Cognitive Decline

Objective: To assess prospectively the degree of postrecovery long-term cognitive decline after moderate to severe traumatic brain injury (TBI). Design: Observational cohort. Setting: Inpatient rehabilitation hospital. Participants: Adults (Nϭ33) with moderate and severe TBI from a well characterized sample with low attrition. Interventions: Not applicable. Main Outcome Measures: Recovery of functioning was ascertained through repeat neuropsychological assessments over the first 5 years postinjury. Cognitive decline from a baseline of 12 months postinjury to a follow-up evaluation conducted on average Ϯ SD 2.1Ϯ0.99 years later. Change was calculated using the reliable change index (RCI) for 12 neuropsychological tests commonly used in the assessment of TBI. Results: At the group level, negligible changes in cognitive function were observed over time. However, application of the RCI using 90% confidence intervals showed statistically significant cognitive decline on at least 2 neuropsychological measures in 27.3% of study participants. Decline was most commonly observed on a test of verbal fluency and the delayed recall portion of a test of verbal list learning (Rey Auditory Verbal Learning Test), although substantial variability existed across patients. Decline was significantly correlated with hours of therapy received at 5 months postinjury (PϽ.02). Conclusions: Consistent with a small number of previous studies, cognitive deterioration may follow an initial period of recovery. Overall, the pattern of decline across tests varied across individuals. Possible mechanisms of decline are discussed. Further research is needed to understand the stability of this finding and its functional implications.

Summary: Rasmussen encephalitis is a chronic, progres- sive inflammation of the brain of unknown origin. Early diagnosis and treatment with immunoactive agents and/or hemispherectomy are sought to prevent the progressive cognitive decline that accompanies this disease. Combined anatomic and functional neuroimaging may serve to focus the diagnostic workup and to hasten brain biopsy for de- finitive diagnosis. Two biopsy proved

We investigated whether smoking is a risk factor for relative cognitive decline from age 11 to 64 years. The potentially confounding effects of childhood IQ, occupational status, level of education, presence of heart disease, hypertension, and lung function were examined. Subjects were nondemented and living independently. They were all born in 1936, had been participants in the same Scottish national IQ survey in 1947, and were reexamined at age about 64 years in 2000-2002. Current smokers and nonsmokers had significantly different mental test scores at age 64. This difference remained after adjustment for childhood IQ. Multiple linear regression identified childhood IQ, level of education, occupational code, lung function, and smoking history as significant independent predictors of mental function at age 64. In this sample, smoking makes a small (< 1% variance) independent negative contribution to cognitive aging.

Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.

Rising life expectancies coupled with an increasing awareness of age-related cognitive decline have led to the unwarranted use of psychopharmaceuticals, including acetylcholinesterase inhibitors (AChEIs), by significant numbers of healthy older individuals. This trend has developed despite very limited data regarding the effectiveness of such drugs on non-clinical groups and recent work indicates that AChEIs can have negative cognitive effects in healthy populations. For the first time, we use a combination of EEG and simultaneous EEG/fMRI to examine the effects of a commonly prescribed AChEI (donepezil) on cognition in healthy older participants. The short-and long-term impact of donepezil was assessed using two double-blind, placebo-controlled trials. In both cases, we utilised cognitive (paired associates learning (CPAL)) and electrophysiological measures (resting EEG power) that have demonstrated high-sensitivity to age-related cognitive decline. Experiment 1 tested the effects of 5 mg/per day dosage on cognitive and EEG markers at 6-hour, 2-week and 4-week followups. In experiment 2, the same markers were further scrutinised using simultaneous EEG/fMRI after a single 5 mg dose. Experiment 1 found significant negative effects of donepezil on CPAL and resting Alpha and Beta band power. Experiment 2 replicated these results and found additional drug-related increases in the Delta band. EEG/fMRI analyses revealed that these oscillatory differences were associated with activity differences in the left hippocampus (Delta), right frontal-parietal network (Alpha), and default-mode network (Beta). We demonstrate the utility of simple cognitive and EEG measures in evaluating drug responses after acute and chronic donepezil administration. The presentation of previously established markers of age-related cognitive decline indicates that AChEIs can impair cognitive function in healthy older individuals. To our knowledge this is the first study to identify the precise neuroanatomical origins of EEG drug markers using simultaneous EEG/fMRI. The results of this study may be useful for evaluating novel drugs for cognitive enhancement.

Social behavioral abnormalities are commonly seen in the later stages of dementia. However, there has been only limited empirical study of social functioning in the earlier stages of the disease, or in individuals diagnosed with mild cognitive impairment (MCI). The aim of the present study was to test whether these clinical groups show more socially inappropriate and prejudicial behavior relative to controls, as rated by informants. No group differences were identified for ratings of either socially appropriate behavior or stereotyping and prejudice. However, the results also indicated that informants rated participants with dementia as showing the most inappropriate behavior, and that these ratings were related to participants' degree of immediate logical memory impairment, but not to delayed memory recall or to more general neurocognitive decline as indexed by the Mini Mental State Examination. Together, these results have implications for an understanding of some of the changes in social function seen in abnormal adult aging.

Previous studies have shown an association between diabetes mellitus and impairments in learning and memory. These deficits were partially reversed by the use of insulin. Due to the fact that exercise has positive effects on many physiological systems, including the central nervous system, the present study, evaluated the effects of treadmill running on spatial learning and memory in streptozotocin (STZ)-induced diabetic rats. The exercise program was treadmill running at 17 meters per minute (m/min) at 0 • inclination for 40 minutes per day (min/day), 7 days/week, for 12 weeks. Experimental groups were: the control-rest, the control-exercise, the diabetes-rest and the diabetes-exercise. Spatial learning and memory was investigated by Morris water maze test in the rats after 12 weeks of diabetes induction and the exercise period. Our data showed that spatial learning and memory was significantly impaired in the diabetes-rest group with respect to the control-rest group. However, there were no differences between the other groups. The present results suggest that spatial learning and memory is affected under diabetic conditions and that treadmill running prevents these effects. The data correspond to the possibility that treadmill running is helpful in the prevention and alleviation of the cognitive decline in diabetes mellitus.

With 90% of neuroscience clinical trials failing to see efficacy, there is a clear need for the development of disease biomarkers that can improve the ability to predict human Alzheimer's disease (AD) trial outcomes from animal studies. Several lines of evidence, including genetic susceptibility and disease studies, suggest the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) as a potential biomarker with congruency between humans and animal models. For example, early in AD, patients present with decreased glucose metabolism in the entorhinal cortex and several regions of the brain associated with disease pathology and cognitive decline. While several of the commonly used AD mouse models fail to show all the hallmarks of the disease or the limbic to cortical trajectory, there has not been a systematic evaluation of imaging-derived biomarkers across animal models of AD, contrary to what has been achieved in recent years in the Alzheimer's Disease Neuroimaging Initiative (ADNI) . If animal AD models were found to mimic endpoints that correlate with the disease onset, progression, and relapse, then the identification of such markers in animal models could afford the field a translational tool to help bridge the preclinical-clinical gap. Using a combination of FDG-PET and functional magnetic resonance imaging (fMRI), we examined the Tg2576 mouse for global and regional measures of brain glucose metabolism at 7 and 19 months of age. In experiment 1 we observed that at younger ages, when some plaque burden and cognitive deficits have been reported, Tg2576 mice showed hypermetabolism as assessed with FDG-PET. This hypermetabolism decreased with age to levels similar to wild type (WT) counterparts such that the 19-month-old transgenic (Tg) mice did not differ from age matched WTs. In experiment 2, using cerebral blood volume (CBV) fMRI, we demonstrated that the hypermetabolism observed in Tg mice at 7 months could not be explained by changes in hemodynamic parameters as no differences were observed when compared with WTs. Taken together, these data identify brain hypermetabolism in Tg2576 mice which cannot be accounted for by changes in vascular compliance. Instead, the hypermetabolism may reflect a neuronal compensatory mechanism. Our data are discussed in the context of disease biomarker identification and target validation, suggesting little or no utility for translational based studies using Tg2576 mice. (M. Day). Neurobiology of Aging 33 (2012) 933-944 www.elsevier.com/locate/neuaging 0197-4580/$ -see front matter

Currently available epidemiological evidence suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions, while increased polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) may be protective against cognitive decline. In a Southern Italian elderly population from the Italian Longitudinal Study on Aging (ILSA), a clear reduction of risk of age-related cognitive decline (ARCD) has been found with elevated intake of PUFA and MUFA. Furthermore, in the ILSA, while dietary fatty acids intakes were not associated with incident mild cognitive impairment (MCI), high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development of MCI. These epidemiological findings on predementia syndromes, i.e. MCI or ARCD, together with a recent randomised controlled trial on a possible effect on cognitive and depressive symptoms of ω-3 PUFA supplementation in patients with very mild AD, suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia.

Two studies explored the stability of art preference in patients with Alzheimer's disease and age-matched control participants. Preferences for three different styles of paintings, displayed on art postcards, were examined over two sessions. Preference for specific paintings differed among individuals but AD and non-AD groups maintained about the same stability in terms of preference judgments across two weeks, even though the AD patients did not have explicit memory for the paintings. We conclude that aesthetic responses can be preserved in the face of cognitive decline. This should encourage caregivers and family to engage in arts appreciation activities with patients, and reinforces the validity of a preference response as a dependent measure in testing paradigms. Press for referring patients to us. We also acknowledge the help of Meredith Hickory who tested patients in Experiment 1 and Allen and Jason Schweinsberg who provided assistance in interpreting the mathematical properties of the rank change score.

The Mini-Mental State Examination (MMSE; M. F. Folstein, S. E. Folstein, & P. R. and the Modified MMSE (E. L. were compared psychometrically. In this study, 525 community-dwelling participants, aged 65-89, were divided into 2 groups: no cognitive impairment (NCI; n -406) and Alzheimer's disease (n = 119). Both tests yielded comparable reliability estimates. Fewer years of education decreased specificity and increased sensitivity, whereas increasing age primarily decreased specificity. It is concluded that although the 2 tests produce comparable effects, the inclusion of a verbal fluency test would increase the sensitivity of the MMSE. Normative data for the NCI group, stratified for 2 age levels (65-79 and 80-89) and 2 educational levels (0-8 and 9+ years), are presented. Folstein, Folstein, and McHugh (1975) introduced the Mini-Mental State Examination (MMSE) as a brief, objective assessment of cognitive functioning and as a measure of changes in cognitive status. The MMSE usually can be administered in 5-10 min and has been employed extensively in clinical settings, community surveys, and epidemiological studies. In a recent review of the literature, Tombaugh and Mclntyre (1992) concluded that the MMSE possessed moderate to high reliability coefficients, demonstrated high levels of sensitivity for cognitive deficits in patients suffering from moderate to severe Alzheimer's disease, and reflected the cognitive decline typical of dementia patients. Criticisms of the MMSE included (a) its failure to discriminate between people with mild dementia and those who are not demented, (b) a limited ability to detect impairment caused by focal lesions, particularly those in the right hemisphere, (c) overly simple language items that reduce sensitivity to mild linguistic deficits, and (d) a large number of false-positive errors because of its bias against individuals with low education. In response to these problems, several attempts have been made to improve the MMSE. Of these, the Modified Mini-Mental State Examination (3MS; Teng & Chui, 1987) represents the most extensive revision. Teng and Chui (1987) added four additional subtests (date and place of birth, word fluency, similarities, and delayed recall of words). The maximum score was

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid β-peptide (Aβ) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD (3xTgAD mice). Groups of 3xTgAD mice were maintained on an ad libitum control diet, or CR or IF diets, beginning at 3 months of age. Half of the mice in each diet group were subjected to behavioral testing (Morris swim task and open field apparatus) at 10 months of age and the other half at 17 months of age. At 10 months 3xTgAD mice on the control diet exhibited reduced exploratory activity compared to nontransgenic mice and to 3xTgAD mice on CR and IF diets. Overall, there were no major differences in performance in the water maze among genotypes or diets in 10-month-old mice. In 17-month-old 3xTgAD mice the CR and IF groups exhibited higher levels of exploratory behavior, and performed better in both the goal latency and probe trials of the swim task, compared to 3xTgAD mice on the control diet. 3xTgAD mice in the CR group showed lower levels of Aβ1-40, Aβ1-42 and phospho-tau in the hippocampus compared to the control diet group, whereas Aβ and phospho-tau levels were not decreased in 3xTgAD mice in the IF group. IF may therefore protect neurons against adverse effects of Aβ and tau pathologies on synaptic function. We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Aβ and tau pathologies.

was a contributor to the design and conduct of this study. Dr. Mahncke is an employee of and holds stock options in Posit Science Corporation, the developer of the experimental training program. Ultimate responsibility for the design and conduct of the trial resided with the co-principal investigators, Drs. Glenn Smith and Elizabeth Zelinski. Neither Dr. Smith nor Dr. Zelinski are employees of or hold equity in posit Science Corporation. In addition, the sponsor contracted with Quintiles Transnational Corp, and independent biostatistician Kevin DeLucci, PhD, of the University of California, San Francisco, to provide the independent data management and analyses reported in this study. Conflict of Interest: The IMPACT Study was funded by Posit Science Corporation through research grants to Mayo Clinic Foundation and the University of Southern California. Patricia Housen received compensation from Posit Science for consulting services. Kristine Yaffe received compensation from Posit Science for consulting services and honoraria for speaking engagements. Ronald Ruff received compensation from Posit Science for consulting services. Henry W. Mahncke is an employee of and holds stock options in Posit Science Corporation, the developer of the experimental training program. Author Contributions: Glenn E. Smith helped develop the study concept and design; assisted with the acquisition, statistical analysis and interpretation of data; with the drafting of the manuscript; with obtaining funding; and with study supervision. He also contributed to the critical revision of the manuscript for important intellectual content. Patricia Housen assisted with the statistical analysis and interpretation of data and with drafting of the manuscript; provided administrative, technical, or material support; and contributed to the critical revision of the manuscript for important intellectual content. Kristine Yaffe assisted with the statistical analysis and interpretation of the data and contributed to the critical revision of the manuscript for important intellectual content. Ronald Ruff helped develop the study concept and design, assisted with the statistical analysis and interpretation of the data, and contributed to the critical revision of the manuscript for important intellectual content. Robert F. Kennison assisted with the statistical analysis and interpretation of the data and contributed to the critical revision of the manuscript for important intellectual content. Henry W. Mahncke assisted with the statistical analysis and interpretation of the data and with study supervision; provided administrative, technical or material support; and contributed to the critical revision of the manuscript for important intellectual content. Elizabeth M. Zelinski helped develop the study concept and design; assisted with the acquisition, statistical analysis, and interpretation of data; drafting of the manuscript; obtaining funding; and study supervision. She also contributed to the critical revision of the manuscript for important intellectual content.

Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient&#39;s clinical situation and adverse treatment effects. Radiotherapy has been regarded as the main cause of cognitive decline in these patients, because children with brain tumours can develop intellectual deterioration caused by radiotherapy. In long-term surviving patients, radiotherapy may indeed lead to cognitive deficits, or even dementia. Recent studies, however, have made clear that focal radiotherapy in patients with glioma is not the main reason for cognitive deficits. The tumour itself and other medical treatments contribute largely to the cognitive deficits. Cognitive function is now also recognised as an independent prognostic factor in the survival of glioma patients. Additionally, cognitive deterioration can be the first indicator of progressive disease after trea...

The effectiveness of two interventions, dietary fortification with antioxidants and a program of behavioral enrichment, was assessed in a longitudinal study of cognitive aging in beagle dogs. A baseline protocol of cognitive testing was used to select four cognitively equivalent groups: control food-control experience (C-C), control food-enriched experience (C-E), antioxidant fortified food-control experience (A-C), and antioxidant fortified food-enriched experience(A-E). We also included two groups of young behaviorally enriched dogs, one receiving the control food and the other the fortified food. Discrimination learning and reversal was assessed after one year of treatment with a size discrimination task, and again after two years with a black/white discrimination task. The four aged groups were comparable at baseline. At one and two years, the aged combined treatment group showed more accurate learning than the other aged groups. Discrimination learning was significantly improved by behavioral enrichment. Reversal learning was improved by both behavioral enrichment and dietary fortification. By contrast, the fortified food had no effect on the young dogs. These results suggest that behavioral enrichment or dietary fortification with antioxidants over a long-duration can slow age-dependent cognitive decline, and that the two treatments together are more effective than either alone in older dogs.

Background: High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking.

Previous studies have shown an association between diabetes mellitus and impairments in learning and memory. These deficits were partially reversed by the use of insulin. Due to the fact that exercise has positive effects on many physiological systems, including the central nervous system, the present study, evaluated the effects of treadmill running on spatial learning and memory in streptozotocin (STZ)-induced diabetic rats. The exercise program was treadmill running at 17 meters per minute (m/min) at 0 • inclination for 40 minutes per day (min/day), 7 days/week, for 12 weeks. Experimental groups were: the control-rest, the control-exercise, the diabetes-rest and the diabetes-exercise. Spatial learning and memory was investigated by Morris water maze test in the rats after 12 weeks of diabetes induction and the exercise period. Our data showed that spatial learning and memory was significantly impaired in the diabetes-rest group with respect to the control-rest group. However, there were no differences between the other groups. The present results suggest that spatial learning and memory is affected under diabetic conditions and that treadmill running prevents these effects. The data correspond to the possibility that treadmill running is helpful in the prevention and alleviation of the cognitive decline in diabetes mellitus.

The relationship between leisure activities and development of cognitive impairment in aging has been the subject of recent research. We examined television viewing in association with risk of developing Alzheimer's disease (AD) in a case-control study. Given recent focus on the importance of intellectually stimulating activities as preventive measures against cognitive decline, it is important to examine the eVects of less stimulating but common activities. Data are from 135 Alzheimer's disease cases and 331 healthy controls. Demographic characteristics and life history questionnaire responses on the number of hours spent on 26 leisure activities during middle-adulthood (ages 40-59) were analyzed. Logistic regression was used to examine the eVects of middle-adulthood leisure activities on case vs. control status. Results indicate that for each additional daily hour of middle-adulthood television viewing the associated risk of AD development, controlling for year of birth, gender, income, and education, increased 1.3 times. Participation in intellectually stimulating activities and social activities reduced the associated risk of developing AD. Findings are consistent with the view that participation in non-intellectually stimulating activities is associated with increased risk of developing AD, and suggest television viewing may be a marker of reduced participation in intellectually stimulating activities.  2004 Elsevier Inc. All rights reserved.

As the majority of the North American population continues to age, cognitive decline in older adults is becoming an ever-growing concern. With the increase in age comes a decrease in cerebral blood flow, slowing of the brain's alpha rhythm and increased theta activity. These changes correlate with reduced cognition, spanning memory, problem solving ability, difficulty with language and speech, and locomotion. Chronic stress impairs hippocampal function leading to a host of disorders including Alzheimer's disease. The left hemisphere of the brain has a tendency to loose functionality before the right side, which may enhance spatial creativity and when coupled with fears and feelings of helplessness, may also bring forth depression. Preliminary studies of Audio-visual entrainment (AVE) have shown this technique to be promising in the treatment of age-related issues common with our senior citizens. AVE is proving to rehabilitate cognitive function in seniors and the best application of AVE may be that as a prophylactic against cognitive decline.

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a...

Background The recently introduced diagnostic label of Mild Cognitive Impairment (MCI) identifies patients with a cognitive decline that is more pronounced than is usual for a person's age and educational level but does not notably interfere with activities of daily living (ADL). The natural course of the syndrome is uncertain although MCI sufferers have a higher risk of developing dementia. Objectives To investigate how patients fulfilling MCI criteria experience and cope with their cognitive decline with the secondary aim to derive key themes for a prospective MCI support-group programme. Methods The grounded theory approach. Results Analysis of guided interviews with eight MCI patients revealed four common themes. Changes related to cognitive abilities, mobility, affect, vitality and somatic complaints. Attributions were numerous and concerned aetiologies such as personality traits and overload of information. Consequences were all negative and concerned the patients themselves such as anxiety and loss of self-confidence, others such as feelings of irritation and anger towards others or activities like abandoning leisure activities. Patients applied emotion-oriented, problem-focused and avoidant coping strategies. Conclusion MCI patients encounter stress-inducing practical, social and psychological difficulties. Based on the current preliminary findings, the key themes for an MCI support-group programme should include the provision of information about the syndrome's causes, course, concomitant symptoms, attributions, social consequences, and available treatments. The impact of receiving an MCI label warrants further investigation.

BackgroundThe mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline.The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline.ObjectiveTo examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE.To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE.MethodsLinear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time.Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time.ResultsOrientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE.Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE.ConclusionsThe MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright © 2009 John Wiley & Sons, Ltd.The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright © 2009 John Wiley & Sons, Ltd.

Deciphering the 4 D's: cognitive decline, delirium, depression and dementia -a review Purpose. The purpose of this paper is to assist advanced practice nurses to recognize, identify, and diagnose cognitive change in older adults. Background/rationale. Optimal cognitive function is important for continued independence, and yet changes in cognition are frequently unrecognized among older adults. Cognitive change in older adults can be observed due to age-related cognitive decline, the development of acute confusion (delirium), depression, dementia and/or a combination of these. When the aetiological source for alterations in cognitive function is delirium or depression, the potential for reversibility mandates that the reason for the cognitive change be identified with steps taken to remedy the situation. Also, early recognition of dementia is an important factor in obtaining timely and appropriate care. These conditions can exist concurrently and may fluctuate making deciphering the reason for the cognitive change problematic. Conclusions. It is essential to understand how the 4 'D's' are expressed and to recognize the potential contributing factors to an observable change in cognitive function for diagnosis and treatment. Recommendations for obtaining a person's history are included.

This meta-analysis of 28 data sets (N ¼ 705 older adults, N ¼ 962 younger adults) examined age differences in emotion recognition across four modalities: faces, voices, bodies/contexts, and matching of faces to voices. The results indicate that older adults have increased difficulty recognising at least some of the basic emotions (anger, sadness, fear, disgust, surprise, happiness) in each modality, with some emotions (anger and sadness) and some modalities (face-voice matching) creating particular difficulties. The predominant pattern across all emotions and modalities was of age-related decline with the exception that there was a trend for older adults to be better than young adults at recognising disgusted facial expressions. These age-related changes are examined in the context of three theoretical perspectives-positivity effects, general cognitive decline, and more specific neuropsychological change in the social brain. We argue that the pattern of age-related change observed is most consistent with a neuropsychological model of adult aging stemming from changes in frontal and temporal volume, and/or changes in neurotransmitters. r

This study evaluates transfer from domain-specific, sensorimotor training to cognitive abilities associated with executive function. We examined Individualized Piano Instruction (IPI) as a potential cognitive intervention to mitigate normal age-related cognitive decline in older adults. Thirty-one musically naïve community-dwelling older adults (ages 60-85) were randomly assigned to either the experimental group (n ¼ 16) or control group (n ¼ 15). Neuropsychological assessments were administered at three time points: pre-training, following six months of intervention, and following a three-month delay. The experimental group significantly improved performance on the Trail Making Test and Digit Symbol measures as compared to healthy controls. Results of this study suggest that IPI may serve as an effective cognitive intervention for age-related cognitive decline.

Molecular neuroimaging based on annihilation radiation tomographic (ART) techniques such as positron emission tomography (PET), in conjunction with related biomarkers in plasma and cerebrospinal fluid (CSF), are proving valuable in the early and differential diagnosis of Alzheimer's disease (AD). With the advent of new therapeutic strategies aimed at reducing β-amyloid (Aβ) burden in the brain to potentially prevent or delay functional and irreversible cognitive loss, there is increased interest in developing agents that allow assessment of Aβ burden in vivo. Aβ burden as assessed by molecular imaging matches histopathological reports of Aβ plaque distribution in aging and dementia and appears more accurate than FDG for the diagnosis of AD. Aβ imaging is also a very powerful tool in the differential diagnosis of AD from fronto-temporal dementia (FTD). Although Aβ burden as assessed by PET does not correlate with measures of cognitive decline in AD, it does correlate with memory impairment and rate of memory decline in mild cognitive impairment (MCI) and healthy older subjects. Approximately 30% of asymptomatic controls present cortical 11 C-PiB retention. These observations suggest that Aβ deposition is not part of normal ageing, supporting the hypothesis that Aβ deposition occurs well before the onset of symptoms and is likely to represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis and to better elucidate the role of Aβ deposition in the course of Alzheimer's disease.

A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine.

Early diagnosis of Alzheimer's disease ؒ Executive function ؒ Instrumental activities of daily living ؒ Instrumental functional impairment assessment ؒ Mild cognitive impairment ؒ Cognitive decline Abstract Bac kground: The need to detect early changes in instrumental activities of daily life led us to modify the Disability Assessment for Dementia Scale (DAD) by focusing on executive components of 6 instrumental items (DAD-6). Aim: To evaluate the relevance of the DAD-6 for detecting early impairment in a nondemented population. Methods: The DAD-6 was administered to informants of 84 patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and 55 healthy controls. Results: DAD-6 scores gradually decreased with increasing severity of the cognitive status [18 in healthy controls vs. 15.1 ± 3.2 in MCI versus 9.6 ± 3.5 in MD, p < 0.0001). Receiver-operating characteristic curve analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a sensitivity of 0.83 (95% confidence interval 0.74-0.92) and a specificity of 0.84 (0.71-0.94), and a cut score of 15 to distinguish single-domain MCI from multi-domain MCI with a sensitivity of 0.96 (0.90-0.99) and a specificity of 0.54 (0.33-0.75). Conclusion: The DAD-6 reliably detects early loss of autonomy due to cognitive impairment.

The IQCODE is widely used as a screening test for dementia, particularly where the subject is unable to undergo direct cognitive testing or for screening in populations with low levels of education and literacy. This review draws together research on the psychometric properties and validity of the IQCODE.

Ernest Hemingway is one of the most popular and widely acclaimed American writers of the 20th century. His works and life epitomize the image of the hyper-masculine hero, facing the cruelties of life with 'grace under pressure'. Most of his writings have a quasiautobiographical quality, which allowed many commentators to draw comparisons between his personality and his art. Here, we examine the psychological and physical burdens that hindered Hemingway's life and contributed to his suicide. We first take a look at his early years, and review his psychopathology as an adult. A number of authors have postulated specific diagnoses to explain Hemingway's behavior: borderline personality disorder, bipolar disorder, major depression, multiple head trauma, and alcoholism. The presence of hemochromatosis, an inherited metabolic disorder, has also been suggested. We describe the circumstances of his suicide at 61 as the outcome of accumulated physical deterioration, emotional distress and cognitive decline. Special attention is paid to the war wound he suffered in 1918, which seemed to involve a peculiar altered state of consciousness sometimes called 'near-death experience'. The out-of-body experience, paradoxical analgesia and conviction that dying is 'the easiest thing' seemed to influence his future work. The constant presence of danger, death, and violence in his works, as well as the emphasis on the typical Hemingway 'code hero', can all be traced to particular psychological and neurological disorders, as well as his early brush with death.

To validate the Seven-Minute Screen Neurocognitive Battery (7MS) in an elderly population-based sample to identify dementia using a new scoring method. Five hundred and twenty-seven home-dwelling elderly were assessed with a neurological and neuropsychological exam. The total score of the 7MS was the sum of z scores of its subtests. Dementia was diagnosed according to DSM-IV. The ROC curve and the diagnostic parameters of the 7MS were calculated. The 7MS could be fully applied in 416 cases (78.9%), and 48 were diagnosed as demented independently of the 7MS. The four 7MS subtests correctly classified 97.6% of cases by discriminant analysis; orientation and memory were the most discriminative. Factorial analysis showed a single dimension in the 7MS. The ROC curve area for diagnosis of dementia was 0.996 (95% CI 0.992-1), sensitivity 100%, specificity 95.1%, and diagnostic accuracy 96.8%. All these parameters were higher than those of other cognitive screening tests. Dementia explained...

Background and purpose. The CAMCOG is the second most popular cognitive testing instrument in use by Israeli clinicians. The present study examines the reliability and validity of a Hebrew version of the CAMCOG in a group of dementia suerers in a clinical setting.

To determine whether the diffusion abnormalities in brains with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) correlate with disease severity, we studied 34 AD patients using diffusion tensor MRI. Mean diffusivity and fractional anisotropy (FA) as well as three eigenvalues (lambda1, lambda2, and lambda3) of the diffusion tensor of the posterior cingulate white matter correlated with the Mini-Mental State Examination (MMSE) score. The mean diffusivity and the three eigenvalues showed significant correlation with the MMSE score. On the other hand, no significant correlation was seen between the FA and MMSE score. Our results suggested that mean diffusivity and the eigen-values, but not FA, reflect progression of AD-related histopathlogical changes in the posterior cingulate white matter and may be useful biological indices to monitor AD.

Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Metaanalyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.

This review aims to address issues unique to older adults with anxiety disorders in order to inform potential changes in the DSM-V. Prevalence and symptom expression of anxiety disorders in late life, as well as risk factors, comorbidity, cognitive decline, age of onset, and treatment efficacy for older adults are reviewed. Overall, the current literature suggests: (a) anxiety disorders are common among older age individuals, but less common than in younger adults; (b) overlap exists between anxiety symptoms of younger and older adults, although there are some differences as well as limitations to the assessment of symptoms among older adults; (c) anxiety disorders are highly comorbid with depression in older adults; (d) anxiety disorders are highly comorbid with a number of medical illnesses; (e) associations between cognitive decline and anxiety have been observed; (f) late age of onset is infrequent; and (g) both pharmacotherapy and CBT have demonstrated efficacy for older adults with anxiety. The implications of these findings are discussed and recommendations for the DSM-V are provided, including extending the text section on age-specific features of anxiety disorders in late life and providing information about the complexities of diagnosing anxiety disorders in older adults. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.

In the current article, we provide a critical review of the extant literature that has focused on environmental influences on cognitive and brain plasticity over the adult life span. The review includes both human epidemiological, and human and nonhuman cross-sectional and longitudinal research. We review a number of factors that have been suggested to reduce age-related cognitive decline including both formal and informal education, leisure pursuits, intellectual engagement, and expertise in different skill domains. We also examine the literature on cognitive and physical fitness training. We conclude with a discussion of the gaps in the literature and suggestions for future research.

were compared psychometrically. In this study, 525 community-dwelling participants, aged 65-89, were divided into 2 groups: no cognitive impairment (NCI; n-406) and Alzheimer's disease (n = 119). Both tests yielded comparable reliability estimates. Fewer years of education decreased specificity and increased sensitivity, whereas increasing age primarily decreased specificity. It is concluded that although the 2 tests produce comparable effects, the inclusion of a verbal fluency test would increase the sensitivity of the MMSE. Normative data for the NCI group, stratified for 2 age levels (65-79 and 80-89) and 2 educational levels (0-8 and 9+ years), are presented. Folstein, Folstein, and McHugh (1975) introduced the Mini-Mental State Examination (MMSE) as a brief, objective assessment of cognitive functioning and as a measure of changes in cognitive status. The MMSE usually can be administered in 5

Age-related cognitive decline has been reported by several studies. However, little investigations have dealt with the effect of education on this decline. In the present study, we examined the influence of educational level on visual working memory, evaluated by the Benton Visual Retention Test (BVRT in recognition format) in 829 elderly participants of the PAQUID study. A multivariate linear model suggested that the effect of education on BVRT performance was not mediated by visual discrimination abilities suggesting that it was mainly supported by better executive abilities. Moreover, the analysis of success and error location suggested that subjects with higher educational level use a more exhaustive exploration strategy during the recognition phase than subjects with lower educational level, which permit them to better perform. The ability of high educational level subjects to use more efficient strategies may participate to the Ôcognitive reserveÕ capacity.

This paper reviews recent progress in the diagnosis of Alzheimer's disease (AD) from electroencephalograms (EEG). Three major effects of AD on EEG have been observed: slowing of the EEG, reduced complexity of the EEG signals, and perturbations in EEG synchrony. In recent years, a variety of sophisticated computational approaches has been proposed to detect those subtle perturbations in the EEG of AD patients. The paper first describes methods that try to detect slowing of the EEG. Next the paper deals with several measures for EEG complexity, and explains how those measures have been used to study fluctuations in EEG complexity in AD patients. Then various measures of EEG synchrony are considered in the context of AD diagnosis.

This study investigates the implications of different levels of cognitive decline on functional status in frail older adults. Four cognitive trajectories, including two with catastrophic cognitive decline, were defined in a 3-year study. Participants with complete cognitive and functional status data at baseline, 12 and 36 months of follow-up were included in the study (n = 456). Data were analysed with repeated measures statistics. Substantial functional deterioration over time was observed for the participants with catastrophic cognitive decline. Catastrophic cognitive decline influenced performance in instrumental activities of daily living (IADL) and activities of daily living (ADL) at 12 months, whereas basic physical and mental actions were affected at 36 months. IADL were found to deteriorate more than ADL. The results have implications on planning appropriate geriatric rehabilitation and long-term care program.

Correct lipid homeostasis at the plasma membrane is essential for cell survival and performance. These are critically challenged in the aging brain. Changes in the levels of cholesterol, a major membrane component especially enriched in neurons, accompany the brain aging process. They also occur in neurodegenerative diseases. Understanding the causes and consequences of these changes is a crucial step when trying to delay the cognitive decline, which comes with age, or to design strategies to fight neurodegenerative disorders such as Alzheimer's disease. We here review work that has contributed to this understanding.