between these tertiles with linear mixed models adjusted for age, sex and estimated IQ. Present levels (2005-2007) of vascular risk factors did not differ between patients with relatively poor or good cognition. However, patients with poor cognition had a 14-18 mmHg higher systolic blood pressure in 1989 than patients with good cognition. There were no differences in lipid profile and body weight at any time during the study between the groups. For IPS the T2DM patients with poor cognition even had a lower baseline HbA(1c) level than patients with good cognition. Cognitive dysfunction in T2DM is related to the cumulative effects of long-term exposure to hypertension, even in pre-DM stages.

Carotid Intimal Medial Thickness Predicts Cognitive Decline Among Adults Without Clinical Vascular Disease

Though clinical cardiovascular and cerebrovascular diseases are established risk factors for cognitive decline and dementia, less is known about the relations between vascular health and cognition among individuals without these diseases. Carotid intimal medial thickness (IMT), a measure of subclinical vascular disease, is associated with concurrent decrements in cognitive function, but relatively little research has examined longitudinal relations between carotid IMT and prospective cognitive decline. We examined relations of carotid IMT to prospective trajectories of cognitive function among 538 (aged 20 to 93, 39% male, 66% white) participants in the Baltimore Longitudinal Study of Aging (BLSA) free of known cardiovascular, cerebrovascular, and neurological disease. Participants underwent initial carotid ultrasonography and repeat neuropsychological testing on up to 8 occasions over up to 11 years of follow-up. Mixed-effects regression analyses were adjusted for age, gender, race, education, mean arterial pressure, body mass index, total cholesterol, smoking, depressive symptoms, and cardiovascular medication use. Individuals with greater carotid IMT displayed accelerated decline in performance over time on multiple tests of verbal and nonverbal memory, as well as a test of semantic association fluency and executive function. Carotid IMT predicts accelerated cognitive decline, particularly in the domain of memory, among community-dwelling individuals free of vascular and neurological disease.

Evaluating the Dimensionality of Perceived Cognitive Function

Decrements in cognitive function are common in cancer patients and other clinical populations. As direct neuropsychological testing is often not feasible or affordable, there is potential utility in screening for deficits that may warrant a more comprehensive neuropsychological assessment. Furthermore, some evidence suggests that perceived cognitive function (PCF) is independently associated with structural and functional changes on neuroimagery, and may precede more overt deficits. To appropriately measure PCF, one must understand its components and the underlying dimensional structure. The purpose of this study was to examine the dimensionality of PCF in people with cancer. The sample included 393 cancer patients from four clinical trials who completed a questionnaire consisting of the prioritized areas of concerns identified by patients and clinicians: self-reported mental acuity, concentration, memory, verbal fluency, and functional interference. Each area contained both negatively worded (i.e., deficit) and positively worded (i.e., capability) items. Data were analyzed by using Cronbach's alpha, item-total correlations, one-factor confirmatory factor analysis, and a bi-factor analysis model. Results indicated that perceived cognitive problem items are distinct from cognitive capability items, supporting a two-factor structure of PCF. Scoring of PCF based on these two factors should lead to improved assessment of PCF for people with cancer.

Cognitive Functioning in Elderly Persons with Type 2 Diabetes and Metabolic Syndrome: the Hoorn Study

Background/Aims: Type 2 diabetes mellitus (DM2) is associated with mild decrements in cognitive functioning, particularly in the elderly. It is often preceded by a ‘prediabetic stage’, characterized by the co-occurrence of insulin resistance and vascular risk factors, usually referred to as the metabolic syndrome. Cognitive decrements may already develop in these early stages. Methods: Cognitive functioning was compared cross-sectionally between DM2 patients (n = 64), patients with metabolic syndrome but without DM2 (n = 83) and control subjects (n = 100) participating in the prospective population-based Hoorn study. Participants performed an extensive neuropsychological examination. Vascular and metabolic determinants were recorded. Results: Both the DM2 group and the metabolic syndrome group performed worse than controls on the domains of information processing speed and attention and executive functioning (mean differences in z-scores 0.2–0.3, all p < 0.05). There were no significant differences in performance between the DM2 and metabolic syndrome group. None of the individual risk factors of the metabolic syndrome, measured at either the present or the previous examination, was a key determinant of cognitive functioning. Conclusion: These results show that DM2-associated cognitive decline may develop in early stages of the disease, possibly in relation to risk factors clustered in the metabolic syndrome.

Cognitive function in untreated hypothyroidism and hyperthyroidism

The brain is an important target organ for thyroid hormone, and alterations in mood and cognition may occur with thyroid dysfunction. Recent advances in the field of cognitive neurosciences have allowed more sensitive and focused testing of cognitive domains in patients with altered thyroid function. Based on recent population-based studies, there do not appear to be major deficits in cognitive functioning in overt or subclinical thyroid disease. However, interventional and functional imaging studies suggest that subtle deficits in specific cognitive domains probably do exist. The most commonly affected domains are working memory and executive function. Also present are alterations in mood, manifested by increased rates of depressive and anxiety symptoms. Patients with overt or subclinical thyroid dysfunction commonly complain of decrements in cognitive function, but studies suggest that such decrements are most likely to be minor or not related to the thyroid dysfunction. More common are mood alterations, which often improve with treatment.

Acetyl-L-carnitine and α-lipoic acid: possible neurotherapeutic agents for mood disorders?

Background: Mood disorders are associated with decrements in cognitive function, which are insufficiently treated with contemporary pharmacotherapies. Objectives: To evaluate the putative neurotherapeutic effects of the mitochondrial cofactors, L-carnitine, acetyl-L-carnitine, and α-lipoic acid; and to provide a rationale for investigating their efficacy in the treatment of neurocognitive deficits associated with mood disorders. Methods: A PubMed search of English-language articles published between January 1966 and March 2007 was conducted using the search terms carnitine and lipoic acid. Results: L-carnitine and α-lipoic acid may offer neurotherapeutic effects (e.g., neurocognitive enhancement) via disparate mechanisms including antioxidant, anti-inflammatory, and metabolic regulation. Preliminary controlled trials in depressed geriatric populations also suggest an antidepressant effect with acetyl-L-carnitine. Conclusions: L-carnitine and α-lipoic acid are pleiotropic agents capable of offering neuroprotective and possibly cognitive-enhancing effects for neuropsychiatric disorders in which cognitive deficits are an integral feature.

Risk factors for somnolence, edema, and hallucinations in early Parkinson disease

The CALM-PD trial evaluated the development of motor complications in subjects with early Parkinson disease (PD) randomized to initial treatment with either pramipexole or levodopa. A secondary finding of the trial was a higher than anticipated development or worsening of somnolence and edema and development of hallucinations. To investigate risk factors for somnolence, edema, and hallucinations in patients with early PD initiating dopaminergic therapy. This was a secondary analysis of data from the CALM-PD trial. Baseline patient characteristics were evaluated for their associations with the development or worsening of somnolence and edema and the development of hallucinations using Cox proportional hazards regression models. Kaplan-Meier estimates of the 4-year incidence of the development or worsening of somnolence and edema and the development of hallucinations were 35%, 45%, and 17%. Initial pramipexole treatment (hazard ratio [HR] 2.22, 95% CI 1.41, 3.50, p < 0.001), male gender (HR 1.79, 95% CI 1.09, 2.93, p = 0.02), and >5 systems with a comorbid illness (HR 1.62, 95% CI 1.04, 2.51, p = 0.03) were associated with somnolence. Initial pramipexole treatment (HR 3.18, 95% CI 1.95, 5.18, p < 0.0001), female gender (HR 1.46, 95% CI 0.94, 2.27, p = 0.09), and comorbid cardiac disease (HR 1.59, 95% CI 1.02, 2.47, p = 0.04) were associated with edema. Age > or =65 (HR 2.06, 95% CI 0.98, 4.32, p = 0.06), Mini-Mental State Examination score >28 (HR 0.42, 95% CI 0.19, 0.91, p = 0.03), and >5 systems with a comorbid illness (HR 3.42, 95% CI 1.59, 7.38, p = 0.002) were associated with hallucinations. Comorbid illnesses are important and overlooked risk factors for the development of somnolence, edema, and hallucinations. When initiating therapy with pramipexole, patients should be counseled about and monitored for somnolence and edema. Slight decrements in cognitive function and older age are associated with an increased risk of hallucinations.

Cognitive Status, Stroke Symptom Reports, and Modifiable Risk Factors Among Individuals With No Diagnosis of Stroke or Transient Ischemic Attack in the RE asons for G eographic and R acial D ifferences in S troke (REGARDS) Study

Vascular disorders that increase risk for stroke may be accompanied by decrements in cognitive functioning and by stroke symptoms in the absence of diagnosed stroke or transient ischemic attack. This study evaluates relationships among cognitive status, stroke symptom reports, and cardiovascular and behavioral factors. REasons for Geographic and Racial Differences in Stroke (REGARDS), a prospective population study of stroke incidence, assesses stroke risk with telephone interviews and in-home physicals. Excluding subjects with a history of stroke or transient ischemic attack, this analysis includes 14,566 black and white men and women > or =45 years of age. Incremental logistic models examine baseline relationships among cognitive status (Six-item Screener scores), stroke symptom reports, demographics, health behaviors, cardiovascular indices, and depressive symptoms. A history of stroke symptoms was related to impaired cognitive status after adjusting for age, gender, race, and education but not after adjusting for poor health behaviors, vascular risk factors, and depressive symptoms. Odds of experiencing a stroke symptom increased 35% with each of five modifiable factors (hypertension, diabetes, smoking, lack of exercise, depressive symptoms), and odds of cognitive impairment increased an additional 12% with each modifiable factor. Lifelong abstinence from alcohol, lack of exercise, and depressive symptoms were independently related to impaired cognitive status. The increased likelihood of cognitive impairment among subjects reporting stroke symptoms in the absence of a diagnosed stroke or transient ischemic attack suggests that such symptoms are not benign and may warrant clinical evaluation that includes a cognitive assessment. Future studies that include brain imaging may clarify the etiology of these symptoms.

Personality Disorder Symptomatology and Neuropsychological Functioning in Closed Head Injury

Despite an emerging literature characterizing the neuropsychological profiles of borderline, antisocial, and schizotypal personality disorders, relations between personality disorder traits and neurocognitive domains remain unknown. The authors examined associations among Millon Clinical Multiaxial Inventory-III personality disorder scales and eight neuropsychological domains in 161 patients referred for neuropsychological evaluation following closed head injury. Most personality disorder scales were associated with some decrement in cognitive function, particularly speeded processing, executive function, and language, while histrionic and narcissistic scales had positive relations with neuropsychological functioning. Results suggest that many personality disorder traits are related to neurocognitive function, particularly those functions subserved by frontal and temporal regions.

Lead and cognitive function in adults: A questions and answers approach to a review of the evidence for cause, treatment, and prevention

Lead has been extensively used worldwide in gasoline, consumer products, commercial applications, and industrial settings. Its use in gasoline and paint has been particularly hazardous to public health leading to widespread population exposure and substantial lifetime cumulative doses in most Americans over age 40 years. Cumulative lead dose can be estimated by measuring the current concentration of lead in tibia bone by X-ray fluorescence. A growing literature has documented that tibia lead levels are associated with decrements in cognitive function and declines in cognitive function over time. Furthermore, there are several interesting lines of biochemical and epidemiological investigation that have demonstrated potential links of lead to neurodegenerative diseases. These studies support the inference that a proportion of what has been termed ‘normal’ age-related cognitive decline may, in fact, be due to exposure to neurotoxicants such as lead. Well-designed studies of cumulative lead dose and Alzheimer's disease risk should be conducted to follow-up on these leads. The strong and compelling body of literature on lead and cognitive dysfunction and decline also supports a need for intervention studies to prevent lead-related cognitive decline.

Environmental lead exposure and cognitive function in community-dwelling older adults

To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p <or= 0.01, one domain p <or= 0.05). Blood lead was not associated with any cognitive domain. Associations with tibia lead were attenuated after adjustment for years of education, wealth, and race/ethnicity. Independent of recent lead dose, retained cumulative dose resulting from previous environmental exposures may have persistent effects on cognitive function. A portion of age-related decrements in cognitive function in this population may be associated with earlier lead exposure.

The Effect of Alcohol on Athletic Performance

The use of alcohol is often intimately associated with sport. As well as providing a source of energy, alcohol (ethanol) has metabolic, cardiovascular, thermoregulatory, and neuromuscular actions that may affect exercise performance. Strength is minimally affected, and performance impairments depend on the dose of alcohol and subject habituation to alcohol intake, exercise duration, environmental conditions, and other factors. Central nervous system function is impaired at high doses, resulting in decrements in cognitive function and motor skill, as well as behavioral changes that may have adverse effects on performance. Effects may persist for hours after intoxication.

Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain

Chronic opioid therapy is commonly prescribed for chronic nonmalignant pain. Few published data describe the adverse effects experienced by patients with chronic nonmalignant pain being treated by primary care physicians. A prevalence study was conducted on a sample of 1,009 patients (889 receiving chronic opioids) being treated by 235 primary care physicians. Standardized questionnaires and medical record reviews were used to assess rates of addiction, pain diagnosis and severity, opioid adverse effects, and mental health. The mean daily dose of opioids was 92 mg using a morphine-equivalent conversion. Side effects included constipation (40 percent), sleeping problems (25 percent), loss of appetite (23 percent), and sexual dysfunction (18 percent), with patients on daily opioids experiencing more side effects than subjects on intermittent medication. The Medical Outcomes Study Mental Health Inventory (MOS-MHI) cognitive functioning scale indicated poorer cognitive function in the overall sample of chronic pain patients as compared to a general clinical sample (delta x 95 percent CI = 9.28, 13.76). However, there were limited differences in MOS scores between chronic pain subjects on daily opioids vs. intermittent opioids vs. no prescription opioids. A regression model suggests that psychological measures and pain severity are more predictive of decrements in cognitive function than specific opioid preparations or daily opioid dose. Physicians should closely monitor patients for adverse effects and adequacy of pain control when using chronic opioid therapy for chronic pain treatment. Psychological health, an important predictor of cognitive dysfunction, is a particularly important measure to actively monitor and manage.

Newborn Screening Technology: Proceed With Caution

The American College of Medical Genetics (ACMG) recommends a significant expansion in the number of conditions targeted by newborn screening (NBS) programs.1 In this commentary we advocate a more cautious approach. NBS dates to the early 1960s, when the technology developed to conduct large-scale testing on dried blood spots for phenylketonuria (PKU).2 PKU remains the paradigm condition for NBS because of features of the disease and its treatment, which are particularly advantageous to population screening. It is a condition that silently causes neurologic devastation but is amenable to early detection and effective prevention with a diet of moderate burden and complexity.3 Many children affected with PKU and their families have benefited from state screening programs over the past 4 decades because of collaboration between health departments, families, primary care providers, and metabolic specialists. However, PKU screening is not an unmitigated success.4,5 There was initial uncertainty about whether children with variant forms of hyperphenylalaninemia required treatment and about whether affected children require life-long dietary management.6 Indeed, some children with benign conditions were seriously harmed from unnecessary restrictions in their diets.5 In addition, long-term studies demonstrate decrements in cognitive function for affected children and adolescents who are not fully adherent to the diet,7,8 yet adherence to the diet is challenging because of its poor palatability, high cost, and limits on insurance coverage in many policies. Affected women who are off the diet are at high risk of bearing severely neurologically impaired children.9 Only recently have many programs begun tracking affected women to enable notification, education, and management. These difficulties by no means negate the value of NBS for PKU, but they highlight the problems with the successful implementation of a population-based screening program even when a model condition is targeted. … Address correspondence to Jeffrey R. Botkin, MD, MPH, Research Administration Building, 75 South 2000 East #108, Salt Lake City, UT 84112-8930. E-mail: jeffrey.botkin{at}hsc.utah.edu

High-Sensitivity C-Reactive Protein and Cognitive Function in Older Women

Inflammatory processes may be involved in the development of dementia, although findings from epidemiologic studies directly examining inflammatory markers and dementia or its precursor, impaired cognitive function, are inconsistent. We measured plasma levels of the inflammatory marker, C-reactive protein, using a high-sensitivity assay (hs-CRP) in 4,231 older participants of the Women's Health Study, who provided blood samples between 1992 and 1996 when they were age 60 to 90 years. From 1998 to 2000, we administered a battery of 5 cognitive tests measuring general cognition, verbal memory, and category fluency. Using multiple linear regression, we compared mean cognitive test scores across quintiles of hs-CRP, adjusting for potential confounding factors. There was a wide distribution of hs-CRP levels among these women, and a large proportion had levels considered to reflect a high risk of cardiovascular disease. We observed no suggestion, however, that higher hs-CRP levels were associated with poorer cognitive performance. For example, on a global score combining results of all the cognitive tests, mean scores among women in the highest quintile of hs-CRP did not differ from those in the lowest quintile (multivariable-adjusted mean difference = 0.04; 95% confidence interval [CI]: -0.02 to 0.11, P for trend across quintiles = 0.38). Overall, in these women, we found no evidence of a link between hs-CRP, a marker of inflammation, and decrements in cognitive function.

Perceived Cognitive Function and Emotional Distress Following Coronary Artery Bypass Surgery

Many patients experience decrements in cognitive function and emotional adjustment following coronary artery bypass graft (CABG) surgery. Moreover, cognitive decline and emotional distress are often positively related. This study evaluated the cross-sectional and prospective associations of emotional and subjective cognitive complaints, to assess the hypothesis that they would be mutually reinforcing. Participants were 76 CABG patients recruited from Akron General Medical Center. Depression and anxiety symptoms and perceived cognitive difficulties were evaluated at a baseline postsurgical visit and re-assessed 5 months later. Emotional symptoms and perceived cognitive difficulties were significantly related both within and across time. After controlling for numerous potential confounds, baseline perceived cognitive difficulties predicted a more negative course of emotional symptoms during follow-up. Baseline emotional symptoms did not predict the course of perceived cognitive difficulties. Perceptions of cognitive decline may contribute to emotional distress in patients post-CABG.

Alterações neuropsicológicas em dependentes de cocaína/crack internados: dados preliminares

Although cocaine use is a significant public health problem, there is relative paucity of scientific data on long-term neurocognitive consequences of the exposure to the substance. This study examined the association between crack cocaine dependence and neuropsychological performance. An extended battery of neuropsychological tests was administered to 15 abstinent cocaine abusers, inpatients in abstinence for two weeks, and 15 non-drug-using control subjects matched for age, gender, education, socio-economic status, handedness and IQ. The preliminary findings showed statistical significance (p<0.05) on differences of performance in attention, verbal fluency, verbal memory, visual memory, learning ability and executive functions. These results represent evidences that cocaine abuse is associated with decrements in cognitive functioning, similar to cognitive disorders associated to prefrontal and temporal brain impairments. Knowledge of specific cognitive deficits in cocaine abusers may be useful for designing more effective substance abuse prevention and treatment programs.

Cognitive functioning in children with sickle cell disease: a meta-analysis.

To establish whether sickle cell disease (SCD) affects cognitive functioning in children with no evidence of cerebral infarction. We conducted a meta-analysis of studies of cognition in SCD to determine the size of any statistical difference between children with SCD and controls. Methodological factors were evaluated according to the size and frequency of group differences. There were small but reliable decrements in cognitive functioning on IQ measures (4.3-point difference overall). The most methodologically rigorous studies showed a highly similar pattern. Sampling issues associated with the effect size for IQ were identified. Measures of specific abilities appear more sensitive than IQ scores to cognitive decrements in SCD. SCD is associated with cognitive effects even in the absence of cerebral infarction. The causes of this cognitive decrement may include direct effects of SCD on brain function or indirect effects of chronic illness.

Effects of acute hyperglycemia on mental efficiency and counterregulatory hormones in adolescents with insulin-dependent diabetes mellitus

Objective: To determine whether acute hyperglycemia adversely affects mental efficiency to the same extent as acute mild hypoglycemia. Study design: We administered a battery of cognitive tests to adolescents studied at hyperglycemic (20 mmol/L [360 mg/dl]), hypoglycemic (3.3 mmol/L [60 mg/dl]), or euglycemic (5.5 mmol/L [100 mg/dl]) targets, which were maintained by an insulin-glucose clamp. The study included 36 children, 9 to 19 years of age (mean = 14.7 years), with diabetes duration more than 2 years (mean = 6.9 years). Results: Cognitive test performance did not deteriorate during hyperglycemia. In contrast, there was a significant decline in performance on all cognitive tests during mild hypoglycemia. Autonomic symptoms did not change significantly during hyperglycemia or during the rapid return from hyperglycemia to euglycemia. Although significant increments in epinephrine and pancreatic polypeptide levels occurred during mild hypoglycemia, no changes in counterregulatory hormones occurred during hyperglycemia. An exploratory regression analysis demonstrated that changes in mental efficiency were best predicted by increases in pancreatic polypeptide, a marker of autonomic activation. Conclusion: These results confirm our previous finding that mild hypoglycemia causes transient decrements in cognitive function. In contrast, neither hyper glycemia, nor the rapid drop from acute hyperglycemia to euglycemia, affected symptoms, cognitive function, or counterregulatory hormone secretion. (J P EDIATR 1995;126:178-84)