Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara L.; Rosene, Douglas L.
The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203
Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc
The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.
D’Angelo, Maria C.; Smith, Victoria M.; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A.; Barense, Morgan D.; Ryan, Jennifer D.
ABSTRACT Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals’ failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878
Thukham-Mee, Wipawee; Wattanathorn, Jintanaporn
The present study aimed to determine acute toxicity, the protective effect, and underlying mechanism of PM52, a combined extract of Cissampelos pareira and Anethum graveolens, against age-related cognitive impairment in animal model of age-related cognitive impairment. PM52 was determined as acute toxicity according to OECD guideline. Male Wistar rats, weighing 180-220 g, were orally given PM52 at doses of 2, 10, and 50 mg/kg at a period of 14 days before and 7 days after the bilateral administration of AF64A via intracerebroventricular route. All animals were assessed according to spatial memory, neuron density, MDA level, the activities of SOD, CAT, GSH-Px, and AChEI effect in hippocampus. It was found that all doses of PM52 could attenuate memory impairment and neurodegeneration in hippocampus. The possible mechanisms might occur via the suppression of AChE and the decreased oxidative stress in hippocampus. Therefore, our data suggest that PM52 may serve as food supplement to protect against age-related cognitive impairment such as mild cognitive impairment (MCI) and early phase of Alzheimer's disease. However, further researches are still essential.
Joly, Marine; Ammersdörfer, Sandra; Schmidtke, Daniel; Zimmermann, Elke
Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research.
Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G
Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.
Wang, Feng; Chen, Hong; Sun, Xiaojiang
At present, the mechanisms underlying cognitive disorders remain unclear. The senescence-accelerated mice (SAM) prone/8 (P8) has been proposed as a useful model for the study of aging, and SAM resistant/1 (R1) is its control as a normal aging strain. The purpose of this study was to investigate choline acetyltransferase (ChAT) expression in SAM brain. The age-related decline of learning and memory ability in P8 mice (4, 8 and 12 months old, n=10 for each group) was proved in Morris water maze test (MWM). After the behavioral test, protein and mRNA levels of ChAT were determined in the cerebral cortex, hippocampus and forebrain by means of immunostaining, Western blotting, and real time quantitative PCR (QPCR). Comparing with 4-month-old P8 and R1, 8- and 12-month-old P8 showed age-related cognitive impairment in MWM test. The latencies of the 4-month-old P8 in a hidden platform trial were significantly shorter, and the retention time was significantly longer than that of the older P8 groups. In addition, significantly low level of ChAT protein was observed in older P8 groups. Comparing with the 4-month-old P8, ChAT mRNA in the 12-month-old P8 declined significantly in all three regions of P8 brain. Pearson correlation test showed that the latencies in the MWM were positively correlated with the level of ChAT in P8. Such phenomenon could not be detected in normal aging R1 mice. These findings suggest that the decrease of ChAT in P8 mice was responsible for the age-related learning and memory impairments in some sense.
Bisaz, Reto; Boadas-Vaello, Pere; Genoux, David; Sandi, Carmen
Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However,…
Jagla, Fedor; Pechanova, Olga
It is known that endothelial dysfunction plays an important role in the development and progression of cardiovascular diseases implicated also in cognitive decline. Experimental studies pointed to the fact that the modification of NO levels via NOS activity may affect the blood pressure level as well as several higher nervous functions—for example, learning and memory. There are emerging evidences from in vitro and animal studies suggesting that polyphenols may potentially have a protective effect on the development of neurodegenerative diseases and may improve cognitive function as well as positively affecting the blood pressure regulatory mechanisms. This review accentuates the need for precisely defined clinically controlled studies as well as for use of adequate experimental procedures discriminating between the human higher brain functions and the only overall activation of the brain cortex. The physiological neurocardiovascular interactions are implicated in the increased healthy life span as well. PMID:26180593
Ariel, Robert; Moffat, Scott D
Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual-spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.
Riedel, W J; Jolles, J
A review of recently published studies on the effect of cognition enhancers in non-demented human study participants is presented. The heterogeneity of the therapeutic target, age-associated cognitive decline, can be improved by separately treating groups in whom age-extrinsic factors may underlie cognitive pathology. Standardisation of cognitive assessments is necessary, since many different tests are applied to answer the same question. Modelling cognitive dysfunction, either by pharmacological or nonpharmacological means, in humans is highly recommended since it allows hypotheses to be tested in a clearly operationalised way. Predictive validity of the currently applied models for the clinical situation remains a problem, however. The scopolamine (hyoscine) model has, to a reasonable extent, predictive validity for the cholinergic agents. The results of 67 single-dose studies and 30 multiple-dose studies are summarised. All single-dose studies and 14 multiple-dose studies were carried out in young or elderly human volunteers. In 45 of 81 volunteer studies, models of cognitive dysfunction were employed. The scopolamine model was the most used (n = 21); the other studies induced cognitive dysfunction by means of benzodiazepines (8), hypoxia (7), alcohol (5) and sleep-deprivation (4). The remaining 16 multiple-dose studies were clinical trials of a duration varying between 2 weeks and 1 year (average duration was 14 weeks). In these trials, the effects of cognition enhancers were assessed in elderly people in whom impairment of memory, psychomotor performance or cognitive function was determined. These included age-associated memory impairment (AAMI) and age-associated cognitive decline (AACD). There were many studies in which the cognition enhancing properties of substances in humans were reliably demonstrated. The cognition enhancing properties of substances that are widely used, such as caffeine, nicotine and vitamins, may already be active against AACD. New
Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim
Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086
Yamazaki, Daisuke; Horiuchi, Junjiro; Ueno, Kohei; Ueno, Taro; Saeki, Shinjiro; Matsuno, Motomi; Naganos, Shintaro; Miyashita, Tomoyuki; Hirano, Yukinori; Nishikawa, Hiroyuki; Taoka, Masato; Yamauchi, Yoshio; Isobe, Toshiaki; Honda, Yoshiko; Kodama, Tohru; Masuda, Tomoko; Saitoe, Minoru
Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.
Salthouse, Timothy A.
There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…
Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra
Neurological disorders (Alzheimer’s disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer’s disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer’s disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer’s disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision
Freeman, Willard M.; VanGuilder, Heather D.; Bennett, Colleen; Sonntag, William E.
Declining cognitive performance is associated with increasing age, even in the absence of overt pathological processes. We and others have reported that declining cognitive performance is associated with age-related changes in brain glucose utilization, long-term potentiation and paired-pulse facilitation, protein expression, neurotransmitter levels, and trophic factors. However, it is unclear whether these changes are causes or symptoms of the underlying alterations in dendritic and synaptic morphology that occur with age. In this study, we examined the hippocampal proteome for age- and cognition-associated changes in behaviorally stratified young and old rats, using 2-DIGE and MS/MS-MS. Comparison of old cognitively intact with old cognitively impaired animals revealed additional changes that would not have been detected otherwise. Interestingly, not all age-related changes in protein expression were associated with cognitive decline, and distinct differences in protein expression were found when comparing old cognitively intact with old cognitively impaired rats. A large number of protein changes with age were related to the glycolysis/gluconeogenesis pathway. In total, the proteomic changes suggest that age-related alterations act synergistically with other perturbations to result in cognitive decline. This study also demonstrates the importance of examining behaviorally-defined animals in proteomic studies, as comparison of young to old animals regardless of behavioral performance would have failed to detect many cognitive impairment-specific protein expression changes evident when behavioral stratification data was used. PMID:19135133
Salthouse, Timothy A.
There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure, and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and DTI measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerned with measurement and methodology that may lead to stronger conclusions in the future. PMID:21463028
Tsai, Sheng-Feng; Chen, Pei-Chun; Calkins, Marcus J.; Wu, Shih-Ying; Kuo, Yu-Min
Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. PMID:27047373
Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype
Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.
Bizon, J L; Lee, H J; Gallagher, M
Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.
Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.
The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503
Dichgans, Martin; Leys, Didier
Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.
Bañuelos, Cristina; Beas, B Sofia; McQuail, Joseph A; Gilbert, Ryan J; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L
Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions.
Bañuelos, Cristina; Beas, B. Sofia; McQuail, Joseph A.; Gilbert, Ryan J.; Frazier, Charles J.; Setlow, Barry
Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions. PMID:24599447
Salthouse, Timothy A.
There has recently been a great deal of interest in cognitive interventions, particularly when applied in older adults with the goal of slowing or reversing age-related cognitive decline. Although seldom directly investigated, one of the fundamental questions concerning interventions is whether the intervention alters the rate of cognitive change, or affects the level of certain cognitive measures with no effect on the trajectory of change. This question was investigated with a very simple intervention consisting of the performance of three versions (treatment) or one version (control) of the relevant cognitive tests at an initial occasion. Participants were retested at intervals ranging from less than 1 to 12 years, which allowed rates of change to be examined in the control and treatment groups. Although the intervention can be considered modest, participants in the treatment group had about .25 standard deviations less negative cognitive change over an interval of approximately three years than those in the control group, which is comparable to effect sizes reported with more intensive interventions. However, there were no interactions of the intervention with length of the interval between occasions, and thus there was no evidence that the intervention affected the course of age-related cognitive decline. PMID:26478640
Meyers, Emily A.; Gobeske, Kevin T.; Bond, Allison M.; Jarrett, Jennifer C.; Peng, Chian-Yu; Kessler, John A.
Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. PMID:26827654
Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L
Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.
Maillet, David; Schacter, Daniel L.
The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes. PMID:26617263
Mishra, Jyoti; Gazzaley, Adam
Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual’s neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029
Mizoguchi, K; Shoji, H; Tanaka, Y; Tabira, T
Aging is thought to impair prefrontal cortical (PFC) structure-sensitive cognitive functions and flexibility, such as working memory and reversal learning. A traditional Japanese medicine, yokukansan (YKS), is frequently used to treat age-related neurodegenerative disorders such as Alzheimer's disease in Japan, but its pharmacological properties have not been elucidated. The present study was designed to examine whether YKS improves age-related cognitive deficits using aged rats. YKS was administered to 21-month-old rats for 3 months. The ability to learn initially a reward rule for a T-maze discrimination task (initial learning) was examined in young control (4-month-old), aged control (24-month-old) and YKS-treated aged (24-month-old) rats. Subsequently, working memory and reversal learning were examined in delayed alternation and reversal discrimination T-maze tasks, respectively. Locomotor activity was also measured in new environments. Although performance accuracy in the initial learning procedure did not differ among any experimental groups, accuracy in the delayed alternation task was significantly decreased in aged rats compared to young rats. Aged rats also showed significant decreases in accuracy in the reversal discrimination task. YKS treatment significantly ameliorated the age-related decreases in accuracy in the delayed alternation and reversal discrimination tasks. The ameliorative effects of YKS on impaired delayed alternation performance were reduced by intracranial infusions of a dopamine D1 receptor antagonist, SCH 23390, into the prelimbic cortical region of the PFC, and the YKS effects on impaired reversal learning were done by the infusions into the orbitofrontal cortex (OFC). Locomotor activity did not change in any experimental group. Thus, YKS ameliorated age-related impairments of working memory and reversal learning, which might be mediated by a dopaminergic mechanism in the PFC structure. These investigations provide information
Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.
Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…
Ryan, Lee; Walther, Katrin; Bendlin, Barbara B.; Lue, Lih-Fen; Walker, Douglas G.; Glisky, Elizabeth L.
While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52–92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 non-carriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions – frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter – and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers, but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier
Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.
With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182
Gard, Tim; Hölzel, Britta K; Lazar, Sara W
With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.
Lee, Kyoung Othelia; Brennan, Mark
Narrative data from two earlier studies of adaptation to age-related visual impairment were examined for constellations of stressors and coping styles. In the course of previous qualitative analyses, the researchers identified stress and coping codes according to behavioral, psychological, and social domains using a grounded theory approach. In…
Raj, Towfique; Chibnik, Lori B.; McCabe, Cristin; Wong, Andus; Replogle, Joseph M.; Yu, Lei; Gao, Sujuan; Unverzagt, Frederick W.; Stranger, Barbara; Murrell, Jill; Barnes, Lisa; Hendrie, Hugh C.; Foroud, Tatiana; Krichevsky, Anna; Bennett, David A.; Hall, Kathleen S.; Evans, Denis A.
Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD. PMID:28078323
Morris, Ken A; Chang, Qing; Mohler, Eric G; Gold, Paul E
Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity.
Barry, David M.; Ettenhofer, Mark L.
It was hypothesized that risk for age-related impairment in attention would be greater among those with remote history of mild TBI than individuals without history of head injury. Twenty-seven adults with remote history of mild TBI and a well-matched comparison group of 54 uninjured controls completed a computerized test of visual attention while saccadic and manual response times were recorded. Within the mild TBI group only, older age was associated with slower saccadic responses and poorer saccadic inhibition. Saccadic slowing was mitigated in situations where the timing and location of attention targets was fully predictable. Mild TBI was not associated with age-related increases in risk for neuropsychological impairment or neurobehavioral symptoms. These results provide preliminary evidence that risk for age-related impairment in visual attention may be higher among those with a history of mild TBI. Saccadic measures may provide enhanced sensitivity to this subtle form of cognitive impairment. PMID:28166259
Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C
Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation.
Baierle, Marília; Charão, Mariele F.; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C.; Rocha, Rafael C. C.; Saint’Pierre, Tatiana D.; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Ávila, Daiana S.; Gioda, Adriana; Garcia, Solange C.
Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536
Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034
Borrás Blasco, Consuelo; Viña Ribes, José
Brain ageing is produced by various morphological, biochemical, metabolic and circulatory changes, which are reflected in functional changes, whose impact depends on the presence or absence of cognitive impairment. Because of brain plasticity, together with redundancy of the distinct cerebral circuits, age- related deterioration of the brain at various levels does not always translate into loss of brain function. However, when the damage exceeds certain thresholds, there is age-related cognitive impairment, which increases the risk of developing various neurodegenerative diseases such as Alzheimer disease. Genetics, together with lifestyle, diet, and environmental factors, etc, can trigger the development of these diseases, which provoke cognitive impairment. This article discusses the most important age-related changes in the brain, as well as the pathophysiological foundations of cognitive impairment.
Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George
Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…
To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...
Zelanti, Pierre S.; Droit-Volet, Sylvie
The current study investigated how the development of cognitive abilities explains the age-related changes in temporal judgment over short and long duration ranges from 0.5 to 30 s. Children (5- and 9-year-olds) as well as adults were given a temporal bisection task with four different duration ranges: a duration range shorter than 1 s, two…
Yang, Chao-Hui; Schrepfer, Thomas; Schacht, Jochen
Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise. PMID:26283913
Annoni, Jean-Marie; Chouiter, Leila; Démonet, Jean-François
The actual field of dementia encompasses also the pre-symptomatic phase, which may evolve for decades. Early detection and appropriate diagnosis decrease patient's and family's anxiety, improve patient's global care and allow better legal patient's protection. General Practitioners have at hand several available tools to screen a neurocognitive disorder, with up to 80% of sensitivity and specificity, to complete their clinical evaluation. An accurate diagnosis requires then a complete medical, neurological neuropsychological and neuroradiological evaluation in a Memory Clinic. Other investigations, such as functional cerebral imagery and spinal tap can be critical in unusual situations. Despite mood improvement after diagnostic announcement, increased suicidal risk in the 3 first months should be screened.
De Tata, Vincenzo
The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions. PMID:25232350
Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.
Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310
Antoniou, Mark; Gunasekera, Geshri M; Wong, Patrick C M
Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline-Alzheimer's disease and other dementias-hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis.
Matsumoto, Yukihisa; Matsumoto, Chihiro S.; Takahashi, Toshihumi; Mizunami, Makoto
Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes. PMID:27616985
Sugiura, Saiko; Ueda, Hiromi; Nakashima, Tsutomu
Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed. PMID:25140308
Kennedy, Kristen M.; Rodrigue, Karen M.; Head, Denise; Gunning-Dixon, Faith; Raz, Naftali
Our objectives were to assess age differences in perceptual repetition priming and perceptual skill learning, and to determine whether they are mediated by cognitive resources and regional cerebral volume differences. Fragmented picture identification paradigm allows the study of both priming and learning within the same task. We presented this task to 169 adults (ages 18–80), assessed working memory and fluid intelligence, and measured brain volumes of regions that were deemed relevant to those cognitive skills. The data were analyzed within a hierarchical path modeling framework. In addition to finding age-related decrease in both perceptual priming and learning, we observed several dissociations with regards to their neural and cognitive mediators. Larger visual cortex volume was associated with greater repetition priming, but not perceptual skill learning, and neither process depended upon hippocampal volume. In contrast, the volumes of the prefrontal gray and white matter were differentially related to both processes via direct and indirect effects of cognitive resources. The results indicate that age-related differences in perceptual priming and skill learning have dissociable cognitive and neural correlates. PMID:19586211
Corden, D M; Lippold, O C
1. The rectified and averaged electromyogram (EMG) was recorded from the first dorsal interosseous muscle (FDI) in normal male and female human subjects, ranging in age from 18 to 67 yr. It was elicited by a brief stretch, given to the outstretched forefinger. 2. The responses to stretch consisted of components W30, the monosynaptic stretch reflex and W60, which is likely to arise in the skin and nonmuscular structures. The figures 30 and 60 refer to the mean latencies, in milliseconds, of the respective waveforms (W). 3. For a group of subjects > 30 yr of age, W30 was significantly smaller than in a group under this age. The size of W60 was not related to age and the W30/W60 ratio was < 0.45 in the older subjects. In the younger group, the ratio was always above 0.5. 4. The fact that the age-related reflex impairment affects only W30 and not W60, indicates that central processing in the motor neuron pool is unlikely to be the mechanism involved in the impairment. 5. Control experiments show that changes in frictional resistance in muscles, joints, and tendons with age, are not large enough to account for these results. 6. Neuromuscular block did not occur in these experiments and could not be implicated in the impaired reflex sensitivity.
Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia
Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level.
Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee
To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.
Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee
To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988
Mager, Ralph; Bullinger, Alex H; Brand, Serge; Schmidlin, Maria; Schärli, Heinz; Müller-Spahn, Franz; Störmer, Robert; Falkenstein, Michael
Cognitive tasks involving conflicting stimuli and responses are associated with an early age-related decline in performance. Conflict and conflict-induced interference can be stimulus- or response-related. In classical stimulus-response compatibility tasks, such as the Stroop task, the event-related potential (ERP) usually reveals a greater negativity on incongruent versus congruent trials which has often been linked with conflict processing. However, it is unclear whether this negativity is related to stimulus- or response-related conflict, thus rendering the meaning of age-related changes inconclusive. In the present study, a modified Stroop task was used to focus on stimulus-related interference processes while excluding response-related interference. Since we intended to study work-relevant effects ERPs and performance were determined in young (about 30 years old) and middle-aged (about 50 years old) healthy subjects (total n=80). In the ERP, a broad negativity developed after incongruent versus congruent stimuli between 350 and 650 ms. An age-related increase of the latency and amplitude of this negativity was observed. These results indicate age-related alterations in the processing of conflicting stimuli already in middle age.
Fransen, Erik; Bonneux, Sarah; Corneveaux, Jason J; Schrauwen, Isabelle; Di Berardino, Federica; White, Cory H; Ohmen, Jeffrey D; Van de Heyning, Paul; Ambrosetti, Umberto; Huentelman, Matthew J; Van Camp, Guy; Friedman, Rick A
We performed a genome-wide association study (GWAS) to identify the genes responsible for age-related hearing impairment (ARHI), the most common form of hearing impairment in the elderly. Analysis of common variants, with and without adjustment for stratification and environmental covariates, rare variants and interactions, as well as gene-set enrichment analysis, showed no variants with genome-wide significance. No evidence for replication of any previously reported genes was found. A study of the genetic architecture indicates for the first time that ARHI is highly polygenic in nature, with probably no major genes involved. The phenotype depends on the aggregated effect of a large number of SNPs, of which the individual effects are undetectable in a modestly powered GWAS. We estimated that 22% of the variance in our data set can be explained by the collective effect of all genotyped SNPs. A score analysis showed a modest enrichment in causative SNPs among the SNPs with a P-value below 0.01. PMID:24939585
Fogel, Stuart M; Albouy, Genevieve; Vien, Catherine; Popovicci, Romana; King, Bradley R; Hoge, Rick; Jbabdi, Saad; Benali, Habib; Karni, Avi; Maquet, Pierre; Carrier, Julie; Doyon, Julien
Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network.
Aarsland, Dag; Taylor, John-Paul; Weintraub, Daniel
Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson’s disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment. PMID:24757113
Puccioni, Olga; Vallesi, Antonino
Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595
Mertes, Christine; Wascher, Edmund; Schneider, Daniel
The effect of healthy aging on cognitive control of irrelevant visual information was investigated by using event-related potentials. Participants performed a spatial cuing task where an irrelevant color cue that was either contingent (color search) or noncontingent (shape search) on the attentional set was presented before a target with different stimulus-onset asynchronies. In the contingent condition, attentional capture appeared independent of age and persisted over the stimulus-onset asynchronies but was markedly pronounced for elderly people. Accordingly, event-related potential analyses revealed that both older and younger adults initially selected the irrelevant cue when it was contingent on the attentional set and transferred spatial cue information into working memory. However, only younger adults revealed inhibitory mechanisms to compensate for attentional capture. It is proposed that this age-related lack of reactive inhibition leads to stickiness in visual processing whenever information is contingent on the attentional set, unveiling older adults' "Achilles' heel" in cognitive control.
Saitoe, Minoru; Horiuchi, Junjiro; Tamura, Takuya; Ito, Naomi
Understanding the molecular mechanisms underlying age-related memory impairment (AMI) is important not only from a scientific viewpoint but also for the development of therapeutics that may eventually lead to the development of drugs to combat memory loss. AMI has been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetics to test this hypothesis have not been performed previously, due, in part, to the long lifespan of animal models. Using Drosophila, the first extensive behavioral-genetic characterization of AMI has been carried out. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory (STM), middle-term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM). Significantly, AMI results from the specific decay of only one memory component, amnesiac-dependent MTM, and not other components. Since amnesiac encodes peptides that enhance adenylyl cyclase activity, these studies suggest the importance of the cAMP signaling pathway in AMI in Drosophila, a finding consistent with several models of AMI in mammals. Although many advances have been made in the study of pathways involved in aging, much remains to be elucidated on how these pathways affect memory formation to cause AMI. Due to its short lifespan, powerful genetics, and well-characterized and conserved pathways involved in memory and lifespan, Drosophila will be a useful model system for studying the molecular mechanisms underlying this process.
Edmonds, Caroline J.; Isaacs, Elizabeth B.; Visscher, Peter M.; Rogers, Mary; Lanigan, Julie; Singhal, Atul; Lucas, Alan; Gringras, Paul; Denton, Jane; Deary, Ian J.
We studied the age-related differences in inspection time and multiple cognitive domains in a group of monozygotic (MZ) and dizygotic (DZ) twins aged 7 to 17 years. Data from 111 twin pairs and 19 singleton siblings were included. We found clear age-related trends towards more efficient visual information processing in older participants. There…
Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C
The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain.
McDonnell, Michelle N; Bryan, Janet; Smith, Ashleigh E; Esterman, Adrian J
The assessment of cognitive function is often neglected following stroke, with no consensus on the optimal method to assess poststroke cognition. We evaluated the ability of a brief protocol to detect cognitive impairment in community-dwelling people with chronic stroke compared to healthy controls and its ability to detect changes in cognition in stroke participants undergoing an exercise intervention. Four tests of cognition were able to detect differences between the groups in the domains of executive function, memory, and information-processing speed. Stroke survivors undergoing exercise over a 5-month period showed significantly improved memory and speed of information processing. Results suggest that exercise may have the potential to improve cognition in long-term stroke survivors and that these tests are sensitive measures of poststroke cognition.
Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan
Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…
... noticeable and measurable decline in cognitive abilities, including memory and thinking skills. A person with MCI is ... independent function. People with MCI, especially MCI involving memory problems, are more likely to develop Alzheimerâ€™s disease ...
Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C
We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors.
Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice. PMID:28058128
Yang, Yang; Tang, Bei-Sha; Guo, Ji-Feng
Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice.
Van Laer, Lut; Huyghe, Jeroen R; Hannula, Samuli; Van Eyken, Els; Stephan, Dietrich A; Mäki-Torkko, Elina; Aikio, Pekka; Fransen, Erik; Lysholm-Bernacchi, Alana; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy
This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 x 10(-7)), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.
Van Laer, Lut; Huyghe, Jeroen R; Hannula, Samuli; Van Eyken, Els; Stephan, Dietrich A; Mäki-Torkko, Elina; Aikio, Pekka; Fransen, Erik; Lysholm-Bernacchi, Alana; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy
This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 × 10−7), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene. PMID:20068591
Jefferis, Joanna M; Mosimann, Urs P; Clarke, Michael P
Acquired cataract and cognitive impairment are both common age related problems, and ophthalmologists are increasingly likely to encounter patients who have both. Dementia types which display early visuo-perceptual impairment may present first to ophthalmology services. When these patients have coexisting cataract it may be difficult to distinguish visual complaints due to cataract from those due to dementia. The interaction between visual impairment due to cataract, and neurodegenerative disorders affecting the central visual pathways, is not fully understood. Visual impairment due to cataract may stress impaired attentional mechanisms, and cataract extraction may improve cognitive performance in some patients with early cognitive impairment; however the benefits of cataract surgery in established dementia are less clear. Here we review the literature on this subject and consider the implications for practice. PMID:20807709
Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat
It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105
Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.
Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151
Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.
Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702
Hernandez, Abigail R.; Maurer, Andrew P.; Reasor, Jordan E.; Turner, Sean M.; Barthle, Sarah E.; Johnson, Sarah A.; Burke, Sara N.
Age-associated cognitive decline can reduce an individual’s quality of life. As no single neurobiological deficit can account for the wide spectrum of behavioral impairments observed in old age, it is critical to develop an understanding of how interactions between different brain regions change over the life span. The performance of young and aged animals on behaviors that require the hippocampus and cortical regions to interact, however, has not been well characterized. Specifically, the ability to link a spatial location with specific features of a stimulus, such as object identity, relies on the hippocampus, perirhinal and prefrontal cortices. Although aging is associated with dysfunction in each of these brain regions, behavioral measures of functional change within the hippocampus, perirhinal and prefrontal cortices in individual animals are often not correlated. Thus, how dysfunction of a single brain region within this circuit, such as the hippocampus, impacts behaviors that require communication with the perirhinal and prefrontal cortices remains unknown. To address this question, young and aged rats were tested on the interregion dependent object-place paired association task, as well as a hippocampal-dependent test of spatial reference memory. This particular cohort of aged rats did not show deficits on the hippocampal-dependent task, but were significantly impaired at acquiring object-place associations relative to young. These data suggest that behaviors requiring functional connectivity across different regions of the memory network may be particularly sensitive to aging, and can be used to develop models that will clarify the impact of systems-level dysfunction in the elderly. PMID:26413723
Fein, G; Bachman, L; Fisher, S; Davenport, L
Impaired cognitive functioning in alcoholics is widespread during the first months of detoxification. Between half and two thirds of abstinent alcoholics exhibit cognitive impairments during this period, with residual deficits persisting for years after detoxification in some patients. The most severe deficits have been observed in visuospatial abilities, perceptual-motor integration, abstract reasoning, and new learning. The most significant predictors of cognitive dysfunction in persons recovering from alcoholism are the time elapsed since the last drink and the person's age. Surprisingly, the pattern and duration of a patient's alcohol abuse are relatively weak determinants of neuropsychological impairment during abstinence. Research investigating the hypothesis that cognitive impairments may be related to alcoholic persons resuming drinking has yielded mixed results, but a higher level of neuropsychological functioning is associated with increased rates of completing treatment programs and with greater success in the work environment after discharge from treatment. The possibility of cognitive limitations should be taken into account in planning treatment programs for alcoholism. PMID:2190421
Saedi, Elham; Gheini, Mohammad Reza; Faiz, Firoozeh; Arami, Mohammad Ali
There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings. PMID:27660698
Hennebelle, Marie; Plourde, Mélanie; Chouinard-Watkins, Raphaël; Castellano, Christian-Alexandre; Barberger-Gateau, Pascale; Cunnane, Stephen C
Epidemiological studies fairly convincingly suggest that higher intakes of fatty fish and n-3 fatty acids are associated with reduced risk of Alzheimer's disease (AD). DHA in plasma is normally positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, plasma (or brain) DHA is frequently not lower in AD. This review will highlight some metabolic and physiological factors such as ageing and apoE polymorphism that influence DHA homeostasis. Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults. ApoE4 increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults. In conclusion, recent development of new tools such as isotopically labelled DHA to study DHA metabolism in human subjects highlights some promising avenues to evaluate how and why DHA metabolism changes during ageing and AD.
Lemke, Ulrike; Besser, Jana
Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people.
Mitchell, Paul; Bressler, Neil; Doan, Quan V; Dolan, Chantal; Ferreira, Alberto; Osborne, Aaron; Rochtchina, Elena; Danese, Mark; Colman, Shoshana; Wong, Tien Y
Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.
Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc
Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.
Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara
Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging.
Maimaiti, Shaniya; Anderson, Katie L.; DeMoll, Chris; Brewer, Lawrence D.; Rauh, Benjamin A.; Gant, John C.; Blalock, Eric M.; Porter, Nada M.
Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer’s disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca2+-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889
Siman-Tov, Tali; Bosak, Noam; Sprecher, Elliot; Paz, Rotem; Eran, Ayelet; Aharon-Peretz, Judith; Kahn, Itamar
As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life. PMID:28119599
Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan
Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.
Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E.; Csiszar, Anna
Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID:25136000
Howland, Robert H
Drugs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer's disease include acetylcholinesterase inhibitor drugs (tacrine [Cognex®], donepezil [Aricept®], rivastigmine [Exelon®, Exelon Patch®], and galantamine [Reminyl®, Razadyne®]) and glutamate-modulating drugs (memantine [Namenda®]). They do not halt the underlying degenerative process but can slow disease progression. Piracetam is a nonprescription noot ropic drug designated by the FDA as an orphan drug for myoclonic seizures. Clinical trials in a diverse group of patients with age-related dementia or cognitive impairment demonstrated a significant benefit, but the methodology of these studies is poor, and long-term effects are unknown. Other therapies discussed in this article include Ginkgo biloba, a nonprescription natural supplement, and Axona", designated by the FDA as a medical food.
Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof
We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…
Morris, Ken A.; Gold, Paul E.
Epinephrine enhances memory in young adult rats, in part, by increasing blood glucose levels needed to modulate memory. In old rats, epinephrine is deficient at raising blood glucose levels and thus is only moderately effective at enhancing memory. In contrast, systemic glucose injections improve memory in old rats, with resulting memory performance equal to that of young rats. The diminished response of glucose to training in old rats may blunt downstream neurochemical and molecular mechanisms needed to upregulate memory processes. In the first experiment, young adult and old rats were trained on an inhibitory avoidance task with immediate post-training injections of aCSF or glucose into the dorsal hippocampus. Old rats had significant memory impairments compared to young rats 7 days after training. Intrahippocampal injections of glucose reversed age-related deficits, improving memory scores in old rats to values seen in young rats. A second experiment examined age-related changes in activation of the transcription factor CREB, which is widely implicated in memory formation and may act downstream of hormonal and metabolic signals. Activation was assessed in response to training with systemic injections of epinephrine and glucose at doses known to enhance memory. Young adult and old rats were trained on inhibitory avoidance with immediate post-training systemic injections of saline, epinephrine, or glucose. After training, old rats had significant impairments in CREB phosphorylation in area CA1 and the dentate gyrus region of the hippocampus, and in the basolateral and lateral amygdala. Epinephrine and glucose attenuated age-related deficits in CREB phosphorylation, but were more effective in the amygdala and hippocampus, respectively. Together, these results support the view that age-related changes in blood glucose responses to epinephrine contribute to memory impairments, which may be related to alterations in regional patterns of CREB phosphorylation. PMID
Morris, Ken A; Gold, Paul E
Epinephrine enhances memory in young adult rats, in part, by increasing blood glucose levels needed to modulate memory. In old rats, epinephrine is deficient at raising blood glucose levels and thus is only moderately effective at enhancing memory. In contrast, systemic glucose injections improve memory in old rats, with resulting memory performance equal to that of young rats. The diminished response of glucose to training in old rats may blunt downstream neurochemical and molecular mechanisms needed to upregulate memory processes. In the first experiment, young adult and old rats were trained on an inhibitory avoidance task with immediate post-training injections of aCSF or glucose into the dorsal hippocampus. Old rats had significant memory impairments compared to young rats 7 days after training. Intrahippocampal injections of glucose reversed age-related deficits, improving memory scores in old rats to values seen in young rats. A second experiment examined age-related changes in activation of the transcription factor CREB, which is widely implicated in memory formation and may act downstream of hormonal and metabolic signals. Activation was assessed in response to training with systemic injections of epinephrine and glucose at doses known to enhance memory. Young adult and old rats were trained on inhibitory avoidance with immediate post-training systemic injections of saline, epinephrine, or glucose. After training, old rats had significant impairments in CREB phosphorylation in area CA1 and the dentate gyrus region of the hippocampus, and in the basolateral and lateral amygdala. Epinephrine and glucose attenuated age-related deficits in CREB phosphorylation, but were more effective in the amygdala and hippocampus, respectively. Together, these results support the view that age-related changes in blood glucose responses to epinephrine contribute to memory impairments, which may be related to alterations in regional patterns of CREB phosphorylation.
Lovera, Jesus; Kovner, Blake
Cognitive Impairment (CI) is a serious complication of MS, and the domains affected are well established but new affected domains such as theory of mind are still being identified. The evidence that some disease modifying therapies (DMTs) may improve and prevent the development of CI in MS is not solid. Recent studies on the prevalence CI in MS, although not as solid as studies completed prior to DMT introduction, suggest that CI remains a problem even among people on DMTs and even at the very earliest stages of MS. Functional MRI studies and studies using diffusion tractography show that the impact of lesions on cognition depends on the particular cortical networks affected and their plasticity. Cognitive rehabilitation and L-amphetamine appear promising treatments, cholinesterase inhibitors and memantine have failed, and data on Ginkgo and exercise are limited. We need more work to understand and develop treatment for CI in MS. PMID:22791241
Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez
Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…
Hopley, Charles; Carter, Rob; Mitchell, Paul
The purpose of this report was to: (i) outline the potential value of health economic studies into age-related macular degeneration (AMD); (ii) provide an overview of health economic studies pertinent to AMD; and (iii) outline the basic frame work of cost-of-illness studies (a useful first step in applying economic methods). The detection and management of sensory loss in the elderly plays a key role in the Australian Government's Healthy Ageing Strategy. Age-related macular degeneration is currently the leading cause of blindness in elderly Australians. Although a large proportion of AMD cases remain untreatable, the introduction of photo-dynamic therapy provides a relatively expensive and possibly cost-effective innovation for others. Antioxidant therapy has also been proven effective in reducing progression of early to late disease. The discipline of economics can contribute to an understanding of AMD prevention and treatment through: (i) describing the current burden of disease; (ii) predicting the changes in the burden of disease over time, and (iii) evaluating the efficiency of different interventions. Cost-of-illness studies have been performed in many fields of medicine. Little work, however, has been done on describing the economic impact from AMD. A number of different economic evaluation methods can be used in judging the efficiency of possible interventions to reduce the disease burden of AMD. Although complementary in nature, each has specific uses and limitations. Studies of the economic impact of eye diseases are both feasible and necessary for informed health care decision-making.
Lang, Iain A; Scarlett, Alan; Guralnik, Jack M; Depledge, Michael H; Melzer, David; Galloway, Tamara S
Exposure to heavy metals promotes oxidative stress and damage to cellular components, and may accelerate age-related disease and disability. Physical mobility is a validated biomarker of age-related disability and is predictive of hospitalization and mortality. Our study examined associations between selected heavy metals and impaired lower limb mobility in a representative older human population. Data for 1615 adults aged >or=60 yr from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 were used to identify associations between urinary concentrations of 10 metals with self-reported and measured significant walking impairments. Models were adjusted for confounding factors, including smoking. In models adjusted for age, gender, and ethnicity, elevated levels of cadmium, cobalt, and uranium were associated with impairment of the ability to walk a quarter mile. In fully adjusted models, cobalt was the only metal that remained associated: the odds ratio (OR) for reporting walking problems with a 1-unit increase in logged cobalt concentration (mug/L) was 1.43 (95% CI 1.12 to 1.84). Cobalt was also the only metal associated with a significant increased measured time to walk a 20-ft course. In analyses of disease categories to explain the mobility finding, cobalt was associated with physician diagnosed arthritis (1-unit increase OR = 1.22 (95% CI 1.00 to 1.49). Low-level cobalt exposure, assessed through urinary concentrations of this essential heavy metal, may be a risk factor for age-related physical impairments. Independent replication is needed to confirm this association.
Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published. PMID:27688858
O3 is associated with adverse cardiopulmonary health effects in humans and is thought to produce metabolic effects, such as insulin resistance. Recently, we showed that episodic O3 exposure increased insulin levels in aged rats. We hypothesized that O3 exposure could impair gluc...
Raz, Naftali; Lindenberger, Ulman
The extant longitudinal literature consistently supports the notion of age-related declines in human brain volume. In a report on a longitudinal cognitive follow-up with cross-sectional brain measurements, Burgmans and colleagues (2009) claim that the extant studies overestimate brain volume declines, presumably due to inclusion of participants with preclinical cognitive pathology. Moreover, the authors of the article assert that such declines are absent among optimally healthy adults who maintain cognitive stability for several years. In this comment accompanied by reanalysis of previously published data, we argue that these claims are incorrect on logical, methodological, and empirical grounds.
Johnson, Sarah A; Turner, Sean M; Santacroce, Lindsay A; Carty, Katelyn N; Shafiq, Leila; Bizon, Jennifer L; Maurer, Andrew P; Burke, Sara N
The ability to accurately remember distinct episodes is supported by high-level sensory discrimination. Performance on mnemonic similarity tasks, which test high-level discrimination, declines with advancing age in humans and these deficits have been linked to altered activity in hippocampal CA3 and dentate gyrus. Lesion studies in animal models, however, point to the perirhinal cortex as a brain region critical for sensory discriminations that serve memory. Reconciliation of the contributions of different regions within the cortical-hippocampal circuit requires the development of a discrimination paradigm comparable to the human mnemonic similarity task that can be used in rodents. In the present experiments, young and aged rats were cross-characterized on a spatial water maze task and two variants of an object discrimination task: one in which rats incrementally learned which object of a pair was rewarded and different pairs varied in their similarity (Experiment 1), and a second in which rats were tested on their ability to discriminate a learned target object from multiple lure objects with an increasing degree of feature overlap (Experiment 2). In Experiment 1, aged rats required more training than young to correctly discriminate between similar objects. Comparably, in Experiment 2, aged rats were impaired in discriminating a target object from lures when the pair shared more features. Discrimination deficits across experiments were correlated within individual aged rats, though, for the cohort tested, aged rats were not impaired overall in spatial learning and memory. This could suggest discrimination deficits emerging with age precede declines in spatial or episodic memory, an observation that has been made in humans. Findings of robust impairments in object discrimination abilities in the aged rats parallel results from human studies, supporting use of the developed tasks for mechanistic investigation of cortical-hippocampal circuit dysfunction in aging and
Dumke, Breanna R.
Sarcopenia is the age-associated loss of skeletal muscle mass and strength. Recent evidence suggests that an age-associated loss of muscle precursor cell (MPC) functionality contributes to sarcopenia. The objectives of the present study were to examine the influence of activated T cells on MPCs and determine whether an age-related defect in this signaling occurs. MPCs were collected from the gastrocnemius and plantaris of 3-mo-old (young) and 32-mo-old (old) animals. Splenic T cells were harvested using anti-CD3 Dynabead isolation. T cells were activated for 48 h with costimulation of 100 IU/ml interleukin-2 (IL-2) and 5 μg/ml of anti-CD28. Costimulation increased 5-bromo-2′-deoxyuridine incorporation of T cells from 13.4 ± 4.6% in control to 64.8 ± 6.0% in costimulated cells. Additionally, T cell cytokines increased proliferation on MPCs isolated from young muscle by 24.0 ± 5.7%, whereas there was no effect on MPCs isolated from aged muscle. T cell cytokines were also found to be a chemoattractant. T cells were able to promote migration of MPCs isolated from young muscle; however, MPCs isolated from aged muscle did not respond to the T cell-released chemokines. Conversely, whereas T cell-released cytokines did not affect myogenesis of MPCs isolated from young animals, there was a decrease in MPCs isolated from old animals. These data suggest that T cells may play a critical role in mediating MPC function. Furthermore, aging may alter T cell-induced MPC function. These findings have implications for developing strategies aimed at increasing MPC migration and proliferation leading to an improved regenerative capacity of aged skeletal muscle. PMID:21325640
Ramos Cordero, Primitivo; Yubero, Raquel
This article reviews the effect of non-pharmacological therapies in persons with cognitive impairment, especially treatments aimed at brain stimulation and functional maintenance, since both pharmacological and non-pharmacological therapies affecting the cognitive and psychoaffective domains are reviewed in another article in this supplement. The article also discusses the close and reciprocal relationship between cognitive impairment, diet and nutritional status and describes the main nutritional risk factors and protective factors in cognitive decline.
American Psychologist, 2012
Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…
Torres-Sánchez, Irene; Rodríguez-Alzueta, Elisabeth; Cabrera-Martos, Irene; López-Torres, Isabel; Moreno-Ramírez, Maria Paz; Valenza, Marie Carmen
The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD. PMID:25909154
Li, Wei; Huang, Edgar; Gao, Sujuan
Type 1 diabetes mellitus (T1DM) is a major subtype of diabetes and is usually diagnosed at a young age with insulin deficiency. The life expectancy of T1DM patients has increased substantially in comparison with that three decades ago due to the availability of exogenous insulin, though it is still shorter than that of healthy people. However, the relation remains unclear between T1DM and dementia as an aging-related disease. We conducted a systematic review of existing literature on T1DM and cognition impairments by carrying out searches in electronic databases Medline, EMBASE, and Google Scholar. We restricted our review to studies involving only human subjects and excluded studies on type 2 diabetes mellitus or non-classified diabetes. A meta-analysis was first performed on the relationship between T1DM and cognitive changes in youths and adults respectively. Then the review focused on the cognitive complications of T1DM and their relation with the characteristics of T1DM, glycemic control, diabetic complications, comorbidities, and others. First, age at onset, disease duration, and glycemic dysregulation were delineated for their association with cognitive changes. Then diabetic ketoacidosis, angiopathy, and neuropathy were examined as diabetic complications for their involvement in cognitive impairments. Lastly, body mass index and blood pressure were discussed for their relations with the cognitive changes. Future studies are needed to elucidate the pathogenesis of T1DM-related cognitive impairments or dementia.
Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis
Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative, and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus, and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, the engagement of frontal and cingulate regions persisted in the older group as learning continued, whereas it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure.
Bierre, Kirstin L; Lucas, Samuel J E; Guiney, Hayley; Cotter, James D; Machado, Liana
Alongside age-related brain deterioration, cognitive functioning declines, particularly for more demanding tasks. Past research indicates that, to offset this decline, older adults exhibit hemodynamic changes consistent with recruitment of more anterior brain regions. However, the nature of the hemodynamic changes remains unclear. To address this knowledge gap, we used near-infrared spectroscopy in 36 young adults (aged 18-30 years) and 36 older adults (aged 60-72 years) to assess anterior frontal hemodynamic responses to engagement in three cognitive tasks of increasing difficulty. Behavioral results for all three tasks confirmed aging deficits (evidenced by slower reaction times and reduced accuracy rates) that progressively increased with task difficulty. Hemodynamic results showed opposing effects in young versus older adults, with oxygenated and total hemoglobin decreasing in young but increasing in older adults, particularly during the harder tasks. Also, tissue oxygenation increased only in older adults during the harder tasks. Among the older adults only, anterior frontal hemodynamic changes correlated with better cognitive performance, indicating that they were compensatory in nature. These findings provide novel evidence of age-related anterior frontal hemodynamic changes that intensify with cognitive demands and compensate for performance deficits.
Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil
Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.
Basso, Cristina; Limongi, Federica; Siviero, Paola; Romanato, Giovanna; Noale, Marianna; Maggi, Stefania; Battistin, Leontino; Crepaldi, Gaetano
Several clinically-defined cognitive impairment syndromes, with differing diagnostic criteria and nomenclature, have been proposed to describe nondisabling symptomatic cognitive deficits. Incidence and prevalence rates vary as a result of different diagnostic criteria and sampling procedures across studies. The incidence rates of cognitive impairment increase with age; but no consistent data have been reported on the association with family history, age, sex, education, Apo E4 genotype, depression, and other traditional risk factors for dementia. Several studies have suggested that most patients with cognitive impairment clinically defined will progress to Alzheimer Disease (AD), but rates of conversion vary widely among studies. This review summarizes existing definitions and related epidemiological data.
Farr, Susan A.; Yamada, Kelvin A.; Butterfield, D. Allan; Abdul, H. Mohammad; Xu, Lin; Miller, Nicole E.; Banks, William A.; Morley, John E.
Obesity is associated with cognitive impairments. Long-term mechanisms for this association include consequences of hyperglycemia, dyslipidemia, or other factors comprising metabolic syndrome X. We found that hypertriglyceridemia, the main dyslipidemia of metabolic syndrome X, is in part responsible for the leptin resistance seen in obesity. Here we determined whether triglycerides have an immediate and direct effect on cognition. Obese mice showed impaired acquisition in three different cognitive paradigms: the active avoidance T-maze, the Morris water maze, and a food reward lever press. These impairments were not attributable to differences in foot shock sensitivity, swim speed, swimming distance, or voluntary milk consumption. Impaired cognition in obese mice was improved by selectively lowering triglycerides with gemfibrozil. Injection into the brain of the triglyceride triolein, but not of the free fatty acid palmitate, impaired acquisition in normal body weight mice. Triolein or milk (97% of fats are triglycerides), but not skim milk (no triglycerides), impaired maintenance of the N-methyl-d-aspartate component of the hippocampal long-term synaptic potential. Measures of oxidative stress in whole brain were reduced by gemfibrozil. We conclude that triglycerides mediate cognitive impairment as seen in obesity, possibly by impairing maintenance of the N-methyl-d-aspartate component of hippocampal long-term potentiation, and that lowering triglycerides can reverse the cognitive impairment and improve oxidative stress in the brain. PMID:18276751
Ke, Kathleen Melissa
Neovascular age-related macular degeneration (nvAMD) is a chronic, progressive disease of the central retina, and its prevalence is expected to rise with the ageing population. Using a bottom-up approach based on retrospective data, this cross-sectional study estimated average annual direct costs of nvAMD to be £4,047, and average annual indirect costs to be £449. An attempt to measure intangible costs through willingness-to-pay yielded a lower response rate and estimated intangible costs to be 11.5% of monthly income. Direct costs were significantly higher for male participants, for those who have mild or moderate visual impairment in both eyes, and for those who have been diagnosed for a shorter time. The findings of this study suggest that the availability of early diagnosis, effective treatment, support services, and sustained research into the management of nvAMD may reduce the burden of visual impairment caused by nvAMD to affected individuals and the state.
Bernardin, Florent; Maheut-Bosser, Anne; Paille, François
Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914
Yang, Lumeng; Zhang, Jing; Zheng, Kunmu; Shen, Hui; Chen, Xiaochun
In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.
Bosma, H.; van Boxtel, M. P. J.; Ponds, R. W. H. M.; Houx, P. J. H.; Jolles, J.
Longitudinal data from a Dutch study of 708 older adults showed that persons with low educational attainment experienced more decline in information processing speed, memory, and cognitive function. About 42% of the variance was explained by low stimulus or challenge in work. Decline was independent of crystallized intelligence. (Contains 24…
Salthouse, Timothy A.
A major challenge for researchers interested in investigating relations between aging and cognitive functioning is distinguishing influences of aging from other determinants of cognitive performance. For example, cross-sectional comparisons may be distorted because people of different ages were born and grew up in different time periods, and longitudinal comparisons may be distorted because performance on a second occasion is influenced by the experience of performing the tests on the first occasion. One way in which these different types of influences might be investigated is with research designs involving comparisons of people of different ages from the same birth cohorts who are all tested for the first time in different years. Results from several recent studies using these types of designs suggest that the age trends in some cognitive abilities more closely resemble those from cross-sectional comparisons than those from longitudinal comparisons. These findings imply that a major reason for different age trends in longitudinal and cross-sectional comparisons of cognitive functioning is that the prior experience with the tests inflates scores on the second occasion in longitudinal studies. PMID:25382943
Lo Coco, Daniele; Lopez, Gianluca; Corrao, Salvatore
We reviewed current knowledge about the interaction between stroke and vascular risk factors and the development of cognitive impairment and dementia. Stroke is increasingly recognized as an important cause of cognitive problems and has been implicated in the development of both Alzheimer’s disease and vascular dementia. The prevalence of cognitive impairment after stroke is high, and their combined effects significantly increase the cost of care and health resource utilization, with reflections on hospital readmissions and increased mortality rates. There is also substantial evidence that vascular risk factors (such as hypertension, diabetes, obesity, dyslipidemia, and tobacco smoking) are independently associated with an increased risk of cognitive decline and dementia. Thus, a successful management of these factors, as well as optimal acute stroke management, might have a great impact on the development of cognitive impairment. Notwithstanding, the pathological link between cognitive impairment, stroke, and vascular risk factors is complex and still partially unclear so that further studies are needed to better elucidate the boundaries of this relationship. Many specific pharmacological treatments, including anticholinergic drugs and antihypertensive medications, and nonpharmacological approaches, such as diet, cognitive rehabilitation, and physical activity, have been studied for patients with vascular cognitive impairment, but the optimal care is still far away. Meanwhile, according to the most recent knowledge, optimal stroke care should also include cognitive assessment in the short and long term, and great efforts should be oriented toward a multidisciplinary approach, including quality-of-life assessment and support of caregivers. PMID:27069366
Williamson, Kate A; Hamilton, Andrew; Reynolds, John A; Sipos, Peter; Crocker, Ian; Stringer, Sally E; Alexander, Yvonne M
Aging poses one of the largest risk factors for the development of cardiovascular disease. The increased propensity toward vascular pathology with advancing age maybe explained, in part, by a reduction in the ability of circulating endothelial progenitor cells to contribute to vascular repair and regeneration. Although there is evidence to suggest that colony forming unit-Hill cells and circulating angiogenic cells are subject to age-associated changes that impair their function, the impact of aging on human outgrowth endothelial cell (OEC) function has been less studied. We demonstrate that OECs isolated from cord blood or peripheral blood samples from young and old individuals exhibit different characteristics in terms of their migratory capacity. In addition, age-related structural changes were discovered in OEC heparan sulfate (HS), a glycocalyx component that is essential in many signalling pathways. An age-associated decline in the migratory response of OECs toward a gradient of VEGF significantly correlated with a reduction in the relative percentage of the trisulfated disaccharide, 2-O-sulfated-uronic acid, N, 6-O-sulfated-glucosamine (UA[2S]-GlcNS[6S]), within OEC cell surface HS polysaccharide chains. Furthermore, disruption of cell surface HS reduced the migratory response of peripheral blood-derived OECs isolated from young subjects to levels similar to that observed for OECs from older individuals. Together these findings suggest that aging is associated with alterations in the fine structure of HS on the cell surface of OECs. Such changes may modulate the migration, homing, and engraftment capacity of these repair cells, thereby contributing to the progression of endothelial dysfunction and age-related vascular pathologies.
Lautenschlager, Nicola T; Cox, Kay; Kurz, Alexander F
Regular physical activity undoubtedly has many health benefits for all age groups. In the past decade, researchers and clinicians have begun to focus their attention on whether physical activity also can improve health outcomes of older adults who experience mild cognitive impairment (MCI) or dementia. This ongoing question is gaining relevance in light of the aging of the world population and with it the rise of age-related conditions, such as cognitive impairment. Not surprisingly, physical activity is among the potential protective lifestyle factors mentioned when strategies to delay or prevent dementia are discussed. The first large-scale multidomain intervention trials are under way to put this to the test. This review aims to give an overview of recent trials of physical activity in patients with MCI or dementia.
Stepkina, D A; Zakharov, V V; Yakhno, N N
A total of 88 patients with progression of Parkinson's disease (PD) were studied. Cognitive impairments (CI) in PD were in most cases progressive in nature, predominantly because of increases in the severity of dysregulatory and neurodynamic disorders, impairments to visuospatial functions, and, in some cases, deficits in nominative speech function. A high frequency of transformation of moderate cognitive impairments to dementia was demonstrated over periods of 2-5 years. Predictors of the progression of CI in PD were identified: elderly age, later onset of disease, and the severity of PD. The greatest rate of progression of CI was seen in patients with initially more severe impairments of regulatory and visuospatial functions.
Rhodenizer, Devin; Martin, Ian; Bhandari, Poonam; Pletcher, Scott D; Grotewiel, Mike
Age-related locomotor impairment in humans is important clinically because it is associated with several co-morbidities and increased risk of death. One of the hallmarks of age-related locomotor impairment in humans is a decrease in walking speed with age. Genetically tractable model organisms such as Drosophila are essential for delineating mechanisms underlying age-related locomotor impairment and age-related decreases in locomotor speed. Negative geotaxis, the ability of flies to move vertically when startled, is a common measure of locomotor behavior that declines with age in Drosophila. Toward further developing Drosophila as a model for age-related locomotor impairment, we investigated whether negative geotaxis reflects climbing or a combination of climbing and other behaviors such as flying and jumping. Additionally, we investigated whether locomotor speed in negative geotaxis assays declines with age in flies as found for walking speed in humans. We find that the vast majority of flies climb during negative geotaxis assays and that removal of hind legs, but not wings, impairs the behavior. We also find that climbing speed decreases with age in four wild type genetic backgrounds, in flies housed at different temperatures, and in control and long-lived flies harboring a mutation in OR83b. The decreases in climbing speed correlate with the age-related impairments in the distance climbed. These studies establish negative geotaxis in Drosophila as a climbing behavior that declines with age due to a decrease in climbing speed. Age-related decreases in locomotor speed are common attributes of locomotor senescence in flies and humans.
Gibbons, Christopher H.; Centi, Justin; Vernino, Steven; Freeman, Roy
Background Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody mediated impaired transmission across the autonomic ganglia resulting in severe autonomic failure. Some patients with AAG report cognitive impairment of unclear etiology despite treatment of autonomic symptoms. Objectives To investigate the relationship between orthostatic hypotension, antibody titers and cognitive impairment in patients with AAG. Design Prospective cohort. Setting Academic medical center. Participants Three patients with AAG underwent neuropsychological testing before and after cycles of plasma exchange in both the seated and standing position to determine the effects of orthostatic hypotension and antibody titers on cognition. Main Outcome Measures Patient responses to neuropsychological tests were measured by percent change from baseline in the seated and standing positions pre- and post-plasma exchange to determine the effects of orthostatic hypotension and antibody titers on cognition. Results Orthostatic hypotension and elevated antibody titer were associated independently with neuropsychological impairment (P<0.05), particularly in domains of executive function, sustained attention, and working memory. Cognitive dysfunction improved, even in the seated normotensive position, after plasmapheresis and consequent reduction in antibody levels. Conclusion The data presented in this study demonstrate reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment. PMID:22158721
Arciniegas, David B.; Frey, Kimberly L.; Newman, Jody; Wortzel, Hal S.
Psychiatrists are increasingly called upon to care for individuals with cognitive, emotional, and behavioral disturbances after TBI, especially in settings serving military service personnel and Veterans. In both the early and late post-injury periods, cognitive impairments contribute to disability among persons with TBI and are potentially substantial sources of suffering for persons with TBI and their families. In this article, the differential diagnosis, evaluation, and management of posttraumatic cognitive complaints is reviewed. The importance of pre-treatment evaluation as well as consideration of non-cognitive contributors to cognitive problems and functional limitations is emphasized first. The course of recovery after TBI, framed as a progression through posttraumatic encephalopathy, is reviewed next and used to anchor the evaluation and treatment of posttraumatic cognitive impairments in relation to injury severity as well as time post-injury. Finally, pharmacologic and rehabilitative interventions that may facilitate cognitive and functional recovery at each stage of posttraumatic encephalopathy are presented. PMID:21270968
Daradkeh, Ghazi; Essa, Musthafa M; Al-Adawi, S Samir; Koshy, Roopa P; Al-Asmi, Abdullah; Waly, Mostafa I
The elderly population is increasing worldwide and it has been suggested that senior citizens will continue to constitute the bulk of the population in many countries. Nutritional status of senior citizens are adversely affected by their frailty, chronic condition and declining cognitive functioning. Conversely, malnourished elderly further deteriorate their frailty, chronic disease and cognitive functioning. The aim of this review article is to recognize the importance of nutritional assessment of elderly population particularly those with cognitive impairment. First part is to highlight characteristic cognitive impairment among senior citizens and the second one highlight t he background in which malnutrition is a factor that leads to increased risk of morbidity and mortality in the elderly. This review also highlight salgorithms for safeguarding nutritional status among senior citizen and focuses on importance of nutritional screening, assessment and early intervention for safeguarding further deterioration of elderly who are likely to prone to cognitive impairment.
Stevens, Michael C; Skudlarski, Pawel; Pearlson, Godfrey D; Calhoun, Vince D
A fundamental, yet rarely tested premise of developmental cognitive neuroscience is that changes in brain activity and improvements in behavioral control across adolescent development are related to brain maturational factors that shape a more efficient, highly-interconnected brain in adulthood. We present the first multimodal neuroimaging study to empirically demonstrate that maturation of executive cognitive ability is directly associated with the relationship of white matter development and age-related changes in neural network functional integration. In this study, we identified specific white matter regions whose maturation across adolescence appears to reduce reliance on local processing in brain regions recruited for conscious, deliberate cognitive control in favor of a more widely distributed profile of functionally-integrated brain activity. Greater white matter coherence with age was associated with both increases and decreases in functional connectivity within task-engaged functional circuits. Importantly, these associations between white matter development and brain system functional integration were related to behavioral performance on tests of response inhibition, demonstrating their importance in the maturation of optimal cognitive control.
Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura
The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic’s endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749
Okada, Akinori; Nakamura, Tomohiko; Suzuki, Junichiro; Suzuki, Masashi; Hirayama, Masaaki; Katsuno, Masahisa; Sobue, Gen
Objective Pain and cognitive impairment are important clinical features in patients with Parkinson's disease (PD). Although pain processing is associated with the limbic system, which is also closely linked to the cognitive function, the association between pain and cognitive impairment in PD is still not well understood. The aim of the study was to investigate the association between pain processing and cognitive impairment in patients with PD. Methods Forty-three patients with PD and 22 healthy subjects were studied. Pain-related somatosensory evoked potentials (SEPs) were generated using a thin needle electrode to stimulate epidermal Aδ fibers. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery, and Japanese version of the Montreal Cognitive Assessment (MoCA-J), and their correlation with pain-related SEPs was investigated. Results The N1/P1 amplitude was significantly lower in PD patients than the controls. N1/P1 peak-to-peak amplitudes correlated with the MMSE (r=0.66, p<0.001) and MoCA-J scores (r=0.38, p<0.01) in patients with PD. These amplitudes also strongly correlated with the domains of attention and memory in the MMSE (attention, r=0.52, p<0.001; memory, r=0.40, p<0.01) and MoCA-J (attention, r=0.45, p<0.005; memory, r=0.48, p<0.001), but not in control subjects. Conclusion A good correlation was observed between the decreased amplitudes of pain-related SEPs and an impairment of attention and memory in patients with PD. Our results suggest that pathological abnormalities of the pain pathway are significantly linked to cognitive impairment in PD. PMID:27803403
Saxton, Judith; Morrow, Lisa; Eschman, Amy; Archer, Gretchen; Luther, James; Zuccolotto, Anthony
Many older individuals experience cognitive decline with aging. The causes of cognitive dysfunction range from the devastating effects of Alzheimer’s disease (AD) to treatable causes of dysfunction and the normal mild forgetfulness described by many older individuals. Even mild cognitive dysfunction can impact medication adherence, impair decision making, and affect the ability to drive or work. However, primary care physicians do not routinely screen for cognitive difficulties and many older patients do not report cognitive problems. Identifying cognitive impairment at an office visit would permit earlier referral for diagnostic work-up and treatment. The Computer Assessment of Mild Cognitive Impairment (CAMCI) is a self-administered, user-friendly computer test that scores automatically and can be completed independently in a quiet space, such as a doctor’s examination room. The goal of this study was to compare the sensitivity and specificity of the CAMCI and the Mini Mental State Examination (MMSE) to identify mild cognitive impairment (MCI) in 524 nondemented individuals > 60 years old who completed a comprehensive neuropsychological and clinical assessment together with the CAMCI and MMSE. We hypothesized that the CAMCI would exhibit good sensitivity and specificity and would be superior compared with the MMSE in these measures. The results indicated that the MMSE was relatively insensitive to MCI. In contrast, the CAMCI was highly sensitive (86%) and specific (94%) for the identification of MCI in a population of community-dwelling nondemented elderly individuals. PMID:19332976
Gagnon, K; Baril, A-A; Gagnon, J-F; Fortin, M; Décary, A; Lafond, C; Desautels, A; Montplaisir, J; Gosselin, N
Obstructive sleep apnea (OSA) is characterised by repetitive cessation or reduction of airflow due to upper airway obstructions. These respiratory events lead to chronic sleep fragmentation and intermittent hypoxemia. Several studies have shown that OSA is associated with daytime sleepiness and cognitive dysfunctions, characterized by impairments of attention, episodic memory, working memory, and executive functions. This paper reviews the cognitive profile of adults with OSA and discusses the relative role of altered sleep and hypoxemia in the aetiology of these cognitive deficits. Markers of cognitive dysfunctions such as those measured with waking electroencephalography and neuroimaging are also presented. The effects of continuous positive airway pressure (CPAP) on cognitive functioning and the possibility of permanent brain damage associated with OSA are also discussed. Finally, this paper reviews the evidence suggesting that OSA is a risk factor for developing mild cognitive impairment and dementia in the aging population and stresses the importance of its early diagnosis and treatment.
Arciniegas, David B.; Held, Kerri; Wagner, Peter
Cognitive impairments due to traumatic brain injury (TBI) are substantial sources of morbidity for affected individuals, their family members, and society. Disturbances of attention, memory, and executive functioning are the most common neurocognitive consequences of TBI at all levels of severity. Disturbances of attention and memory are particularly problematic, as disruption of these relatively basic cognitive functions may cause or exacerbate additional disturbances in executive function, communication, and other relatively more complex cognitive functions. Because of the high rate of other physical, neurologic, and psychiatric syndromes following TBI, a thorough neuropsychiatric assessment of the patient is a prerequisite to the prescription of any treatment for impaired cognition. Psychostimulants and other dopaminergically active agents (eg, methylphenidate, dextroamphetamine, amantadine, levodopa/carbidopa, bromocriptine) may modestly improve arousal and speed of information processing, reduce distractibility, and improve some aspects of executive function. Cautious dosing (start-low and go-slow), frequent standardized assessment of effects and side effects, and monitoring for drug-drug interactions are recommended. Cognitive rehabilitation is useful for the treatment of memory impairments following TBI. Cognitive rehabilitation may also be useful for the treatment of impaired attention, interpersonal communication skills, and executive function following TBI. This form of treatment is most useful for patients with mild to moderate cognitive impairments, and may be particularly useful for those who are still relatively functionally independent and motivated to engage in and rehearse these strategies. Psychotherapy (eg, supportive, individual, cognitive-behavioral, group, and family) is an important component of treatment. For patients with medication- and rehabilitation-refractory cognitive impairments, psychotherapy may be needed to assist both patients and
Bilbo, Staci D
There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.
Rao, Mukund G; Holla, Bharath; Varambally, Shivarama; Raveendranathan, Dhanya; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N
Piracetam is a cognitive-enhancing agent that is used for the treatment of cognitive impairments of various etiologies. Little is known about its side effect profile, especially in those with psychiatric illness. We herewith present two cases with cognitive impairment who had contrasting responses to piracetam. One of them with organic amnestic syndrome had significant improvement, whereas the other who had an organic personality change as well as a family history of mental illness had significant worsening of behavioral problems after piracetam was introduced. This report highlights the need for caution in the use of piracetam, especially in those with past or family history of psychiatric illness.
de la Torre, Jack C
This report examines the potential of low level laser therapy (LLLT) to alter brain cell function and neurometabolic pathways using red or near infrared (NIR) wavelengths transcranially for the prevention and treatment of cognitive impairment. Although laser therapy on human tissue has been used for a number of medical conditions since the late 1960s, it is only recently that several clinical studies have shown its value in raising neurometabolic energy levels that can improve cerebral hemodynamics and cognitive abilities in humans. The rationale for this approach, as indicated in this report, is supported by growing evidence that neurodegenerative damage and cognitive impairment during advanced aging is accelerated or triggered by a neuronal energy crisis generated by brain hypoperfusion. We have previously proposed that chronic brain hypoperfusion in the elderly can worsen in the presence of one or more vascular risk factors, including hypertension, cardiac disease, atherosclerosis and diabetes type 2. Although many unanswered questions remain, boosting neurometabolic activity through non-invasive transcranial laser biostimulation of neuronal mitochondria may be a valuable tool in preventing or delaying age-related cognitive decline that can lead to dementia, including its two major subtypes, Alzheimer's and vascular dementia. The technology to achieve significant improvement of cognitive dysfunction using LLLT or variations of this technique is moving fast and may signal a new chapter in the treatment and prevention of neurocognitive disorders.
Lee, Jin San; Shin, Hee Young; Kim, Hee Jin; Jang, Young Kyoung; Jung, Na-Yeon; Lee, Juyoun; Kim, Yeo Jin; Chun, Phillip; Yang, Jin-Ju; Lee, Jong-Min; Kang, Mira; Park, Key-Chung; Na, Duk L; Seo, Sang Won
We investigated the association between self-reported physical exercise and cortical thickness in a large sample of cognitively normal individuals. We also determined whether a combination of physical exercise and education had more protective effects on age-related cortical thinning than either parameter alone. A total of 1,842 participants were included in this analysis. Physical exercise was assessed using a questionnaire regarding intensity, frequency, and duration. Cortical thickness was measured using a surface-based method. Longer duration of exercise (≥1 hr/day), but not intensity or frequency, was associated with increased mean cortical thickness globally (P-value = 0.013) and in the frontal regions (P-value = 0.007). In particular, the association of exercise with cortical thinning had regional specificity in the bilateral dorsolateral prefrontal, precuneus, left postcentral, and inferior parietal regions. The combination of higher exercise level and higher education level showed greater global and frontal mean thickness than either parameter alone. Testing for a trend with the combination of high exercise level and high education level confirmed this finding (P-value = 0.001-0.003). Our findings suggest that combined exercise and education have important implications for brain health, especially considering the paucity of known protective factors for age-related cortical thinning.
Jaszke-Psonka, Magdalena; Piegza, Magdalena; Pudlo, Robert; Piegza, Jacek; Badura-Brzoza, Karina; Leksowska, Aleksandra; Hese, Robert T.; Gorczyca, Piotr W.
Aim To evaluate the incidence and severity of the impairment of selected cognitive functions in patients after sudden cardiac arrest (SCA) in comparison to patients after myocardial infarction without SCA and healthy subjects and to analyze the influence of sociodemographic and clinical parameters and the duration of cardiac arrest on the presence and severity of the described disorders. Material and methods The study group comprised 30 cardiac arrest survivors, the reference group comprised 31 survivors of myocardial infarction without cardiac arrest, and the control group comprised 30 healthy subjects. The Mini-Mental State Examination (MMSE), the Digit Span test from the Wechsler Adult Intelligence Scale, Lauretta Bender’s Visual-Motor Gestalt Test, and the Benton Visual Retention Test (BVRT) were used to assess the presence of cognitive impairment. An original questionnaire developed by the author was used for overall mental state assessment. Results The Bender test demonstrated a significant difference in the presence and severity of visual-motor skills between the study group and the control group, while BVRT and MMSE revealed increased incidence of cognitive impairment in the study group. The Bender and BVRT (D/D)/SS (version D, method D, scaled score) scales indicated cognitive impairment in 53.3% of these patients, while the BVRT (C/A)/SS test indicated cognitive impairment in 40%. For the reference group, the values were 32.3% and 12.9%, respectively. No correlation was found between the severity of cognitive impairment and the duration of cardiac arrest. Conclusions Impairment of visual-motor skills, short-term visual memory, concentration, and visual-motor coordination occurs much more frequently and is more severe in individuals after SCA than in healthy individuals. Impairment of memory trace storage and recall after delay occurs more frequently in patients after SCA than in patients after myocardial infarction without cardiac arrest and in healthy
Woodard, John L; Sugarman, Michael A
Functional magnetic resonance imaging (fMRI) allows for dynamic observation of the neural substrates of cognitive processing, which makes it a valuable tool for studying brain changes that may occur with both normal and pathological aging. fMRI studies have revealed that older adults frequently exhibit a greater magnitude and extent activation of the blood-oxygen-level-dependent signal compared to younger adults. This additional activation may reflect compensatory recruitment associated with functional and structural deterioration of neural resources. Increased activation has also been associated with several risk factors for Alzheimer's disease (AD), including the apolipoprotein ε4 allele. Longitudinal studies have also demonstrated that fMRI may have predictive utility in determining which individuals are at the greatest risk of developing cognitive decline. This chapter will review the results of a number of task-activated fMRI studies of older adults, focusing on both healthy aging and neuropathology associated with AD. We also discuss models that account for cognitive aging processes, including the hemispheric asymmetry reduction in older adults (HAROLD) and scaffolding theory of aging and cognition (STAC) models. Finally, we discuss methodological issues commonly associated with fMRI research in older adults.
Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah
Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID:27354961
Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah
Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.
De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley
The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211
De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley
The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons.
Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan
A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…
Abe, Nobuhito; Mori, Etsuro
Parkinson disease is a progressive neurodegenerative disorder resulting in motor symptoms and cognitive deficits. Neuropsychological studies have suggested that patients with Parkinson disease exhibit a broad range of cognitive deficits even in the early stages of the disease. In this review, we discuss the neuropsychological evidence for cognitive impairment in patients with Parkinson disease, outlining the different domains of cognitive disturbance. First, we review previous findings on executive dysfunction, which is associated with a disruption in frontostriatal circuitry mainly driven by dopaminergic dysmodulation. Executive dysfunction is the core symptom in the cognitive deficits in Parkinson disease. Second, we focus on impairment in different domains of memory function, such as short-term and long-term memory. Third, we discuss the pattern of cognitive deficits in visuospatial ability, ranging from basic perceptual processes to rather complex motor skills. Next, we summarize the profile of cognitive deficits in language, although previous findings are mixed and hence this topic is relatively controversial. Finally, we introduce several recent findings on social cognitive deficits, which is a new area of research that has emerged in the past decade. We also discuss the possible neural mechanisms underlying each domain of cognitive deficits in patients with Parkinson disease.
Wortzel, Hal S.; Arciniegas, David B.
Opinion statement Cognitive impairment is a common consequence of traumatic brain injury (TBI) and a substantial source of disability. Across all levels of TBI severity, attention, processing speed, episodic memory, and executive function are most commonly affected.The differential diagnosis for posttraumatic cognitive impairments is broad, and includes emotional, behavioral, and physical problems as well as substance use disorders, medical conditions, prescribed and self-administered medications, and symptom elaboration. Thorough neuropsychiatric assessment for such problems is a pre-requisite to treatments specifically targeting cognitive impairments.First-line treatments for posttraumatic cognitive impairments are non-pharmacologic, including education, realistic expectation setting, environmental and lifestyle modifications, and cognitive rehabilitation.Pharmacotherapies for posttraumatic cognitive impairments include uncompetitive N-methyl-D-aspartate receptor (NMDA) antagonists, medications that directly or indirectly augment cerebral catecholaminergic or acetylcholinergic function, or agents with combinations of these properties.In the immediate post-injury period, treatment with uncompetitive NMDA receptor antagonists reduces duration of unconsciousness. The mechanism for this effect may involve attenuation of neurotrauma-induced glutamate-mediated excitotoxicity and/or stabilization of glutamate signaling in the injured brain.During the sub-acute or late post-injury periods, medications that augment cerebral acetylcholinergic function may improve declarative memory. Among responders to this treatment, secondary benefits on attention, processing speed, and executive function impairments as well as neuropsychiatric disturbances may be observed. During these post-injury periods, medications that augment cerebral catecholaminergic function may improve hypoarousal, processing speed, attention, and/or executive function as well as comorbid depression or apathy
Yang, Jing; Song, Wei; Wei, Qianqian; Ou, Ruwei; Cao, Bei; Liu, Wanglin; Shao, Na; Shang, Hui-Fang
Backgrounds Studies have reported that non-motor symptoms are an important component of primary dystonia. However, evidence supporting cognitive impairment in primary dystonia is limited and contradictory. Methods We applied the Chinese version of the Addenbrooke’s Cognitive Examination-Revised and the Mini-Mental State Examination (MMSE) to screen for cognitive impairment in patients with primary blepharospasm. In addition, we investigated the relationship between performance on the Addenbrooke’s Cognitive Examination-Revised and quality of life as measured by the Medical Outcomes Study 36-item Short-Form (SF36). Results The study included 68 primary blepharospasm patients and 68 controls matched by age, sex and education. The prevalence of cognitive deficits was 22.0% and 32.3% in primary blepharospasm patients group, as measured by the MMSE and the Addenbrooke’s Cognitive Examination-Revised, respectively. Primary blepharospasm patents had a broad range of cognitive deficits, with the most frequently affected domains being visuospatial function (30.9%) and language (30.9%), followed by memory (27.9%), orientation/attention (26.4%) and verbal fluency (22.0%). Patients with cognitive deficits had lower total SF36 scores, especially in the subdomains of physical functioning, role-physical and social functioning, compared to those without cognitive deficits. Scores on the Addenbrooke’s Cognitive Examination-Revised were significantly correlated with both the SF36 scores and the scores on the subdomains of physical functioning and social functioning. Conclusions Some patients with primary blepharospasm have cognitive deficits. Poor performance on the Addenbrooke’s Cognitive Examination-Revised is related to poorer quality of life. PMID:27526026
Hoffmann, Thomas J.; Keats, Bronya J.; Yoshikawa, Noriko; Risch, Neil
Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3’ of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful
Carr, David B.; Ott, Brian R.
Although automobiles remain the transportation of choice for older adults, late life cognitive impairment and dementia often impair the ability to drive safely. There is, however, no commonly utilized method of assessing dementia severity in relation to driving, no consensus on the assessment of older drivers with cognitive impairment, and no gold standard for determining driving fitness. Yet, clinicians are called upon by patients, their families, other health professionals, and often the Department of Motor Vehicles (DMV) to assess their patients' fitness-to-drive and to make recommendations about driving privileges. Using the case of Mr W, we describe the challenges of driving with cognitive impairment for both the patient and caregiver, summarize the literature on dementia and driving, discuss evidenced-based assessment of fitness-to-drive, and address important ethical and legal issues. We describe the role of physician assessment, referral to neuropsychology, functional screens, dementia severity tools, driving evaluation clinics, and DMV referrals that may assist with evaluation. Finally, we discuss mobility counseling (eg, exploration of transportation alternatives) since health professionals need to address this important issue for older adults who lose the ability to drive. The application of a comprehensive, interdisciplinary approach to the older driver with cognitive impairment will have the best opportunity to enhance our patients' social connectedness and quality of life, while meeting their psychological and medical needs and maintaining personal and public safety. PMID:20424254
Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi
The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700
Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn
Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713
Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn
Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging.
Wiesmann, Maximilian; Kiliaan, Amanda J; Claassen, Jurgen AHR
Hypertension and stroke are highly prevalent risk factors for cognitive impairment and dementia. Alzheimer's disease (AD) and vascular dementia (VaD) are the most common forms of dementia, and both conditions are preceded by a stage of cognitive impairment. Stroke is a major risk factor for the development of vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose to AD. Hypertension is a major risk factor for stroke, thus linking hypertension to VCI and VaD, but hypertension is also an important risk factor for AD. Reducing these two major, but modifiable, risk factors—hypertension and stroke—could be a successful strategy for reducing the public health burden of cognitive impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) and the manipulation of factors involved in the renin–angiotensin system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to reduce the risk of developing hypertension and stroke, thereby reducing dementia risk. This paper will review the research conducted on the relationship between hypertension, stroke, and dementia and also on the impact of LC-n3-FA or antihypertensive treatments on risk factors for VCI, VaD, and AD. PMID:24022624
Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.
Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey . Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593
Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J
Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey . Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.
Grady, Cheryl L.; Protzner, Andrea B.; Kovacevic, Natasa; Strother, Stephen C.; Afshin-Pour, Babak; Wojtowicz, Magda; Anderson, John A.E.; Churchill, Nathan; McIntosh, Anthony R.
We explored the effects of aging on two large scale brain networks, the default mode network (DMN) and the task-positive network (TPN). During fMRI scanning, young and older participants carried out four visual tasks: detection, perceptual matching, attentional cueing, and working memory. Accuracy of performance was roughly matched at 80% across tasks and groups. Modulations of activity across conditions were assessed, as well as functional connectivity of both networks. Younger adults showed a broader engagement of the DMN, and older adults a more extensive engagement of the TPN. Functional connectivity in the DMN was reduced in older adults, whereas the main pattern of TPN connectivity was equivalent in the two groups. Age-specific connectivity also was seen in TPN regions. Increased activity in TPN areas predicted worse accuracy on the tasks, but greater expression of a connectivity pattern associated with a right dorsolateral prefrontal TPN region, seen only in older adults, predicted better performance. These results provide further evidence for age-related differences in the DMN, and new evidence of age differences in the TPN. Increased use of the TPN may reflect greater demand on cognitive control processes in older individuals that may be partially offset by alterations in prefrontal functional connectivity. PMID:19789183
Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.
Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…
Diaper, Danielle C.; Adachi, Yoshitsugu; Sutcliffe, Ben; Humphrey, Dickon M.; Elliott, Christopher J.H.; Stepto, Alan; Ludlow, Zoe N.; Vanden Broeck, Lies; Callaerts, Patrick; Dermaut, Bart; Al-Chalabi, Ammar; Shaw, Christopher E.; Robinson, Iain M.; Hirth, Frank
Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP-43 function, or both, cause disease formation. Here we have systematically compared loss- and gain-of-function of Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function and morphology, motor control, and age-related neuronal survival. Both loss and gain of TBPH severely affect development and result in premature lethality. TBPH dysfunction caused impaired synaptic transmission at the larval neuromuscular junction (NMJ) and in the adult. Tissue-specific knockdown together with electrophysiological recordings at the larval NMJ also revealed that alterations of TBPH function predominantly affect pre-synaptic efficacy, suggesting that impaired pre-synaptic transmission is one of the earliest events in TDP-43-related pathogenesis. Prolonged loss and gain of TBPH in adults resulted in synaptic defects and age-related, progressive degeneration of neurons involved in motor control. Toxic gain of TBPH did not downregulate or mislocalize its own expression, indicating that a dominant-negative effect leads to progressive neurodegeneration also seen with mutational inactivation of TBPH. Together these data suggest that dysfunction of Drosophila TDP-43 triggers a cascade of events leading to loss-of-function phenotypes whereby impaired synaptic transmission results in defective motor behavior and progressive deconstruction of neuronal connections, ultimately causing age-related neurodegeneration. PMID:23307927
Diaper, Danielle C; Adachi, Yoshitsugu; Sutcliffe, Ben; Humphrey, Dickon M; Elliott, Christopher J H; Stepto, Alan; Ludlow, Zoe N; Vanden Broeck, Lies; Callaerts, Patrick; Dermaut, Bart; Al-Chalabi, Ammar; Shaw, Christopher E; Robinson, Iain M; Hirth, Frank
Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial and sporadic forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that either loss or gain of TDP-43 function, or both, cause disease formation. Here we have systematically compared loss- and gain-of-function of Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function and morphology, motor control, and age-related neuronal survival. Both loss and gain of TBPH severely affect development and result in premature lethality. TBPH dysfunction caused impaired synaptic transmission at the larval neuromuscular junction (NMJ) and in the adult. Tissue-specific knockdown together with electrophysiological recordings at the larval NMJ also revealed that alterations of TBPH function predominantly affect pre-synaptic efficacy, suggesting that impaired pre-synaptic transmission is one of the earliest events in TDP-43-related pathogenesis. Prolonged loss and gain of TBPH in adults resulted in synaptic defects and age-related, progressive degeneration of neurons involved in motor control. Toxic gain of TBPH did not downregulate or mislocalize its own expression, indicating that a dominant-negative effect leads to progressive neurodegeneration also seen with mutational inactivation of TBPH. Together these data suggest that dysfunction of Drosophila TDP-43 triggers a cascade of events leading to loss-of-function phenotypes whereby impaired synaptic transmission results in defective motor behavior and progressive deconstruction of neuronal connections, ultimately causing age-related neurodegeneration.
Meramat, A; Rajab, N F; Shahar, S; Sharif, R
Cognitive impairments are often related to aging and micronutrient deficiencies. Various essential micronutrients in the diet are involved in age-altered biological functions such as, zinc, copper, iron, and selenium that play pivotal roles either in maintaining and reinforcing the antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for biological functions. Genomic stability is one of the leading causes of cognitive decline and deficiencies or excess in trace elements are two of the factors relating to it. In this review, we report and discuss the role of micronutrients in cognitive impairment in relation to genomic stability in an aging population. Telomere integrity will also be discussed in relation to aging and cognitive impairment, as well as, the micronutrients related to these events. This review will provide an understanding on how these three aspects can relate with each other and why it is important to keep a homeostasis of micronutrients in relation to healthy aging. Micronutrient deficiencies and aging process can lead to genomic instability.
Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.
Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440
Szirmai, Imre; Kamondi, Anita
The EEG is an indicator of all physiological and neuropsychological activity. The alpha rhythm was considered as a key phenomenon in research of human mentation from the discovery of EEG. Two methods are known for the estimation of cognitive deficit by the use of quantitative EEG (QEEG). The first is based on the hypothesis, that the mean values of the normal EEG from healthy volunteers can be used as reference, and deviation from the normal values of EEG parameters may suggest disease. This kind of "neurometry" was elaborated by R. E. John. The second method assesses event related (ER) transients evoked by somatosensory and mental stimuli. Quantity and localization of signals may refer to the functional state of the cortex. These reactions depend strongly on the test-paradigms. Recognition of the attention-intention cycle disclosed the physiological mechanism of ERD (event related desynchronisation) and ERS (event related synchronisation). In contrast with the classical "stimulus-reaction" model, both perception and voluntary movement are initiated by the brain itself, and not by the environment. Human behavior and conscious actions depend on the intention. QEEG analysis proved that the attention and intention localize in segregate areas of the brain. Both "static" and "dynamic" neurometric methods are able to differentiate the EEG records of demented patients from healthy controls, furthermore some dementias from each other. We conclude that with the help of sophisticated methods of QEEG analysis minimal functional deficit of the electrogenesis can be recognized, which could be helpful in the differential diagnosis Notwithstanding the EEG can not explain the evolution neither the normal or the diseased mental processes. The only "instrument" which is able to approach the human mind is the human cogitation itself with the aids of appropriate tests. The QEEG can be conclusive in the analysis of particular processes of mental activity, such as timing, state of
Dong, Wen; Wang, Rong; Ma, Li-Na; Xu, Bao-Lei; Zhang, Jing-Shuang; Zhao, Zhi-Wei; Wang, Yu-Lan; Zhang, Xu
Recent studies indicated that different caloric intake may influence neuronal function. Excessive caloric intake associated with accelerated aging of the brain and increased the risk of neurodegenerative disorders. And low caloric intake (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms remain poorly understood. In this study, thirty six-week-old male C57/BL male mice were randomly divided into three different dietary groups: normal control (NC) group (fed standard diet), CR group (fed low-caloric diet) and high-calorie (HC) group (fed high-caloric diet). After 10 months, spatial memory ability was determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of proteins involved in autophagy in the hippocampus was determined by immunofluorescence and Western blot. The result of Morris water maze showed that the learning and memory capacity significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining showed cells damaged obviously in the HC group. The expression of mTOR and p62 was increased in the HC group, and decreased in the CR group. The expression of Beclin1, LC3 and cathepsin B was decreased in the HC group, and increased in the CR group. Our findings demonstrate that long-term high caloric intake is a risk factor that can significantly contribute to the development of neurological disease via suppressing autophagy, and CR may prevent age-related learning ability impairment via activating autophagy in mice. PMID:26380026
Objectives This longitudinal investigation addressed whether and how lifetime cumulative adversity and depressive symptoms moderated age-related decline in markers of physical, mental and cognitive health. Method 1,248 older adults (mean age = 62 at Wave 1) who completed the first two waves of the Israeli component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel) reported on exposure to potentially traumatic life events, depressive symptoms, and three outcomes – disability, quality of life and cognitive markers. Results Age was related to greater functional decline in outcome measures across the two waves (i.e., increase in disability and decrease in quality of life and cognitive functioning). This age-related decline became stronger as lifetime adversity increased. A three-way interaction showed that the greatest age-related functional decline in outcome measures was especially salient among those with high level of lifetime adversity and high level of depressive symptoms. Conclusion Lifetime cumulative adversity is associated with a more noticeable process of age-related dysfunction across various markers of health. Although the majority of older adults are resilient to lifetime adversity, prevention and intervention programs should be aimed at mitigating the pronounced senescence observed when adversity accumulated to a large degree, and especially when it is accompanied with high level of distress. PMID:24328416
Butts, Brittany; Gary, Rebecca
Objective To review some of the proposed pathways that increase frailty risk in older persons with heart failure and to discuss tools that may be used to assess for changes in physical and cognitive functioning in this population in order to assist with appropriate and timely intervention. Methods Review of the literature. Results Heart failure is the only cardiovascular disease that is increasing by epidemic proportions, largely due to an aging society and therapeutic advances in disease management. Because heart failure is largely a cardiogeriatric syndrome, age-related syndromes such as frailty and cognitive impairment are common in heart failure patients. Compared with age-matched counterparts, older adults with heart failure 4 to 6 times more likely to be frail or cognitively impaired. The reason for the high prevalence of frailty and cognitive impairment in this population is not well known but may likely reflect the synergistic effects of heart failure and aging, which may heighten vulnerability to stressors and accelerate loss of physiologic reserve. Despite the high prevalence of frailty and cognitive impairment in the heart failure population, these conditions are not routinely screened for in clinical practice settings and guidelines on optimal assessment strategies are lacking. Conclusion Persons with heart failure are at an increased risk for frailty, which may worsen symptoms, impair self-management, and lead to worse heart failure outcomes. Early detection of frailty and cognitive impairment may be an opportunity for intervention and a key strategy for improving clinical outcomes in older adults with heart failure. PMID:26594103
Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando
Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM.
Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando
Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID
Skrobot, Olivia A; Attems, Johannes; Esiri, Margaret; Hortobágyi, Tibor; Ironside, James W; Kalaria, Rajesh N; King, Andrew; Lammie, George A; Mann, David; Neal, James; Ben-Shlomo, Yoav; Kehoe, Patrick G; Love, Seth
There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate
Palop, Jorge J.; Mucke, Lennart
Summary Alzheimer disease (AD) is associated with cognitive decline and increased incidence of seizures. Seizure activity in AD has been widely interpreted as a secondary process resulting from advanced stages of neurodegeneration, perhaps in combination with other age-related factors. However, recent findings in animal models of AD have challenged this notion, raising the possibility that aberrant excitatory neuronal activity represents a primary upstream mechanism that may contribute to cognitive deficits in these models. The following observations suggest that such activity may play a similar role in humans with AD: (1) patients with sporadic AD have an increased incidence of seizures that appears to be independent of disease stage and highest in cases with early onset; (2) seizures are part of the natural history of many pedigrees with autosomal dominant early-onset AD, including those with mutations in presenilin-1, presenilin-2, or the amyloid precursor protein, or with duplications of wild-type amyloid precursor protein; (3) inheritance of the major known genetic risk factor for AD, apolipoprotein E4, is associated with subclinical epileptiform activity in carriers without dementia; and (4) some cases of episodic amnestic wandering and disorientation in AD are associated with epileptiform activity and can be prevented with antiepileptic drugs. Here we review recent experimental data demonstrating that high levels of β-amyloid in the brain can cause epileptiform activity and cognitive deficits in transgenic mouse models of AD. We conclude that β-amyloid peptides may contribute to cognitive decline in AD by eliciting similar aberrant neuronal activity in humans and discuss potential clinical and therapeutic implications of this hypothesis. PMID:19204149
Palop, Jorge J; Mucke, Lennart
Alzheimer disease (AD) is associated with cognitive decline and increased incidence of seizures. Seizure activity in AD has been widely interpreted as a secondary process resulting from advanced stages of neurodegeneration, perhaps in combination with other age-related factors. However, recent findings in animal models of AD have challenged this notion, raising the possibility that aberrant excitatory neuronal activity represents a primary upstream mechanism that may contribute to cognitive deficits in these models. The following observations suggest that such activity may play a similar role in humans with AD: (1) patients with sporadic AD have an increased incidence of seizures that appears to be independent of disease stage and highest in cases with early onset; (2) seizures are part of the natural history of many pedigrees with autosomal dominant early-onset AD, including those with mutations in presenilin-1, presenilin-2, or the amyloid precursor protein, or with duplications of wild-type amyloid precursor protein; (3) inheritance of the major known genetic risk factor for AD, apolipoprotein E4, is associated with subclinical epileptiform activity in carriers without dementia; and (4) some cases of episodic amnestic wandering and disorientation in AD are associated with epileptiform activity and can be prevented with antiepileptic drugs. Here we review recent experimental data demonstrating that high levels of beta-amyloid in the brain can cause epileptiform activity and cognitive deficits in transgenic mouse models of AD. We conclude that beta-amyloid peptides may contribute to cognitive decline in AD by eliciting similar aberrant neuronal activity in humans and discuss potential clinical and therapeutic implications of this hypothesis.
Chamard, Ludivine; Ferreira, Sabrina; Pijoff, Alexa; Silvestre, Manon; Berger, Eric
Objectives. To describe cognitive assessment including social cognition in SPG4 patients. Methods. We reported a series of nine patients with SPG4 mutation with an extensive neuropsychological examination including social cognition assessment. Results. None of our patients presented with mental retardation or dementia. All presented with mild cognitive impairment with a high frequency of attention deficit (100%), executive disorders (89%), and social cognition impairment (78%). An asymptomatic patient for motor skills presented with the same cognitive profile. No correlation was found in this small sample between cognitive impairment and motor impairment, age at disease onset, or disease duration. Conclusions. SPG4 phenotypes share some cognitive features of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Cognitive disorders including executive disorders and social cognition impairment are frequent in SPG4 patients and might sometimes occur before motor disorders. Therefore, cognitive functions including social cognition should be systematically assessed in order to improve the clinical management of this population. PMID:27688599
Navas, Adrián; Papo, David; Boccaletti, Stefano; Del-Pozo, F.; Bajo, Ricardo; Maestú, Fernando; Martínez, J. H.; Gil, Pablo; Sendiña-Nadal, Irene; Buldú, Javier M.
We investigate how hubs of functional brain networks are modified as a result of mild cognitive impairment (MCI), a condition causing a slight but noticeable decline in cognitive abilities, which sometimes precedes the onset of Alzheimer's disease. We used magnetoencephalography (MEG) to investigate the functional brain networks of a group of patients suffering from MCI and a control group of healthy subjects, during the execution of a short-term memory task. Couplings between brain sites were evaluated using synchronization likelihood, from which a network of functional interdependencies was constructed and the centrality, i.e. importance, of their nodes was quantified. The results showed that, with respect to healthy controls, MCI patients were associated with decreases and increases in hub centrality respectively in occipital and central scalp regions, supporting the hypothesis that MCI modifies functional brain network topology, leading to more random structures.
Snyder, Peter J.; Jackson, Colleen E.; Petersen, Ronald C.; Khachaturian, Ara S.; Kaye, Jeffrey; Albert, Marilyn S.; Weintraub, Sandra
The demand for rapidly administered, sensitive, and reliable cognitive assessments that are specifically designed for identifying individuals in the earliest stages of cognitive decline (and to measure subtle change over time) has escalated as the emphasis in Alzheimer’s disease clinical research has shifted from clinical diagnosis and treatment toward the goal of developing presymptomatic neuroprotective therapies. To meet these changing clinical requirements, cognitive measures or tailored batteries of tests must be validated and determined to be fit-for-use for the discrimination between cognitively healthy individuals and persons who are experiencing very subtle cognitive changes that likely signal the emergence of early mild cognitive impairment. We sought to collect and review data systematically from a wide variety of (mostly computer-administered) cognitive measures, all of which are currently marketed or distributed with the claims that these instruments are sensitive and reliable for the early identification of disease or, if untested for this purpose, are promising tools based on other variables. The survey responses for 16 measures/batteries are presented in brief in this review; full survey responses and summary tables are archived and publicly available on the Campaign to Prevent Alzheimer’s Disease by 2020 Web site (http://pad2020.org). A decision tree diagram highlighting critical decision points for selecting measures to meet varying clinical trials requirements has also been provided. Ultimately, the survey questionnaire, framework, and decision guidelines provided in this review should remain as useful aids for the evaluation of any new or updated sets of instruments in the years to come. PMID:21575877
Lam, Yuen Ting
Reactive oxygen species (ROS) regulate bone marrow microenvironment for stem and progenitor cells functions including self-renewal, differentiation, and cell senescence. In response to ischemia, ROS also play a critical role in mediating the mobilization of endothelial progenitor cells (EPCs) from the bone marrow to the sites of ischemic injury, which contributes to postnatal neovascularization. Aging is an unavoidable biological deteriorative process with a progressive decline in physiological functions. It is associated with increased oxidative stress and impaired ischemia-induced neovascularization. This review discusses the roles of ROS in regulating stem and progenitor cell function, highlighting the impact of unbalanced ROS levels on EPC dysfunction and the association with age-related impairment in ischemia-induced neovascularization. Furthermore, it discusses strategies that modulate the oxidative levels of stem and progenitor cells to enhance the therapeutic potential for elderly patients with cardiovascular disease. PMID:26697140
Arranz, Lorena; De Castro, Nuria M; Baeza, Isabel; Maté, Ianire; Viveros, Maria Paz; De la Fuente, Mónica
Age-related changes in immunity have been shown to highly influence morbidity and mortality. The aim of the present work was to study the effects of environmental enrichment (EE) (8-16 weeks) on several functions and oxidative stress parameters of peritoneal leukocytes, previously described as health and longevity markers, in mice at different ages, namely adult (44 +/- 4 weeks), old (69 +/- 4 weeks), and very old (92 +/- 4 weeks). Mortality rates were monitored in control and enriched animals, and effects on survival of long-term exposure to EE until natural death were determined. The results showed that exposure to EE was efficient in improving the function (i.e., macrophage chemotaxis and phagocytosis, lymphocyte chemotaxis and proliferation, natural killer cell activity, interleukin-2 and tumor necrosis factor-alpha levels) and decreasing the oxidative-inflammatory stress (i.e., lowered oxidized glutathione content, xanthine oxidase activity, expression of Toll-like receptors 2 and 4 on CD4 and CD8 cells, and increased reduced glutathione and glutathione peroxidase and catalase activities) of immune cells. These positive effects of EE were especially remarkable in animals at older ages. Importantly, long-term exposure to EE from adult age and until natural death stands out as a useful strategy to extend longevity. Thus, the present work confirms the importance of maintaining active mental and/or physical activity aiming to improve quality of life in terms of immunity, and demonstrates that this active life must be initiated at early stages of the aging process and preserved until death to improve life span.
Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.
Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old) * alcohol consumption (light, moderate) factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long-term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers. PMID:25601835
Shi, Min; Huber, Bertrand R.; Zhang, Jing
Cognitive impairment, including dementia, is commonly seen in those afflicted with Parkinson disease (PD), particularly at advanced disease stages. Pathologically, PD with dementia (PD-D) is most often associated with the presence of cortical Lewy bodies, as is the closely related dementia with Lewy bodies (DLB). Both PD-D and DLB are also frequently complicated by the presence of neurofibrillary tangles and amyloid plaques, features most often attributed to Alzheimer disease. Biomarkers are urgently needed to differentiate among these disease processes and predict dementia in PD as well as monitor responses of patients to new therapies. A few clinical assessments, along with structural and functional neuroimaging, have been utilized in the last few years with some success in this area. Additionally, a number of other strategies have been employed to identify biochemical/molecular biomarkers associated with cognitive impairment and dementia in PD, e.g., targeted analysis of candidate proteins known to be important to PD pathogenesis and progression in cerebrospinal fluid or blood. Finally, interesting results are emerging from preliminary studies with unbiased and high throughput genomic, proteomic and metabolomic techniques. The current findings and perspectives of applying these strategies and techniques are reviewed in this article, together with potential areas of advancement. PMID:20522092
Algarabel, Salvador; Fuentes, Manuel; Escudero, Joaquín; Pitarque, Alfonso; Peset, Vicente; Mazón, José-Francisco; Meléndez, Juan-Carlos
There is no agreement on the pattern of recognition memory deficits characteristic of patients diagnosed with mild cognitive impairment (MCI). Whereas lower performance in recollection is the hallmark of MCI, there is a strong controversy about possible deficits in familiarity estimates when using recognition memory tasks. The aim of this research is to shed light on the pattern of responding in recollection and familiarity in MCI. Five groups of participants were tested. The main participant samples were those formed by two MCI groups differing in age and an Alzheimer's disease group (AD), which were compared with two control groups. Whereas one of the control groups served to assess the performance of the MCI and AD people, the other one, composed of young healthy participants, served the purpose of evaluating the adequacy of the experimental tasks used in the evaluation of the different components of recognition memory. We used an associative recognition task as a direct index of recollection and a choice task on a pair of stimuli, one of which was perceptually similar to those studied in the associative recognition phase, as an index of familiarity. Our results indicate that recollection decreases with age and neurological status, and familiarity remains stable in the elderly control sample but it is deficient in MCI. This research shows that a unique encoding situation generated deficits in recollective and familiarity mechanisms in mild cognitive impaired individuals, providing evidence for the existence of deficits in both retrieval processes in recognition memory in a MCI stage.
Dillon, Carol; Serrano, Cecilia M; Castro, Diego; Leguizamón, Patricio Perez; Heisecke, Silvina L; Taragano, Fernando E
Neuropsychiatric symptoms (NPS) are core features of Alzheimer’s disease and related dementias. On one hand, behavioral symptoms in patients with mild cognitive impairment (MCI) can indicate an increased risk of progressing to dementia. On the other hand, mild behavioral impairment (MBI) in patients who usually have normal cognition indicates an increased risk of developing dementia. Whatever the cause, all dementias carry a high rate of NPI. These symptoms can be observed at any stage of the disease, may fluctuate over its course, are a leading cause of stress and overload for caregivers, and increase rates of hospitalization and early institutionalization for patients with dementia. The clinician should be able to promptly recognize NPI through the use of instruments capable of measuring their frequency and severity to support diagnosis, and to help monitor the treatment of behavioral symptoms. The aims of this review are to describe and update the construct ‘MBI’ and to revise the reported NPS related to prodromal stages of dementia (MCI and MBI) and dementia stages of Alzheimer’s disease and frontotemporal lobar degeneration. PMID:24092982
Barekatain, Majid; Alavirad, Maryam; Tavakoli, Mahgol; Emsaki, Golita; Maracy, Mohammad Reza
Background: The nonamnesic type of mild cognitive impairment (na-MCI) is predementia state with subtle decline incognitive domains except memory. Although cognitive rehabilitation (CR) has been investigated in amnesic type of MCI, we could not find any trial that rehabilitated na-MCI exclusively. We studied the effectiveness of CR on na-MCI. Materials and Methods: This study was a blinded, randomized clinical trial. Individuals with age of 60 years or more, complete self-directedness and diagnosis of na-MCI, based on Neuropsychiatry Unit Cognitive assessment tool, were selected. The 51 patients were randomly assigned into three groups: CR, lifestyle (LS) modification, and the control group (CG). Neuropsychological tests for executive functioning were assessed at the baseline, after the interventions, and 6 months later. Results: The mean score of the “design fluency” test increased significantly in CR, compared to LS and CG (P = 0.007). In “five-point” test, mean score increased significantly in CR (P = 0.03). There was higher mean score of Behavioral Rating Inventory of Executive Function for adults in CR (P = 0.01). Conclusion: Consideration of the MCI subtypes allows us to target specific cognitive domains, such as information processing, for better CR outcome. CR may result in better performance of executive functioning of daily living. PMID:28250778
Crişan, Alexandru F.; Oancea, Cristian; Timar, Bogdan; Fira-Mladinescu, Ovidiu; Crişan, Alexandru; Tudorache, Voicu
Background/Purpose Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with multiple cognitive problems. Montreal Cognitive Assessment test (MoCA) is used to detect cognitive impairment evaluating several areas: visuospatial, memory, attention and fluency. Our study aim was to evaluate the impact of stable COPD and exacerbation (AECOPD) phases on cognitive status using MoCA questionnaire. Methods We enrolled 39 patients (pts), smokers with COPD group D (30 stable and 9 in AECOPD) and 13 healthy subjects (control group), having similar level of education and no significant differences regarding the anthropometric measurements. We analyzed the differences in MoCA score between these three groups and also the correlation between this score and inflammatory markers. Results Patients with AECOPD had a significant (p<0.001) decreased MoCA score (14.6±3.4) compared to stable COPD (20.2±2.4) and controls (24.2±5.8). The differences between groups were more accentuated for the language abstraction and attention (p<0.001) and delayed recall and orientation (p<0.001) sub-topics. No significant variance of score was observed between groups regarding visuospatial and naming score (p = 0.095). The MoCA score was significantly correlated with forced expiratory volume (r = 0.28) and reverse correlated with C-reactive protein (CRP) (r = −0.57), fibrinogen (r = −0.58), erythrocyte sedimentation rate (ESR) (r = −0.55) and with the partial pressure of CO2 (r = −0.47). Conclusions According to this study, COPD significantly decreases the cognitive status in advanced and acute stages of the disease. PMID:25033379
Bush, C.; Kozak, J.; Elmslie, T.
OBJECTIVE: To evaluate the extent and type of screening for cognitive impairment primary care physicians use for their elderly patients, to identify perceived barriers to screening, and to explore whether physicians would be willing to use the clock drawing test as a cognitive screening tool. DESIGN: Mailed questionnaire. SETTING: Primary care practices in the Ottawa-Carleton region. PARTICIPANTS: Family physicians and general practitioners culled from the Yellow Pages and Canadian Medical Directory; 368 of 568 questionnaires were returned for a response rate of 70%. Six respondents had fewer than 30 patients weekly and two responded too late to be included in the analysis; 360 cases were included in the analysis. MAIN OUTCOME MEASURES: Responses to 10 questions on cognitive screening and five on demographics and the nature of respondents' practices. RESULTS: About 80% of respondents reported doing at least one mental status examination during the past year. Only 24% routinely screened patients, although 82% believed screening was needed. Major barriers to cognitive screening were lack of time, risk of offending patients, and possible negative consequences of follow up. Clock drawing was perceived as an acceptable method of screening, if it were proven effective. CONCLUSIONS: Most primary care physicians believe cognitive screening is needed, but few routinely screen their elderly patients. Lack of time is the most important perceived barrier to screening. Primary care physicians are receptive to using the clock drawing test, and, because it is not time-consuming, are less likely to consider lack of time a barrier to testing. The clock test might help bridge the gap between perceived need for screening and actual screening. PMID:9356757
Stapleton, Jill M.; Poirier, Martin P.; Flouris, Andreas D.; Boulay, Pierre; Sigal, Ronald J.; Malcolm, Janine; Kenny, Glen P.
Studies have reported that older females have impaired heat loss responses during work in the heat compared to young females. However, it remains unclear at what level of heat stress these differences occur. Therefore, we examined whole-body heat loss [evaporative (HE) and dry heat loss, via direct calorimetry] and changes in body heat storage (∆Hb, via direct and indirect calorimetry) in 10 young (23±4 years) and 10 older (58±5 years) females matched for body surface area and aerobic fitness (VO2peak) during three 30-min exercise bouts performed at incremental rates of metabolic heat production of 250 (Ex1), 325 (Ex2) and 400 (Ex3) W in the heat (40°C, 15% relative humidity). Exercise bouts were separated by 15 min of recovery. Since dry heat gain was similar between young and older females during exercise (p=0.52) and recovery (p=0.42), differences in whole-body heat loss were solely due to HE. Our results show that older females had a significantly lower HE at the end of Ex2 (young: 383±34 W; older: 343±39 W, p=0.04) and Ex3 (young: 437±36 W; older: 389±29 W, p=0.008), however no difference was measured at the end of Ex1 (p=0.24). Also, the magnitude of difference in the maximal level of HE achieved between the young and older females became greater with increasing heat loads (Ex1=10.2%, Ex2=11.6% and Ex3=12.4%). Furthermore, a significantly greater ∆Hb was measured for all heat loads for the older females (Ex1: 178±44 kJ; Ex2: 151±38 kJ; Ex3: 216±25 kJ, p=0.002) relative to the younger females (Ex1: 127±35 kJ; Ex2: 96±45 kJ; Ex3: 146±46 kJ). In contrast, no differences in HE or ∆Hb were observed during recovery (p>0.05). We show that older habitually active females have an impaired capacity to dissipate heat compared to young females during exercise-induced heat loads of ≥325 W when performed in the heat. PMID:25790024
Hunt, Earl; Hertzog, Christopher
In order to alleviate present and anticipated personnel shortages, the Armed Services will have to move away from the present reliance on young adults as a source of personnel. Questions remain about the effects of age changes in cognition on work performance of older personnel. Changes in cognitive capacities over the adult working years are…
Martins, Isabel Pavão; Maruta, Carolina; Silva, Cláudia; Rodrigues, Pedro; Chester, Catarina; Ginó, Sandra; Freitas, Vanda; Freitas, Sara; Oliveira, António Gouveia
The present study aims to investigate the protective effect of formal education on age-related changes in different cognitive domains with the hypothesis that it may attenuate the rate of decline. Individuals aged 50 years or older attending primary care physicians without known brain disease (431 participants, mostly [60.3%] female with 66.3 [±9.1] years of age and 7.7 [±4.1] years of education, on average), were evaluated with a neuropsychological battery including 28 cognitive measures. Cognitive domains identified by factor analysis were subject to repeated multiple regression analyses to determine the variance explained by age and education controlling for gender, depressive symptoms, and vascular risk factors. The slope of the regression equation was compared between two educational groups with an average of 4 years and 11 years of education, respectively. Factors identified corresponded to processing ability (Factor 1), memory (Factor 2), and acquired knowledge (Factor 3). Although education improved performance in Factors 1 and 3, it did not change the slope of age-related decline in any factor. This study suggests that in culturally heterogeneous groups, small increments in education enhance cognition but do not modify the rate of decline of executive functioning with age. These results contradict some clinical findings and need to be confirmed in longitudinal studies.
Barashkov, Nikolay A; Teryutin, Fedor M; Pshennikova, Vera G; Solovyev, Aisen V; Klarov, Leonid A; Solovyeva, Natalya A; Kozhevnikov, Andrei A; Vasilyeva, Lena M; Fedotova, Elvira E; Pak, Maria V; Lekhanova, Sargylana N; Zakharova, Elena V; Savvinova, Kyunney E; Gotovtsev, Nyurgun N; Rafailo, Adyum M; Luginov, Nikolay V; Alexeev, Anatoliy N; Posukh, Olga L; Dzhemileva, Lilya U; Khusnutdinova, Elza K; Fedorova, Sardana A
Age-Related Hearing Impairment (ARHI) is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene) and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia). This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz) and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females). Moreover, the average hearing thresholds on high frequency (8.0 kHz) in individuals with genotype IVS1+1G>A/wt (both sexes) were significantly worse than in individuals with genotype wt/wt (p<0.05). Age of hearing loss manifestation in individuals with genotype IVS1+1G>A/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003). These findings demonstrate that the single IVS1+1G>A mutation (GJB2) is associated with age-related hearing impairment (ARHI) of the IVS1+1G>A carriers in the Yakuts.
Pshennikova, Vera G.; Solovyev, Aisen V.; Klarov, Leonid A.; Solovyeva, Natalya A.; Kozhevnikov, Andrei A.; Vasilyeva, Lena M.; Fedotova, Elvira E.; Pak, Maria V.; Lekhanova, Sargylana N.; Zakharova, Elena V.; Savvinova, Kyunney E.; Gotovtsev, Nyurgun N.; Rafailo, Adyum M.; Luginov, Nikolay V.; Alexeev, Anatoliy N.; Posukh, Olga L.; Dzhemileva, Lilya U.; Khusnutdinova, Elza K.; Fedorova, Sardana A.
Age-Related Hearing Impairment (ARHI) is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene) and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia). This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz) and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females). Moreover, the average hearing thresholds on high frequency (8.0 kHz) in individuals with genotype IVS1+1G>A/wt (both sexes) were significantly worse than in individuals with genotype wt/wt (p<0.05). Age of hearing loss manifestation in individuals with genotype IVS1+1G>A/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003). These findings demonstrate that the single IVS1+1G>A mutation (GJB2) is associated with age-related hearing impairment (ARHI) of the IVS1+1G>A carriers in the Yakuts. PMID:24959830
Hahn, Changtae; Lee, Chang-Uk; Won, Wang Yeon; Joo, Soo-Hyun
Objective This study aimed to investigate thalamic shape alterations and their relationships with various episodic memory impairments in subjects with amnestic mild cognitive impairment (aMCI). Methods We compared volumes and morphological alterations of the thalamus between aMCI subjects and healthy controls. In addition, we investigated the correlation between thalamic deformations and various memory impairments in aMCI subjects using a comprehensive neuropsychological battery. Results The normalized left thalamic volumes of the aMCI group were significantly smaller than those of the healthy control group (p<0.0001). aMCI subjects exhibited significant thalamic deformations in the left thalamic dorso-medial and antero-medial areas compared with healthy individuals. CERAD-K Word List Memory scores were significantly correlated with the left dorso-medial areas in aMCI subjects. There were no significant correlations between verbal fluency, Boston naming test, constructional praxis, Word List Recognition, and Visuospatial Recall scores and thalamic shape in aMCI subjects. Verbal delayed recall scores were also significantly correlated with the left dorso-medial areas in the aMCI group. Conclusion Structural alterations in the thalamic deformations in the left dorso-medial and antero-medial areas might be core underlying neurobiological mechanisms of thalamic dysfunction related to Word List Memory and delayed verbal recall in individuals with aMCI. PMID:27757128
Weigand, Anne; Fan, Yan; Gärtner, Matti; Feeser, Melanie; Bajbouj, Malek
The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction. PMID:24561917
Ritchie, Stuart J.; Gow, Alan J.; Deary, Ian J.
A well-replicated finding in the psychological literature is the negative correlation between religiosity and intelligence. However, several studies also conclude that one form of religiosity, church attendance, is protective against later-life cognitive decline. No effects of religious belief per se on cognitive decline have been found, potentially due to the restricted measures of belief used in previous studies. Here, we examined the associations between religiosity, intelligence, and cognitive change in a cohort of individuals (initial n = 550) with high-quality measures of religious belief taken at age 83 and multiple cognitive measures taken in childhood and at four waves between age 79 and 90. We found that religious belief, but not attendance, was negatively related to intelligence. The effect size was smaller than in previous studies of younger participants. Longitudinal analyses showed no effect of either religious belief or attendance on cognitive change either from childhood to old age, or across the ninth decade of life. We discuss differences between our cohort and those in previous studies – including in age and location – that may have led to our non-replication of the association between religious attendance and cognitive decline. PMID:25278639
Lorenzo-López, Laura; Millán-Calenti, José C; López-López, Rocío; Diego-Diez, Clara; Laffon, Blanca; Pásaro, Eduardo; Valdiglesias, Vanessa; Maseda, Ana
Our aim was to estimate the prevalence of cognitive impairment in rural and urban elderly populations and to examine the relationship between lifetime occupation and general cognitive performance. A cross-sectional study was carried out covering a representative sample (n = 749) of adults aged ≥65 years. Two categories were created to define the degree of urbanization using a criterion of geographical contiguity in combination with a minimum population threshold: densely populated (urban) areas and intermediate-thinly populated (rural) areas. Occupational histories were ranked by skill level requirements according to the Spanish National Classification of Occupations. Prevalence estimates of cognitive impairment were measured with the Mini-Mental State Examination. Results show that rural residence was not significantly associated with higher risk of cognitive impairment. A protective effect of cognitive demands at work against age-related cognitive decline was observed. However, this effect was not independent of confounder factors, such as age and education. A low overall prevalence of cognitive impairment was observed (6.5%), compared with previous estimates, possibly due to the sample selection in senior centers. Occupation during active life is not an isolated protective factor against cognitive impairment, and it is closely related to educational level. In future geriatric programs, description of both factors should be taken into consideration in screening older adults at increased risk of cognitive impairment and dementia.
Lorenzo-López, Laura; Millán-Calenti, José C.; López-López, Rocío; Diego-Diez, Clara; Laffon, Blanca; Pásaro, Eduardo; Valdiglesias, Vanessa; Maseda, Ana
Our aim was to estimate the prevalence of cognitive impairment in rural and urban elderly populations and to examine the relationship between lifetime occupation and general cognitive performance. A cross-sectional study was carried out covering a representative sample (n = 749) of adults aged ≥65 years. Two categories were created to define the degree of urbanization using a criterion of geographical contiguity in combination with a minimum population threshold: densely populated (urban) areas and intermediate-thinly populated (rural) areas. Occupational histories were ranked by skill level requirements according to the Spanish National Classification of Occupations. Prevalence estimates of cognitive impairment were measured with the Mini-Mental State Examination. Results show that rural residence was not significantly associated with higher risk of cognitive impairment. A protective effect of cognitive demands at work against age-related cognitive decline was observed. However, this effect was not independent of confounder factors, such as age and education. A low overall prevalence of cognitive impairment was observed (6.5%), compared with previous estimates, possibly due to the sample selection in senior centers. Occupation during active life is not an isolated protective factor against cognitive impairment, and it is closely related to educational level. In future geriatric programs, description of both factors should be taken into consideration in screening older adults at increased risk of cognitive impairment and dementia. PMID:28243214
Idrizbegovic, Esma; Bogdanovic, Nenad; Willott, James F; Canlon, Barbara
Aging C57BL/6J (C57) mice (1-30 months old), were used to study calcium-binding protein immunoreactivity (parvalbumin, calbindin and calretinin) in the cochlear nucleus. A quantitative stereological method, the optical fractionator was used to determine the total number of neurons, and the total number of immunostained neurons in the posteroventral- and dorsal cochlear nuclei (PVCN and DCN). A statistically significant age-related decrease of the total number of neurons was found in the PVCN and DCN using Nissl staining. In the DCN, an age-related increase in the total number of parvalbumin-positive neurons was found, while no changes in the total number of calbindin or calretinin positive neurons were demonstrated. In the PVCN, the total number of parvalbumin, calbindin, or calretinin positive neurons remained stable with increasing age. The percentage of parvalbumin, calbindin, and calretinin positive neurons significantly increased in the DCN, and the percentage of parvalbumin and calbindin-positive neurons increased in the PVCN. These findings imply that there is a relative up-regulation of calcium-binding proteins in neurons that had not previously expressed these proteins. This plastic response in the profoundly hearing impaired C57 mouse may be a survival strategy for cochlear nucleus neurons.
Troen, Aron M; Shea-Budgell, Melissa; Shukitt-Hale, Barbara; Smith, Donald E; Selhub, Jacob; Rosenberg, Irwin H
In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We report here that feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies (r = -0.757, P < 0.001), and with plasma total homocysteine (r = -0.631, P = 0.007). Feeding mice a methionine-rich diet produced similar but less pronounced effects. Our findings suggest that cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration. Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline.
Shobin, Eli; Bowley, Michael P; Estrada, Larissa I; Heyworth, Nadine C; Orczykowski, Mary E; Eldridge, Sherri A; Calderazzo, Samantha M; Mortazavi, Farzad; Moore, Tara L; Rosene, Douglas L
While cognitive decline is observed in the normal aging monkey, neurons are not lost with age. Instead, frontal white matter is lost as myelin degenerates and both correlate with age-related cognitive decline. As age-related myelin damage increases, there should be an increase in clearance of damaged myelin by microglial phagocytosis. In this study, brains of behaviorally tested rhesus monkeys were assessed using unbiased stereology to quantify the density of activated microglia (LN3 antibody positive) and phagocytic microglia (galectin-3 (Gal-3) antibody positive) in three white matter regions: the corpus callosum, cingulum bundle (CGB), and frontal white matter (FWM). LN3 cell density was significantly increased in the CGB, whereas Gal-3 cell density was significantly increased in all regions. Increases in Gal-3 cell density in the FWM were associated with cognitive impairment. In the FWM of old animals, Gal-3-positive microglia were classified by morphological subtype as ramified, hypertrophic, or amoeboid. The densities of hypertrophic and amoeboid microglia significantly correlated with cognitive impairment. Finally, microglia were double-labeled with LN3 and Gal-3 showing that 91% of Gal-3 cells were also LN3 positive, thus expressing an "activated" phenotype. Furthermore, 15% of all double-labeled cells formed phagocytic cups. Overall, these results suggest that microglia become activated in white matter with age where the majority express a phagocytic phenotype. We hypothesize that age-related phagocytic activation of microglia is a response to accumulating myelin pathology. The association of Gal-3 in the FWM with cognitive impairment may reflect regional differences in damage or dysfunction of normal clearance mechanisms.
Corley, Janie; Gow, Alan J; Starr, John M; Deary, Ian J
We tested the hypothesis that the previously reported association between a higher body mass index (BMI) and poorer cognition in later adulthood is an artifact of confounding by previous cognitive ability and socioeconomic status. Participants were 1,079 adults aged about 70 years in the Lothian Birth Cohort 1936 Study, on whom there are IQ data from age 11. Cognitive outcome measures included: IQ at age 70 using the same test that was administered at age 11; composite measures of general cognitive ability (g factor), speed of information processing, and memory; and two tests of verbal ability. People classified as overweight or obese in later adulthood had significantly lower scores on tests of childhood IQ, age 70 IQ, g factor, and verbal ability. There was no significant association with processing speed or memory performance. After adjusting for childhood IQ and social class in general linear models, associations with age 70 IQ and g factor were nonsignificant or attenuated. However, throughout the models, there was a persistent (inverse) relationship between BMI and performance on the National Adult Reading Test (NART) and Wechsler Test of Adult Reading (WTAR), which remained significant after full adjustment for all sociodemographic and health covariates (for the NART, p = .025; for the WTAR, p = .011). The findings suggest that the previously reported BMI-cognition associations in later adulthood could be largely accounted for by prior ability and socioeconomic status, and by the possible influence of these factors on the adoption of health behaviors in adulthood.
Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D
Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines.
Aharonovich, Efrat; Nunes, Edward; Hasin, Deborah
Cognitive-behavioral therapy (CBT) depends on adequate cognitive functioning in patients, but prolonged cocaine use may impair cognitive functioning. Therefore, cognitive impairment may impede the ability of cocaine abusers to benefit from CBT. To begin to address this issue, we investigated the relationship between cognitive impairment and two treatment outcomes, therapy completion and abstention. Eighteen carefully screened non-depressed cocaine-dependent patients in a psychopharmacological clinical trial were administered the MicroCog computerized battery to assess cognitive performance at treatment entry. T-tests were used to compare cognitive functioning between completers (patients remaining in treatment at least 12 weeks) and dropouts. The results indicated that treatment completers had demonstrated significantly better cognitive performance at baseline than patients who dropped out of treatment. Cognitive domains that significantly distinguished between treatment completers and dropouts were attention, mental reasoning and spatial processing. This study provides preliminary evidence that cognitive impairments may decrease treatment retention and abstinence in CBT of cocaine dependence.
Many students with cognitive impairments are not afforded the opportunity to develop their potential as readers. A review of the literature reveals that few researchers have evaluated the effects of phonics instruction on the reading skills of students with cognitive impairments. The purpose of this study was to test the effectiveness of a…
McConnell, David; Feldman, Maurice; Aunos, Marjorie; Prasad, Narasimha
Objectives: The aim of this study was to determine the prevalence of parental cognitive impairment in cases opened for child maltreatment investigation in Canada, and to examine the relationship between parental cognitive impairment and maltreatment investigation outcomes including substantiation, case disposition and court application. Methods:…
Bora, Emre; Yücel, Murat; Pantelis, Christos
It has recently been suggested that cognitive impairment should be included in the diagnostic criteria of schizophrenia. One of the main arguments in support of this suggestion has been the hope that cognitive impairment can help distinguish schizophrenia from bipolar disorder (BD). However, recent evidence shows that cognitive deficits occur in BD and persist beyond euthymia. Further, mood disorders with psychotic features might be expected to manifest greater cognitive impairment, which further complicates the potential to differentiate these disorders. The goal of the current meta-analysis was to examine the magnitude and characteristics of cognitive impairments in affective psychoses (AP). A systematic search of the existing literature sourced 27 studies that met the inclusion criteria. These studies compared cognitive performances of 763 patients with AP (550 BD and 213 major depressive disorder) and 1823 healthy controls. Meta-regression and subgroup analyses were used to examine the effects of moderator variables. Meta-analyses of these studies showed that patients with AP were impaired in all 15 cognitive tasks with large effect sizes for most measures. There were no significant differences between the magnitude of impairments between the BD and major depressive disorder groups. The largest effect size was found for symbol coding, stroop task, verbal learning, and category fluency, reflecting impairments in elementary and complex aspects of attentional processing, as well as learning and memory. In general, the pattern of cognitive impairments in AP was similar to reported findings in euthymic patients with BD, but relatively more pronounced.
Dittrich, Kerstin; Stahl, Christoph
Load theory predicts that concurrent cognitive load impairs selective attention. For visual stimuli, it has been shown that this impairment can be selective: Distraction was specifically increased when the stimulus material used in the cognitive load task matches that of the selective attention task. Here, we report four experiments that…
Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James
White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…
Vassilaki, Maria; Aakre, Jeremiah A.; Cha, Ruth H.; Kremers, Walter K.; St. Sauver, Jennifer L.; Mielke, Michelle M.; Geda, Yonas E.; Machulda, Mary M.; Knopman, David S.; Petersen, Ronald C.; Roberts, Rosebud O
OBJECTIVES To determine the association of multiple chronic conditions with risk of incident mild cognitive impairment (MCI)/dementia. DESIGN Prospective cohort study SETTING Olmsted County, Minnesota. PARTICIPANTS Cognitively normal individuals (N=2,176) enrolled in the Mayo Clinic Study of Aging (MCSA). MEASUREMENTS Participants were randomly selected from the community and evaluated by a study coordinator, a physician, and underwent neuropsychometric testing at baseline and at 15-month intervals to assess diagnoses of MCI and dementia. We electronically captured information on International Classification of Diseases, ninth revision (ICD-9) codes for chronic conditions in the five years prior to enrollment using the Rochester Epidemiology Project medical records linkage system. We defined multimorbidity as having two or more chronic conditions and examined the association of multimorbidity with MCI/dementia using Cox proportional hazards models. RESULTS Among 2,176 cognitively normal participants (mean [±SD] age 78.5 [±5.2] years; 50.6% men), 1,884 (86.6%) had multimorbidity. The risk of MCI/dementia was elevated in persons with multimorbidity (hazard ratio [HR]: 1.38; 95% confidence interval [CI], 1.05–1.82). The HR was stronger in persons with ≥4 conditions (HR: 1.61; 95%CI, 1.21–2.13) compared to persons with only 0 or 1 conditions, and for men (HR: 1.53, 95% CI, 1.01– 2.31) than for women (HR: 1.20, 95% CI, 0.83– 1.74). CONCLUSION In older adults, having multiple chronic conditions is associated with an increased risk of MCI/dementia. This is consistent with the hypothesis that multiple etiologies may contribute to MCI and late-life dementia. Preventing chronic diseases may be beneficial in delaying or preventing MCI or dementia. PMID:26311270
Enriquez-Geppert, Stefanie; Barceló, Francisco
Age-related neurocognitive effects have been observed at different levels ranging from reduced amplitudes of even-related potentials and brain oscillations, to topography changes of brain activity. However, their association remains incompletely understood. We investigated time-frequency and time-course effects in functional networks underlying the P300 and their involvement in reactive control. Electroencephalographic (EEG) data of three different age groups (30 young: 18-26 years, 30 mid-aged: 49-58 years, 30 elderly: 65-75 years) was measured while they performed a cued colour/thickness switching task. Neural data was analysed concerning the targets. To consider restart, mixing, and switching processes, the targets´ position after a cue (first or third target) as well as their context in the single-task (distractor cue) or the mixed-task block (switch- or repeat cue) was analysed. P300 EEG data was decomposed by means of group-independent component and time-frequency analyses focusing on theta and beta oscillations. RTs generally slowed down with age (main effect group), and effects were specifically strong in targets after a switching cue (larger Cohens d). Peaking at around 300 ms, we detected five functionally independent networks reflecting the multicomponent process underlying task-switching. These networks differed in terms of their topography (parietal and frontal), their involvement in task processes (switch-specific, mixing-, restart-, and single-task processes) and in terms of frequency effects. All were affected by age, as indicated by amplitude changes of the target-P300 and power reductions most consistently shown in beta oscillations. Most extensive age-related changes were observed in one parietal network sensitive to mixing and restart processes. Changes included a topography shift, P300 and beta amplitudes, and were ongoing in the elderly group.
Förstl, H; Bickel, H; Lautenschlager, N; Riemenschneider, M; Kurz, A
Forgetfulness is defined as a subjectively bothersome impairment of the ability to recall facts that are unequivocally known to be stored in the memory. Objectifiable memory deficits may accompany numerous physical and neurological illnesses, but may also be seen in depressive states. Below average-for-age cognitive performances that do not reach the level of dementia are referred to as mild cognitive impairment, which in some cases represents a pre-dementia stage of Alzheimer's disease. Its recognition and differentiation from age-related performance deficits is now possible using simple, but sensitive neuropsychological tests. An important aim of the diagnostic work-up is the recognition of potentially reversible causes. For this purpose, physical examination and laboratory investigations are helpful. Structural and functional imaging procedures can provide information about cerebral causes. Biochemical indicators of neurogenerative processes are currently being developed. Cognitive training measures possibly have only a small and temporary effect. In patients with mild cognitive impairment, nootropic agents apparently have a symptomatic effect. Whether antidementia agents are capable of stopping the progress of mild cognitive impairment to full-blown dementia is currently being investigated in ongoing trials.
Peltz, Carrie Brumback; Gratton, Gabriele; Fabiani, Monica
Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP) work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span (OSPAN) task (a measure of attention control) is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively). To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction time task. For both age groups (a) participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b) participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life. PMID:21887150
Allen, Nara L.
The aim of the present study was to investigate the effects of a computer cognitive training program on depression levels in older mildly cognitive impaired individuals. Peterson et al. (1999), defines mild cognitive impairment (MCI) as a transitional stage in which an individual's memory deteriorates and his likelihood of developing Alzheimer's…
Falah, Masoumeh; Najafi, Mohammad; Houshmand, Massoud; Farhadi, Mohammad
Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apoptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. PMID:27555755
Meyer-Ruesenberg, B; Richard, G
Different forms of age-related macular degeneration (AMD) can lead to massive visual impairment up to blindness. Therefore, AMD has a high impact on patients' daily life and causes restrictions of their psychological well-being, autonomy and mobility. These restrictions influence their quality of life. It is difficult to define the term "quality of life". It consists of different aspects that can be measured with psychometric tests. Besides the general health status and the psychological well-being, the vision-specific functional status plays a central role for determining the quality of life of AMD patients. To compare the impact of different diseases on the quality of life, the utility analysis has been developed. It demonstrates the relevance of AMD for patients and shows that its impact on patients' life is comparable to those of other systemic diseases like carcinoma or HIV. The impairment of patients' quality of life by AMD is often underestimated by their attending ophthalmologists. Different medical treatments have influenced the quality of life of AMD patients. However, there is still a large group that cannot be treated. These patients benefit from rehabilitation with low vision aids or psychosocial interventions. Further clinical trials at a high evidence level using valid and comparable psychometric tests are necessary to improve the therapy for and the rehabilitation of AMD patients and to increase their quality of life.
Baehr, Leslie M.; West, Daniel W.D.; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.
Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID:26826670
Carman, A J; Dacks, P A; Lane, R F; Shineman, D W; Fillit, H M
Although nothing has been proven conclusively to protect against cognitive aging, Alzheimer's disease or related dementias, decades of research suggest that specific approaches including the consumption of coffee may be effective. While coffee and caffeine are known to enhance short-term memory and cognition, some limited research also suggests that long-term use may protect against cognitive decline or dementia. In vitro and pre-clinical animal models have identified plausible neuroprotective mechanisms of action of both caffeine and other bioactive components of coffee, though epidemiology has produced mixed results. Some studies suggest a protective association while others report no benefit. To our knowledge, no evidence has been gathered from randomized controlled trials. Although moderate consumption of caffeinated coffee is generally safe for healthy people, it may not be for everyone, since comorbidities and personal genetics influence potential benefits and risks. Future studies could include short-term clinical trials with biomarker outcomes to validate findings from pre-clinical models and improved epidemiological studies that incorporate more standardized methods of data collection and analysis. Given the enormous economic and emotional toll threatened by the current epidemic of Alzheimer's disease and other dementias, it is critically important to validate potential prevention strategies such as coffee and caffeine.
Muris, Peter; Mayer, Birgit; Freher, Nancy Kramer; Duncan, Sylvana; van den Hout, Annemiek
The present study examined age-related patterns in children's anxiety-related interpretations and internal attributions of physical symptoms. A large sample of 388 children aged between 4 and 13 years completed a vignette paradigm during which they had to explain the emotional response of the main character who experienced anxiety-related physical symptoms in a variety of daily situations. In addition, children completed measures of cognitive development and anxiety sensitivity. Results demonstrated that age, cognitive development, and anxiety sensitivity were all positively related to children's ability to perceive physical symptoms as a signal of anxiety and making internal attributions. Further, while a substantial proportion of the younger children (i.e., <7 years) were able to make a valid anxiety-related interpretation of a physical symptom, very few were capable of making an internal attribution, which means that children of this age lack the developmental prerequisites for applying physical symptoms-based theories of childhood anxiety.
Hayes, Tamara L.; Riley, Thomas; Mattek, Nora; Pavel, Misha; Kaye, Jeffrey A.
We explored the relationship between sleep disturbances and mild cognitive impairment (MCI) in community-dwelling seniors. Recent evidence suggests that sleep habits are differentially compromised in different subtypes of MCI, but the relationship between sleep disruption and MCI remains poorly understood. We gathered daily objective measures of sleep disturbance from 45 seniors, including 16 with MCI (mean age 86.9 ± 4.3 years), over a six month period. We also collected self-report measures of sleep disturbance. Although there were no differences between groups in any of our self-report measures, we found that amnestic MCI (aMCI) volunteers had less disturbed sleep than both non-amnestic MCI (naMCI) and cognitively intact volunteers, as measured objectively by movement in bed at night (F2,1078=4.30, p=0.05), wake after sleep onset (F2,1078=41.6, p<0.001), and times up at night (F2,1078=26.7, p<0.001). The groups did not differ in total sleep time. In addition, the aMCI group had less day-to-day variability in these measures than the intact and naMCI volunteers. In general, the naMCI volunteers showed a level of disturbed sleep that was intermediate to that of aMCI and intact volunteers. These differences in sleep disruption between aMCI and naMCI may be related to differences in the pathology underlying these MCI subtypes. PMID:24145694
Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H
Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Meanage = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Díaz-Mardomingo, Carmen; García-Herranz, Sara; Pereda-Pérez, Inmaculada; Peraita, Herminia; Venero, César; Madrid, Juan Antonio; Rol, Maria Angeles
Introduction. Patients with dementia, especially Alzheimer's disease, present several circadian impairments related to an accelerated perturbation of their biological clock that is caused by the illness itself and not merely age-related. Thus, the objective of this work was to elucidate whether these circadian system alterations were already present in patients with mild cognitive impairment (MCI), as compared to healthy age-matched subjects. Methods. 40 subjects (21 patients diagnosed with MCI, 74.1 ± 1.5 y.o., and 19 healthy subjects, 71.7 ± 1.4 y.o.) were subjected to ambulatory monitoring, recording wrist skin temperature, motor activity, body position, and the integrated variable TAP (including temperature, activity, and position) for one week. Nonparametrical analyses were then applied. Results. MCI patients exhibited a significant phase advance with respect to the healthy group for the following phase markers: temperature M5 (mean ± SEM: 04:20 ± 00:21 versus 02:52 ± 00:21) and L10 (14:35 ± 00:27 versus 13:24 ± 00:16) and TAP L5 (04:18 ± 00:14 versus 02:55 ± 00:30) and M10 (14:30 ± 00:18 versus 13:28 ± 00:23). Conclusions. These results suggest that significant advances in the biological clock begin to occur in MCI patients, evidenced by an accelerated aging of the circadian clock, as compared to a healthy population of the same age. PMID:25157363
Zhao, Jingjing; Yao, Li; Wang, Changqing; Sun, Yun; Sun, Zhongwu
Patients who survive critical illness commonly suffer cognitive impairments. We aimed to study the effects of cognitive intervention to treat the long-term impairments observed among different populations of intensive care unit (ICU) survivors. The results showed that the intervention significantly suppressed the deterioration of cognitive function in these patients. Medical and neurological ICU survivors were more susceptible than post-anaesthesia ICU patients to severe cognitive damage. In the former, the deterioration of impairments can be slowed by cognitive intervention. In comparison, intervention exerted significantly positive effects on the recovery of the cognitive functions of post-anaesthesia care unit patients. Furthermore, young populations were more likely than older populations to recover from acute cognitive impairments, and the impairment observed among the older population seemed to be multi-factorial and irreversible.
Post-stroke cognitive impairment occurs frequently in the patients with stroke. The prevalence of post-stroke cognitive impairment ranges from 20% to 80%, which varies for the difference between the countries, the races, and the diagnostic criteria. The risk of post-stroke cognitive impairment is related to both the demographic factors like age, education and occupation and vascular factors. The underlying mechanisms of post-stroke cognitive impairment are not known in detail. However, the neuroanatomical lesions caused by the stroke on strategic areas such as the hippocampus and the white matter lesions (WMLs), the cerebral microbleeds (CMBs) due to the small cerebrovascular diseases and the mixed AD with stroke, alone or in combination, contribute to the pathogenesis of post-stroke cognitive impairment. The treatment of post-stroke cognitive impairment may benefit not only from the anti-dementia drugs, but also the manage measures on cerebrovascular diseases. In this review, we will describe the epidemiological features and the mechanisms of post-stroke cognitive impairment, and discuss the promising management strategies for these patients. PMID:25333055
Herrera, C.; Chambon, C.; Michel, B. F.; Paban, V.; Alescio-Lautier, B.
Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a…
Zakharov, V V; Gromova, D O
Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. The prevalence of MCI among elderly people is 12-17% but the risk of progression of cognitive impairment and development of dementia during 5 years is up to 70%. Cerebral vascular diseases and initial stages of neurodegenerative processes are the cause of MCI. Clinical characteristics of MCI depend on the main etiological factor. To decrease the severity of symptoms and prevent the progression of cognitive impairment in MCI patients, pharmacotherapy and non-medication methods, including diet optimization, stimulation of mental and physical activity, are used. Dopaminergic and noradrenergic therapy is most prevalent among pharmacological methods.
Yang, Y Tony; Kels, Charles G
Cognitive impairment afflicts an estimated 16 million people in the United States. Wandering is a concerning behavior associated with cognitive impairment, as it may threaten patient safety. The risks posed by wandering place severe burdens on both professional and informal caregivers, as well as law enforcement institutions throughout the United States. As such, location trackers that could reduce this burden have become increasingly prevalent. As with many assistive technologies, the substantial promise of location trackers is counterbalanced by potential pitfalls with respect to loss of privacy and autonomy. This article reviews the ethical issues raised by electronic monitoring of cognitively impaired persons, with the goal of transcending a narrow focus on decisional capacity in favor of a patient-centered framework that is applicable and adjustable at different stages of cognitive decline. Balancing the ethical principles of beneficence and respect in treating cognitively impaired persons goes beyond the necessary step of evaluating decision-making capacity to include partnering with families, caretakers, and cognitively impaired individuals who wander in a collaborative coalition of care. An approach emphasizing the individual needs of patients and caretakers is best suited to finding solutions that implement tracking technologies in ways that both protect and empower the cognitively impaired.
Huyghe, Jeroen R.; Van Laer, Lut; Hendrickx, Jan-Jaap; Fransen, Erik; Demeester, Kelly; Topsakal, Vedat; Kunst, Sylvia; Manninen, Minna; Jensen, Mona; Bonaconsa, Amanda; Mazzoli, Manuela; Baur, Manuela; Hannula, Samuli; Mäki-Torkko, Elina; Espeso, Angeles; Van Eyken, Els; Flaquer, Antonia; Becker, Christian; Stephens, Dafydd; Sorri, Martti; Orzan, Eva; Bille, Michael; Parving, Agnete; Pyykkö, Ilmari; Cremers, Cor W.R.J.; Kremer, Hannie; Van de Heyning, Paul H.; Wienker, Thomas F.; Nürnberg, Peter; Pfister, Markus; Van Camp, Guy
Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait. PMID:18760390
Huyghe, Jeroen R; Van Laer, Lut; Hendrickx, Jan-Jaap; Fransen, Erik; Demeester, Kelly; Topsakal, Vedat; Kunst, Sylvia; Manninen, Minna; Jensen, Mona; Bonaconsa, Amanda; Mazzoli, Manuela; Baur, Manuela; Hannula, Samuli; Mäki-Torkko, Elina; Espeso, Angeles; Van Eyken, Els; Flaquer, Antonia; Becker, Christian; Stephens, Dafydd; Sorri, Martti; Orzan, Eva; Bille, Michael; Parving, Agnete; Pyykkö, Ilmari; Cremers, Cor W R J; Kremer, Hannie; Van de Heyning, Paul H; Wienker, Thomas F; Nürnberg, Peter; Pfister, Markus; Van Camp, Guy
Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.
Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun
Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.
Deak, Ferenc; Freeman, Willard M.; Ungvari, Zoltan; Csiszar, Anna
As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer’s disease. PMID:26590911
Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E
As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.
Joseph, J A; Shukitt-Hale, B; Denisova, N A; Prior, R L; Cao, G; Martin, A; Taglialatela, G; Bickford, P C
Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.
Goldman, Jennifer G; Weis, Holly; Stebbins, Glenn; Bernard, Bryan; Goetz, Christopher G
Mild cognitive impairment is increasingly recognized as a construct in Parkinson's disease (PD) and occurs in about 25% of nondemented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD-MCI) is broad. PD-MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single- and multiple-domain impairment. However, it is unclear whether patients with different PD-MCI subtypes also differ in other clinical characteristics in addition to cognitive profile. We studied 128 PD-MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD-MCI subtypes. We found varying proportions of impairment subtypes: nonamnestic single domain, 47.7%; amnestic multiple domain, 24.2%; amnestic single domain, 18.8%; and nonamnestic multiple domain, 9.5%. Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD-MCI subtypes differed in their motor features, with nonamnestic multiple-domain PD-MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD-MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, and vascular disease were not significant. Thus, in addition to differing cognitive profiles, PD-MCI subtypes differed in motor phenotype and severity but not in mood, behavioral, or vascular comorbidities. Greater postural instability and gait disturbances in the nonamnestic multiple-domain subtype emphasize shared nondopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD-MCI.
Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.
Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0
Leigh, Andrew James; O'Hanlon, Katie; Sheldrick, Russell; Surr, Claire; Hare, Dougal Julian
Person-centred care can improve the well-being of patients and is therefore a key driver in healthcare developments in the UK. The current study aims to investigate the complex relationship between cognitive impairment, dependency and well-being in people with a wide range of acquired brain and spinal injuries. Sixty-five participants, with varied acquired brain and spinal injuries, were selected by convenience sampling from six inpatient clinical neuroscience settings. Participants were observed using Dementia Care Mapping - Neurorehabilitation (DCM-NR) and categorised based on severity of cognitive impairment. A significant difference in the behaviours participants engaged in, their well-being and dependency was found between the severe cognitive impairment group and the mild, moderate or no cognitive impairment groups. Dependency and cognitive impairment accounted for 23.9% of the variance in well-ill-being scores and 17.2% of the variance in potential for positive engagement. The current study highlights the impact of severe cognitive impairment and dependency on the behaviours patients engaged in and their well-being. It also affirms the utility of DCM-NR in providing insights into patient experience. Consideration is given to developing DCM-NR as a process that may improve person-centred care in neuroscience settings.
Delgado-Alvarado, Manuel; Gago, Belén; Navalpotro-Gomez, Irene; Jiménez-Urbieta, Haritz; Rodriguez-Oroz, María C
Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society.
Brites, Dora; Fernandes, Adelaide
Bilirubin-induced neurologic dysfunction (BIND) and classical kernicterus are clinical manifestations of moderate to severe hyperbilirubinemia whenever bilirubin levels exceed the capacity of the brain defensive mechanisms in preventing its entrance and cytotoxicity. In such circumstances and depending on the associated co-morbidities, bilirubin accumulation may lead to short- or long-term neurodevelopmental disabilities, which may include deficits in auditory, cognitive, and motor processing. Neuronal cell death, astrocytic reactivity, and microglia activation are part of the bilirubin-induced pathogenesis. Less understood is how abnormal growth and maturation of oligodendrocytes may impact on brain development, affecting the formation of myelin tracts. Based on in-vitro and in-vivo models, as well as in clinical cases presented here, we propose the existence of impaired myelination by bilirubin with long-term sequelae, mainly in pre-term infants. Sensitive time-windows are highlighted and centered on the different developmental-dependent impairments determined by bilirubin, and the influence of sepsis and hypoxia is reviewed.
King, Margaret K.; Pardo, Marta; Cheng, Yuyan; Downey, Kimberlee; Jope, Richard S.; Beurel, Eléonore
Impairment of cognitive processes is a devastating outcome of many diseases, injuries, and drugs affecting the central nervous system (CNS). Most often, very little can be done by available therapeutic interventions to improve cognitive functions. Here we review evidence that inhibition of glycogen synthase kinase-3 (GSK3) ameliorates cognitive deficits in a wide variety of animal models of CNS diseases, including Alzheimer's disease, Fragile X syndrome, Down syndrome, Parkinson's disease, spinocerebellar ataxia type 1, traumatic brain injury, and others. GSK3 inhibitors also improve cognition following impairments caused by therapeutic interventions, such as cranial irradiation for brain tumors. These findings demonstrate that GSK3 inhibitors are able to ameliorate cognitive impairments caused by a diverse array of diseases, injury, and treatments. The improvements in impaired cognition instilled by administration of GSK3 inhibitors appear to involve a variety of different mechanisms, such as supporting long-term potentiation and diminishing long-term depression, promotion of neurogenesis, reduction of inflammation, and increasing a number of neuroprotective mechanisms. The potential for GSK3 inhibitors to repair cognitive deficits associated with many conditions warrants further investigation of their potential for therapeutic interventions, particularly considering the current dearth of treatments available to reduce loss of cognitive functions. PMID:23916593
Coon, David W.; Thompson, Larry W.; Gallagher-Thompson, Dolores
There is growing evidence that psychosocial treatments incorporating behavioral intervention strategies can be effective in the treatment of depression in older adults with cognitive impairment. However, less work with such cases has focused on the use of cognitive interventions in tandem with these behavioral intervention strategies. This case…
López-Álvarez, Jorge; Zea Sevilla, María Ascensión; Agüera Ortiz, Luis; Fernández Blázquez, Miguel Ángel; Valentí Soler, Meritxell; Martínez-Martín, Pablo
The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed.
Shields, Grant S; Trainor, Brian C; Lam, Jovian C W; Yonelinas, Andrew P
Psychosocial stress influences cognitive abilities, such as long-term memory retrieval. However, less is known about the effects of stress on cognitive flexibility, which is mediated by different neurobiological circuits and could thus be regulated by different neuroendocrine pathways. In this study, we randomly assigned healthy adults to an acute stress induction or control condition and subsequently assessed participants' cognitive flexibility using an open-source version of the Wisconsin Card Sort task. Drawing on work in rodents, we hypothesized that stress would have stronger impairing effects on cognitive flexibility in men than women. As predicted, we found that stress impaired cognitive flexibility in men but did not significantly affect women. Our results thus indicate that stress exerts sex-specific effects on cognitive flexibility in humans and add to the growing body of research highlighting the need to consider sex differences in effects of stress.
Jin, Xiaojie; Pang, Xiuhong; Li, Jiping; Chai, Yongchuan; Li, Lei; Zhang, Yi; Zhang, Luping; Zhang, Zhihua; Wu, Wenjing; Zhang, Qin; Hu, Xianting; Sun, Jingwen; Jiang, Xuemei; Fan, Zhuping; Huang, Zhiwu; Wu, Hao
Several single nucleotide polymorphisms (SNPs) of the Glutamate metabotrophic receptor 7 gene (GRM7) have recently been identified by the genome-wide association study (GWAS) as potentially playing a role in susceptibility to age-related hearing impairment (ARHI), however this has not been validated in the Han Chinese population. The aim of this study was to determine if these SNPs are also associated with ARHI in an elderly male Han Chinese population. In this case-control candidate genes association study, a total of 982 men with ARHI and 324 normal-hearing controls subjects were studied. Using K-means cluster analysis, four audiogram shape subtypes of ARHI were identified in the case group: ‘‘flat shape (FL)’’, ‘‘sloping shape (SL)’’, ‘‘2-4 kHz abrupt loss (AL) shape’’ and ‘‘8 kHz dip (8D) shape’’. Results suggested that the SNP rs11928865 (A>T) of GRM7 was significantly associated with ARHI after adjusting for non-genetic factors (p= 0.000472, OR= 1.599, 95%CI= 1.229~2.081). Furthermore, frequency of TT genotype (rs11928865) were significant higher in the SL subgroup and AL subgroup with compared to controls group (p= 9.41E-05, OR= 1.945, 95%CI= 1.393~2.715; p= 0.000109, OR= 1.915, 95%CI= 1.378~2.661 adjusted, respectively) after Bonferroni correction. However, there wasn’t significant difference in the frequency of the TT genotype between cases in the FL subgroup or the 8D subgroup with when compared with controls. Results of the current study suggest that, in an elderly male Han Chinese population, GRM7 SNP rs11928865 (TT) occurs more frequently in ARHI patients with SL and AL phenotype patterns. PMID:24146964
Clark, Simon J; Perveen, Rahat; Hakobyan, Svetlana; Morgan, B Paul; Sim, Robert B; Bishop, Paul N; Day, Anthony J
Age-related macular degeneration (AMD) is the predominant cause of blindness in the industrialized world where destruction of the macula, i.e. the central region of the retina, results in loss of vision. AMD is preceded by the formation of deposits in the macula, which accumulate between the Bruch's membrane and the retinal pigment epithelium (RPE). These deposits are associated with complement-mediated inflammation and perturb retinal function. Recent genetic association studies have demonstrated that a common allele (402H) of the complement factor H (CFH) gene is a major risk factor for the development of AMD; CFH suppresses complement activation on host tissues where it is believed to bind via its interaction with polyanionic structures. We have shown previously that this coding change (Y402H; from a tyrosine to histidine residue) alters the binding of the CFH protein to sulfated polysaccharides. Here we demonstrate that the AMD-associated polymorphism profoundly affects CFH binding to sites within human macula. Notably, the AMD-associated 402H variant binds less well to heparan sulfate and dermatan sulfate glycosaminoglycans within Bruch's membrane when compared with the 402Y form; both allotypes exhibit a similar level of binding to the RPE. We propose that the impaired binding of the 402H variant to Bruch's membrane results in an overactivation of the complement pathway leading to local chronic inflammation and thus contributes directly to the development and/or progression of AMD. These studies therefore provide a putative disease mechanism and add weight to the genetic association studies that implicate the 402H allele as an important risk factor in AMD.
Laspiur, Juliana Pérez; Anderson, Eric R.; Ciborowski, Pawel; Wojna, Valerie; Rozek, Wojciech; Duan, Fenghai; Mayo, Raul; Rodríguez, Elaine; Plaud-Valentín, Marinés; Rodríguez-Orengo, José; Gendelman, Howard E.; Meléndez, Loyda M.
Cognitive impairment remains a major complication of advanced human immunodeficiency virus (HIV) infection despite the wide spread use of anti-retroviral therapy. Diagnosis is made by exclusion making biomarkers of great potential use. Thus, we used an integrated proteomics platform to assess cerebrospinal fluid protein profiles from 50 HIV-1 seropositive Hispanic women. Nine of 38 proteins identified were unique in those patients with cognitive impairment. These proteins were linked to cell signaling, structural function, and antioxidant activities. This work highlights, in a preliminary manner, the utility of proteomic profiling for biomarker discovery for HIV-1 associated cognitive dysfunction. PMID:17950469
Mossello, Enrico; Simoni, David
High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment.
Fleming, Valarie B.
Individuals with mild cognitive impairment (MCI) may present with subtle declines in linguistic ability that go undetected by tasks not challenging enough to tax a relatively intact cognitive-linguistic system. This study was designed to replicate and extend a previous study of cognitive-linguistic ability in MCI using a complex discourse…
Hunsaker, Amanda E; Terhorst, Lauren; Gentry, Amanda; Lingler, Jennifer H
The current exploratory investigation aims to establish the reliability and validity of a hope measure, the Herth Hope Index, among families impacted by early cognitive impairment (N = 96). Exploratory factor analysis was used to examine the dimensionality of the measure. Bivariate analyses were used to examine construct validity. The sample had moderately high hope scores. A two-factor structure emerged from the factor analysis, explaining 51.44% of the variance. Both factors exhibited strong internal consistency (Cronbach's alphas ranged from .83 to .86). Satisfaction with social support was positively associated with hope, supporting convergent validity. Neurocognitive status, illness insight, and depression were not associated with hope, indicating discriminant validity. Families impacted by cognitive impairment may maintain hope in the face of a potentially progressive illness, regardless of cognitive status. The Herth Hope Index can be utilized as a reliable and valid measure of hope by practitioners providing support to families impacted by cognitive impairment.
Yaffe, Kristine; Ackerson, Lynn; Hoang, Tina D.; Go, Alan S.; Maguire, Maureen G.; Ying, Gui-Shuang; Daniel, Ebenezer; Bazzano, Lydia A.; Coleman, Martha; Cohen, Debbie L.; Kusek, John W.; Ojo, Akinlolu; Seliger, Stephen; Xie, Dawei; Grunwald, Juan E.
Background Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small vessel disease. This relationship has not been evaluated among persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. Study Design Cross-sectional study Setting & Participants 588 participants ≥ 52 years old with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study Predictor Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. Outcomes Neuropsychological battery of six cognitive tests Measurements Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy adjusting for age, race, sex, education, and medical comorbidities. Results The mean age of the cohort was 65.3 +/− 5.6 (SD) years; 51.9% were non-White, and 52.6% were male. The prevalence of retinopathy was 30.1% and 14.3% for cognitive impairment. Compared to those without retinopathy, participants with retinopathy had increased likelihood of cognitive impairment on executive function (35.1% vs. 11.5%; OR, 3.4; 95% CI, 2.0-6.0), attention (26.7% vs. 7.3%; OR, 3.0; 95% CI, 1.8-4.9), and naming (26.0% vs. 10.0%; OR, 2.1; 95% CI, 1.2-3.4) after multivariable adjustment. Increased level of retinopathy was also associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. Limitations Unknown temporal relationship between retinopathy and impairment. Conclusions In adults with CKD, retinopathy is
Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.
Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…
Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J.; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard
Abstract Background: The temporal relationship of cognitive deficit and functional impairment in Alzheimer’s disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. Objective: To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Methods: Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. Results: In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Conclusions: Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process. PMID:26402769
Souza, Leandro Cattelan; Antunes, Michelle Silva; Filho, Carlos Borges; Del Fabbro, Lucian; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Donato, Franciele; Prigol, Marina; Boeira, Silvana Peterini; Jesse, Cristiano R
In this study, the effect of Chrysin (5,7-dihydroxyflavone), an important member of the flavonoid family, on memory impairment, oxidative stress and BDNF reduction generated by aging in mice were investigated. Young and aged mice were treated daily per 60days with Chrysin (1 and 10mg/kg; per oral, p.o.) or veichle (10ml/kg; p.o.). Mice were trained and tested in Morris Water Maze task. After the behavioural test, the levels of reactive species (RS), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the activity of Na(+), K(+)-ATPase and the levels of brain-derived neurotrophic factor (BDNF) were determined in the prefrontal cortex (PFC) and hippocampus (HC) of mice. Results demonstrated that the age-related memory decline was partially protected by Chrysin at a dose of 1mg/kg, and normalized at the dose of 10mg/kg (p<0.001). Treatment with Chrysin significantly attenuated the increase of RS levels and the inhibition of SOD, CAT and GPx activities of aged mice. Inhibition of Na(+), K(+)-ATPase activity in PFC and HP of aged mice was also attenuated by Chrysin treatment. Moreover, Chrysin marked mitigated the decrease of BDNF levels in the PFC and HC of aged mice. These results demonstrated that flavonoid Chrysin, an antioxidant compound, was able to prevent age-associated memory probably by their free radical scavenger action and modulation of BDNF production. Thus, this study indicates that Chrysin may represent a new pharmacological approach to alleviate the age-related declines during normal age, acting as an anti-aging agent.
Hamatani, Sayo; Tomotake, Masahito; Takeda, Tomoya; Kameoka, Naomi; Kawabata, Masashi; Kubo, Hiroko; Tada, Yukio; Tomioka, Yukiko; Watanabe, Shinya; Ohmori, Tetsuro
Background The purpose of this study was to investigate the characteristics of social cognition in patients with anorexia nervosa (AN). Methods Eighteen female patients with AN (mean age =35.4±8.6 years) and 18 female healthy controls (HC) (mean age =32.8±9.4 years) participated in the study. Their social cognition was assessed with the Social Cognition Screening Questionnaire (SCSQ). Results The results showed that total score of the SCSQ and scores of theory of mind and metacognition were significantly lower in AN group than those in HC group. Moreover, significant differences in theory of mind, metacognition, and total score of the SCSQ remained when the effects of depression, anxiety, and starvation were eliminated statistically. Conclusion These results suggest that patients with AN may have difficulty inferring other people’s intention and also monitoring and evaluating their own cognitive activities. Therefore, these features may explain some aspects of the pathology of AN. PMID:27785029
Eagles, J M; Beattie, J A; Restall, D B; Rawlinson, F; Hagen, S; Ashcroft, G W
STUDY OBJECTIVE--To study the association between cognitive impairment and early death in elderly patients living in the community. DESIGN--Case-control study of 410 patients assessed by the mental status questionnaire and followed up after three years. SETTING--A general practice in Inverurie, Aberdeenshire, with 14,000 patients. PATIENTS--205 Patients aged greater than or equal to 65 with cognitive impairment according to the mental status questionnaire (score less than or equal to 8) and 205 patients scoring greater than 8 on the questionnaire matched for age and sex. MAIN OUTCOME MEASURE--Death. RESULTS--The relative risk of death in the cognitively impaired patients overall was 3.5. Those patients who scored less than or equal to 7 on the mental status questionnaire were five times more likely to die than their controls. There was no difference in risk of death between those with severe or moderate cognitive impairment. CONCLUSIONS--Cognitive impairment is associated with early death. PMID:2106935
Allain, Hervé; Akwa, Yvette; Lacomblez, Lucette; Lieury, Alain; Bentué-Ferrer, Danièle
Cognitive psychology has provided clinicians with specific tools for analyzing the processes of cognition (memory, language) and executive functions (attention-concentration, abstract reasoning, planning). Neuropsychology, coupled with the neurosciences (including neuroimaging techniques), has authenticated the existence of early disorders affecting the “superior or intellectual” functions of the human brain. The prevalence of cognitive and attention disorders is high in adults because all the diseases implicating the central nervous system are associated with cognitive correlates of variable intensity depending on the disease process and the age of the patient. In some pathologies, cognitive impairment can be a leading symptom such as in schizophrenia, posttraumatic stress disorder or an emblematic stigmata as in dementia including Alzheimer’s disease. Paradoxically, public health authorities have only recognized as medications for improving cognitive symptoms those with proven efficacy in the symptomatic treatment of patients with Alzheimer’s disease; the other cognitive impairments are relegated to the orphanage of syndromes and symptoms dispossessed of medication. The purpose of this review is to promote a true “pharmacology of cognition” based on the recent knowledge in neurosciences. Data from adult human beings, mainly concerning memory, language, and attention processes, will be reported. “Drug therapeutic strategies” for improving cognition (except for memory function) are currently rather scarce, but promising perspectives for a new neurobiological approach to cognitive pharmacology will be highlighted. PMID:19300541
Widera, Eric; Steenpass, Veronika; Marson, Daniel; Sudore, Rebecca
Financial capacity is the ability to manage money and financial assets in ways that meet a person’s needs and which are consistent with his/her values and self-interest. Financial capacity is essential for an individual to function independently in our society; however, dementia eventually leads to a complete loss of financial capacity. Many patients with cognitive impairment and their families turn to their primary care clinician for help with financial impairment, yet most clinicians do not understand their role or how to help. We review the prevalence and impact of financial incapacity in older adults with cognitive impairment. We also articulate the role of the primary clinician which includes: (1) educating older adult patients and families about the need for advance financial planning; (2) recognizing signs of possible impaired financial capacity; (3) assessing financial impairments in cognitively impaired adults; (4) recommending interventions to help patients maintain financial independence; and (5) knowing when and to whom to make medical and legal referrals. Clearly delineating the clinician’s role in financial impairment can lead to the establishment of effective financial protections and can limit the economic, psychological, and legal hardships of financial incapacity on patients with dementia and their families. PMID:21325186
Iverson, Grant L.; Brooks, Brian L.; Langenecker, Scott A.; Young, Allan H.
Background We hypothesized that only a minority of patients with mood disorders have measurable cognitive impairment, and this minority drives the small-to-medium effect sizes detected in group studies. Removal of this minority from group statistical analyses will illustrate that the majority appear to have broadly normal cognitive functioning. Methods Participants were adults between the ages of 20 and 54, including 659 healthy control subjects, 84 unmedicated outpatients diagnosed with depression, 59 outpatients diagnosed with depression who were on medications at the time of the evaluation, and 43 outpatients with bipolar disorder. All completed the CNS Vital Signs computerized cognitive screening battery. Results The prevalence rates of low cognitive test scores were calculated for the healthy control subjects and the patients with mood disorders. Having two scores at or below the 5th percentile occurred in 31.2% of the patients and only 8.2% of the control subjects [χ2(1)=66.67, p<.0001; Odds Ratio=5.1, 95% CI=3.4–7.7]. For the control subjects, this low false positive rate for cognitive impairment was maintained across age groups, sexes, and education levels. A larger proportion of patients with bipolar disorder (41.9%) than patients with depression (27.1–28.6%) met this criterion for cognitive impairment. Conclusions This study suggests that cognitive impairment associated with mood disorders is limited to a minority of patients with the majority being broadly cognitively normal. Future research should determine if this identified subgroup has neuroanatomical, neurophysiological, or neuroendocrine abnormalities. Cognitive screening tools of this type might be useful in selecting participants for studies. PMID:21439647
Ownby, Raymond L; Acevedo, Amarilis
Background In spite of treatment advances, HIV infection is associated with cognitive deficits. This is even more important as many persons with HIV infection age and experience age-related cognitive impairments. Both computer-based cognitive training and transcranial direct current stimulation (tDCS) have shown promise as interventions to improve cognitive function. In this study, we investigate the acceptability and efficacy of cognitive training with and without tDCS in older persons with HIV. Patients and methods In this single-blind randomized study, participants were 14 individuals of whom 11 completed study procedures (mean age =51.5 years; nine men and two women) with HIV-related mild neurocognitive disorder. Participants completed a battery of neuropsychological and self-report measures and then six 20-minute cognitive training sessions while receiving either active or sham anodal tDCS over the left dorsolateral prefrontal cortex. After training, participants completed the same measures. Success of the blind and participant reactions were assessed during a final interview. Assessments were completed by an assessor blind to treatment assignment. Pre- and post-training changes were evaluated via analysis of covariance yielding estimates of effect size. Results All participants believed that they had been assigned to active treatment; nine of the 11 believed that the intervention had improved their cognitive functioning. Both participants who felt the intervention was ineffective were assigned to the sham condition. None of the planned tested interactions of time with treatment was significant, but 12 of 13 favored tDCS (P=0.08). All participants indicated that they would participate in similar studies in the future. Conclusion Results show that both cognitive training via computer game playing and tDCS were well accepted by older persons with HIV infection. Results are suggestive that tDCS may improve cognitive function in persons with HIV infection. Further
Ficker, Lisa J.; Lysack, Cathy L.; Hanna, Mena; Lichtenberg, Peter A.
Objectives The Center for Disease Control began to assess Perceived Cognitive Impairment in 2009, yet there has been no in-depth study of how perceived decline in thinking or memory skills may be associated to the health and lifestyle of an independent community-dwelling older person. Among urban-dwelling older African Americans who are at elevated risk for cognitive impairment and dementia, we know even less regarding the interaction of these risk factors. Method Five hundred and one African American elders (n = 501) between the ages of 55 and 95 with an average age of 70.73 years (SD = 8.6 years) participated in telephone interviews. Results Approximately one-third of the elders reported that their memory, thinking skills, or ability to reason was worse than a year ago (n = 150; 29.9%) and 25% of this group (n = 38) reported that this Perceived Cognitive Impairment impacted their daily activities and/or warranted a consultation with their doctor. Bivariate analyses indicated that Perceived Cognitive Impairment was associated with increased health problems, mobility limitations, depressed mood, and lower social functioning. Conclusion Elders who reported that cognitive problems impacted their daily functioning reported the greatest health and mental health problems. Perceived Cognitive Impairment is an important health variable with implications for an older adult’s overall health, mobility, and mental health. PMID:24328435
Loh, Kah Poh; Janelsins, Michelle C.; Mohile, Supriya G.; Holmes, Holly M.; Hsu, Tina; Inouye, Sharon K.; Karuturi, Meghan S.; Kimmick, Gretchen G.; Lichtman, Stuart M.; Magnuson, Allison; Whitehead, Mary I.; Wong, Melisa L.; Ahles, Tim A.
Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer. PMID:27197918
Kalantarian, Shadi; Stern, Theodore A.; Mansour, Moussa; Ruskin, Jeremy N.
Background Atrial fibrillation (AF) has been linked with an increased risk of cognitive impairment and dementia. Purpose To complete a meta-analysis of studies examining the association between AF and cognitive impairment. Data Sources Electronic search of 5 large databases and hand search of article references. Study Selection Prospective and non-prospective studies reporting adjusted risk estimates for the relationship between AF and cognitive impairment. Data Extraction Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality. Data Synthesis Twenty one studies were included in the meta-analysis. AF was significantly associated with a higher risk of cognitive impairment independent of stroke history (relative risk (RR) [95% confidence interval (CI)] =1.34 [1.13, 1.58]), in patients with first-ever or recurrent stroke (RR [95%] =2.7 [1.82, 4.00]) and in a broader population including patients with or without a history of stroke (RR [95% CI] =1.4 [1.19, 1.64]). However, there was significant heterogeneity among studies of the broader population (I2 =69.4 %). Limiting the analysis to prospective studies yielded similar results (RR [95% CI] =1.36 [1.12, 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P value =0.137) but did not alter the pooled estimate substantially (RR [95% CI] = 1.38 [1.22, 1.56]). Limitations There is an inherent bias due to confounding variables in observational studies. There was significant heterogeneity among included studies. Conclusions Evidence suggests that AF is associated with a higher risk of cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the relationship between AF and subtypes of dementia as well as the etiology of cognitive impairment. PMID:23460057
Pothier, Kristell; Morello, Remy; Lelong-Boulouard, Véronique; Lescure, Pascale; Bocca, Marie-Laure; Marcelli, Christian; Descatoire, Pablo; Chavoix, Chantal
Background: Polypharmacy is a well-established risk factor for falls, and these are one of the major health problems that affect the quality of life as people age. However, the risk of mobility and cognitive impairments consecutive to polypharmacy has been little addressed, despite the association between these adverse outcomes and falls. Moreover, the rare polypharmacy cut-offs were all but one arbitrarily determined. Objective: Studying relationships between polypharmacy and both mobility and cognitive impairments, and statistically determining a cut-off point in the number of medicinal molecule beyond which polypharmacy has deleterious consequences with respect to mobility and cognitive impairment. Methods: We enrolled 113 community-dwelling adults aged 55 years and older with a fall history, with or without injury, in the previous year. We carefully collected information about daily medicinal molecules taken. We assessed basic mobility and global cognition with the Time-Up-and-Go and the Montreal Cognitive Assessment (MoCA) test, respectively (clinicaltrials.gov NCT02292316). Results: Timed-Up and Go test and MoCA scores were both significantly correlated with the number of molecule, used. Receiver Operating Characteristic curves indicate, with high prediction (p < 0.002), that daily consumption of five or more molecules is associated with risk for both impaired mobility and global cognition. These relationships were independent of the number of comorbidities and of the pharmacological class. Conclusion: Community-dwelling adults aged 55 years and older who take five or more daily medicinal molecules are at high risk for both mobility and cognitive impairments. Physicians and patients should be aware of these new findings, especially when there are multiple prescribers involved in the care of the patient. PMID:27630572
Vega, Jennifer N.; Newhouse, Paul A.
Mild cognitive impairment (MCI) is widely regarded as the intermediate stage of cognitive impairment between the changes seen in normal cognitive aging and those associated with dementia. Elderly patients with MCI constitute a high-risk population for developing dementia, in particular Alzheimer’s disease (AD). Although the core clinical criteria for MCI have remained largely unchanged, the operational definition of MCI has undergone several revisions over the course of the last decade and remains an evolving diagnosis. Prognostic implications of this diagnosis are becoming clearer with regard to the risk of progressive cognitive deterioration. Although patients with MCI may represent an optimal target population for pharmacological and non-pharmacological interventions, results from clinical trials have been mixed and a definitive effective treatment remains elusive. This article provides a brief overview of the evolution of the concept of MCI and reviews current diagnostic criteria, the longitudinal course of the disorder, and current and emerging treatments for MCI. PMID:25160795
Bocanegra, Yamile; Trujillo-Orrego, Natalia; Pineda, David
INTRODUCTION. The cognitive disorders in Parkinson's disease (PD) have traditionally been associated with the presence of dementia in later stages of the disease. Recent studies, however, consider that cognitive impairment can appear as of early stages. Knowing the cognitive profile of PD furthers our understanding of the clinical phenotype, making it easier to reach a timely diagnosis and favouring intervention on the symptoms from the initial stages. AIM. To present a review of the literature on mild cognitive impairment (MCI) and dementia associated with PD. DEVELOPMENT. Several studies report that patients with PD who have a prolonged time to progression develop dementia. Yet, there have also been reports claiming that, as of the early stages, patients can present subtle cognitive alterations known as MCI. The initial neuropsychological profile is mainly of a non-amnesic type, characterised by executive dysfunction, alterations affecting attention, operative memory deficit and faulty retrieval of information. When patients develop dementia, disorders will arise in the storage of information, in semantic fluency, and in visuospatial and visuoperceptual skills. Currently there are criteria available for diagnosing the MCI and dementia associated with PD, as well as valid reliable instruments for detecting those disorders. CONCLUSIONS. Cognitive symptoms are frequent in PD. From the initial stages of the disease onwards patients may present MCI that is mainly characterised by a fronto-subcortical cognitive profile, whereas dementia usually develops at later stages, when a pattern of posterior cortical cognitive disorder is also observed.
Choi, Catherine H.; Schoenfeld, Brian P.; Liebelt, David A.; Ferreiro, David; Ferrick, Neal J.; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L.; Terlizzi, Allison M.; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T.; Bell, Aaron J.; McDonald, Thomas V.
Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms. PMID:20039205
Yelland, Gregory W
Much is known about the serious neurological effects of gluten ingestion in coeliac disease patients, such as sporadic ataxia and peripheral neuropathy, although the causal links to gluten are still under debate. However, such disorders are observed in only a small percentage of coeliac patients. Much less is known about the transient cognitive impairments to memory, attention, executive function, and the speed of cognitive processing reported by the majority of patients with coeliac disease. These mild degradations of cognitive functions, referred to as "brain fog," are yet to be formally recognized as a medical or psychological condition. However, subtle tests of cognitive function are measurable in untreated patients with coeliac disease and improve over the first 12 months' therapy with a gluten-free diet. Such deficits also occur in patients with Crohn's disease, particularly in association with systemic inflammatory activity. Thus, cognitive impairments associated with brain fog are psychologically and neurologically real and improve with adherence to a gluten-free diet. There is not yet sufficient evidence to provide a definitive account of the mechanism by which gluten ingestion causes the impairments to cognitive function associated with brain fog, but current evidence suggests that it is more likely that the causal factor is not directly related to exposure to gluten.
Alvarez-Sabín, Jose; Román, Gustavo C
Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.
Barman, Apurba; Chatterjee, Ahana; Bhide, Rohit
Traumatic brain injury (TBI) is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits. PMID:27335510
Barman, Apurba; Chatterjee, Ahana; Bhide, Rohit
Traumatic brain injury (TBI) is among the significant causes of morbidity and mortality in the present world. Around 1.6 million persons sustain TBI, whereas 200,000 die annually in India, thus highlighting the rising need for appropriate cognitive rehabilitation strategies. This literature review assesses the current knowledge of various cognitive rehabilitation training strategies. The entire spectrum of TBI severity; mild to severe, is associated with cognitive deficits of varying degree. Cognitive insufficiency is more prevalent and longer lasting in TBI persons than in the general population. A multidisciplinary approach with neuropsychiatric evaluation is warranted. Attention process training and tasks for attention deficits, compensatory strategies and errorless learning training for memory deficits, pragmatic language skills and social behavior guidance for cognitive-communication disorder, meta-cognitive strategy, and problem-solving training for executive disorder are the mainstay of therapy for cognitive deficits in persons with TBI. Cognitive impairments following TBI are common and vary widely. Different cognitive rehabilitation techniques and combinations in addition to pharmacotherapy are helpful in addressing various cognitive deficits.
Reeta, K H; Singh, Devendra; Gupta, Yogendra K
Alzheimer's disease is a major cause of dementia worldwide. Edaravone, a potent free radical scavenger, is reported to be neuroprotective. The present study was designed to investigate the effect of chronic edaravone administration on intracerebroventricular-streptozotocin (ICV-STZ) induced cognitive impairment in male Wistar rats. Cognitive impairment was developed by single ICV-STZ (3 mg/kg) injection bilaterally on day 1. Edaravone (1, 3 and 10 mg/kg, orally, once daily) was administered for 28 days. Morris water maze and passive avoidance tests were used to assess cognitive functions at baseline and on days 14 and 28. ICV-STZ caused cognitive impairment as evidenced by increased escape latency and decreased time spent in target quadrant in the Morris water maze test and reduced retention latency in the passive avoidance test. STZ caused increase in oxidative stress, cholinesterases, inflammatory cytokines and protein expression of ROCK-II and decrease in protein expression of ChAT. Edaravone ameliorated the STZ-induced cognitive impairment. STZ-induced increase in oxidative stress and increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) were mitigated by edaravone. Edaravone also prevented STZ-induced increased protein expression of ROCK-II. Moreover, edaravone significantly prevented STZ-induced increased activity of cholinesterases in the cortex and hippocampus. The decreased expression of ChAT caused by STZ was brought towards normal by edaravone in the hippocampus. The results thus show that edaravone is protective against STZ-induced cognitive impairment, oxidative stress, cholinergic dysfunction and altered protein expressions. This study thus suggests the potential of edaravone as an adjuvant in the treatment of Alzheimer's disease.
Hugo, Julie; Ganguli, Mary
Symptoms of memory loss are caused by a range of cognitive abilities or a general cognitive decline, and not just memory. Clinicians can diagnose the syndromes of dementia (major neurocognitive disorder) and mild cognitive impairment (mild neurocognitive disorder) based on history, examination, and appropriate objective assessments, using standard criteria such as Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. They can then diagnose the causal subtypes of these syndromes using standard criteria for each of them. Brain imaging and biomarkers are making progress in the differential diagnoses among the different disorders. Treatments are still mostly symptomatic.
Bauer, Isabelle E.; Pascoe, Michaela C.; Wollenhaupt-Aguiar, Bianca; Kapczinski, Flavio; Soares, Jair C.
Objectives Recent studies have pointed to neuroinflammation, oxidative stress and neurotrophic factors as key mediators in the pathophysiology of mood disorders. Little is however known about the cascade of biological episodes underlying the cognitive deficits observed during the acute and euthymic phases of bipolar disorder (BD). The aim of this review is to assess the potential association between cognitive impairment and biomarkers of inflammation, oxidative stress and neurotrophic activity in BD. Methods Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to November 2013, for human studies that collected both inflammatory markers and cognitive data in BD. Selected search terms were bipolar disorder, depression, mania, psychosis, inflammatory, cognitive and neurotrophic. Results Ten human studies satisfied the criteria for consideration. The findings showed that high levels of peripheral inflammatory-cytokine, oxidative stress and reduced brain derived neurotrophic factor (BDNF) levels were associated with poor cognitive performance. The BDNF val66met polymorphism is a potential vulnerability factor for cognitive impairment in BD. Conclusions Current data provide preliminary evidence of a link between the cognitive decline observed in BD and mechanisms of neuroinflammation and neuroprotection. The identification of BD specific inflammatory markers and polymorphisms in inflammatory response genes may be of assistance for therapeutic intervention. PMID:24862657
Moreau, Noémie; Rauzy, Stéphane; Bonnefoi, Bernadette; Renié, Laurent; Martinez-Almoyna, Laurent; Viallet, François; Champagne-Lavau, Maud
Theory of Mind refers to the ability to infer other’s mental states, their beliefs, intentions, or knowledge. To date, only two studies have reported the presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the present study,we evaluated 20 MCI patients and compared them with 25 healthy control participants using two Theory of Mind tasks. The first task was a false belief paradigm as frequently used in the literature, and the second one was a referential communication task,assessing Theory of Mind in a real situation of interaction and which had never been used before in this population. The results showed that MCI patients presented difficulties inferring another person’s beliefs about reality and attributing knowledge to them in a situation of real-life interaction. Two different patterns of Theory of Mind emerged among the patients. In comparison with the control group, some MCI patients demonstrated impairment only in the interaction task and presented isolated episodicmemory impairment, while others were impaired in both Theory of Mind tasks and presented cognitive impairment impacting both episodic memory and executive functioning. Theory of Mind is thus altered in the very early stages of cognitive impairment even in real social interaction, which could impact precociously relationships in daily life.
Brennan, Mark; Horowitz, Amy; Reinhardt, Joann P.; Stuen, Cynthia; Rubio, Roman; Oestreicher, Nina
Age-related macular degeneration (AMD) is the leading cause of legal blindness among persons aged 50 years and older and is most prevalent among individuals of European descent aged 65 and older (Friedman et al., 2004; Rosenthal & Thompson, 2003). By affecting central vision, AMD interferes with such tasks as reading, driving, and activities…
Borges, Sheila de Melo; Radanovic, Márcia; Forlenza, Orestes Vicente
Association between cognitive impairment and gait performance occurs in mild cognitive impairment (MCI) and Alzheimer's disease (AD), particularly under "divided attention" conditions, leading to a greater risk of falls. We studied 36 controls, 42 MCI, and 26 mild AD patients, using the Timed Up-and-Go test (TUG) under four conditions: TUG single - TUG1; TUG cognitive - TUG2; TUG manual -TUG3; TUG cognitive and manual - TUG4. Cognition was assessed using the MMSE, SKT, Exit25, and TMT (A and B). We found significant correlations between cognitive scores and TUG2 [r values (MMSE: -0.383, TMT-A: 0.430, TMT-B: 0.386, Exit25: 0.455, SKT: 0.563)] and TUG4 [(MMSE: -0.398, TMT-A: 0.384, TMT-B: 0.352,Exit25: 0.466, SKT: 0.525)] in the AD group, and between all TUG modalities and SKT in MCI and AD. Our results revealed that functional mobility impairment in cognitive dual tasks correlated to cognitive decline in AD patients and to attention and memory impairment in MCI.
Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y
Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.
McQuail, Joseph A; Beas, B Sofia; Kelly, Kyle B; Simpson, Kailey L; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L
Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory. Experiments herein show that working memory depends on NR2A- but not NR2B-NMDARs in PFC of rats and that NR2A-NMDARs mediate the majority of evoked NMDAR currents on layer 2/3 PFC pyramidal neurons. Moreover, attenuated expression of the NR2A but not the NR2B subunit in PFC associates with naturally occurring working memory impairment in aged rats. Finally, NMDAR currents and working memory are enhanced in aged rats by promoting activation of the NR2A-enriched synaptic pool of PFC NMDARs. These results implicate NR2A-NMDARs in normal working memory and suggest novel treatment strategies for improving working memory in cognitive disorders.
Ebert, Kerry Danahy; Rentmeester-Disher, Jill; Kohnert, Kathryn
Substantial evidence points to the presence of subtle weaknesses in the nonlinguistic cognitive processing skills of children with primary (or specific) language impairment (PLI). It is possible that these weaknesses contribute to the language learning difficulties that characterize PLI, and that treating them can improve language skills. To test…
Blieszner, Rosemary; Roberto, Karen A.
Purpose: We examined characteristics, responses, and psychological well-being of care partners who support and assist older adults recently diagnosed with mild cognitive impairment (MCI). Design and Methods: Based on a sample of 106 care partners of community residents diagnosed with MCI at memory clinics, we conducted face-to-face interviews…
Lee, Kang Soo; Cheong, Hae-Kwan; Kim, Eun A; Kim, Kyung Ran; Oh, Byoung Hoon; Hong, Chang Hyung
The purpose of this study was to determine the relationship between nutritional risk and cognitive impairment in the elderly living in the community. Data obtained from 2934 subjects (912 men and 2022 women) aged above 60 years was analyzed from the Gwangju Dementia and Mild Cognitive Impairment Study (GDEMCIS). The study questionnaire comprised demographic characteristics, history of current and past illnesses, drug history, Korean version-Mini Mental State Examination (K-MMSE), and Nutritional Screening Initiative (NSI) checklist. Additionally, we examined the blood pressure, fasting serum glucose level, lipid profile, body mass index, and ApoE genotype. Of the total, 1942 (66.2%) demonstrated good nutritional state (NSI checklist score< or =2) and 992 (33.8%) were at moderate or high nutritional risk (NSI checklist score>2). Multiple logistic regression analysis revealed that moderate or high nutritional risk subjects were associated with an increased risk of cognitive impairment (K-MMSE score< or =17) after adjustment for age, sex, educational level, and Korean version of Short form Geriatric Depression Scale (K-SGDS) score (Odds ratio=OR=1.71, 95%; confidence interval=CI=1.17-2.50). These results suggest that nutritional risk may be associated with cognitive impairment in the elderly.
Helvink, Badalin; Holroyd, Suzanne
Repetitive and stereotypic behavioral disturbances in patients with dementia are common; however, little is known regarding successful treatments. The authors describe six cases of elderly cognitively impaired patients exhibiting repetitive and stereotypic behaviors who were treated successfully with buspirone. The cases demonstrate that buspirone may be an effective and safe treatment for patients with dementia who demonstrate repetitive and stereotypic behavior disorders.
Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.
Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…
Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome…
Ladeira, Rodolfo B.; Diniz, Breno S.; Nunes, Paula V.; Forlenza, Orestes V.
OBJECTIVE To determine the accuracy of the Mini-Mental State Examination combined with the Verbal Fluency Test and Clock Drawing Test for the identification of patients with mild cognitive impairment and Alzheimer’s disease (AD). METHOD These tests were used to evaluate cognitive function in 247 older adults. Subjects were divided into three groups according to their cognitive state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired controls (n=83), based on clinical and neuropsychological data. The diagnostic accuracy of each test for discriminating between these diagnostic groups (mild cognitive impairment or AD vs. controls) was examined with the aid of Receiver Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of the combination of tests on diagnostic accuracy. RESULTS Although they were accurate enough for the identification of Alzheimer’s disease, neither test alone proved adequate for the correct separation of patients with mild cognitive impairment from healthy subjects. Combining these tests did not improve diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in the identification of patients with mild cognitive impairment or Alzheimer’s disease. CONCLUSIONS The present data do not warrant the combined use of the Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test as a sufficient diagnostic schedule in screening for mild cognitive impairment. The present data do not support the notion that the combination of test scores is better that the use of Mini-Mental State Examination scores alone in the screening for Alzheimer’s disease. PMID:19841703
Sun, Li; Xie, Keliang; Zhang, Changsheng; Song, Rui; Zhang, Hong
Cognitive decline after surgery in the elderly population is a major clinical problem with high morbidity. Hyperbaric oxygen (HBO) preconditioning can induce significant neuroprotection against acute neurological injury. We hypothesized that HBO preconditioning would prevent the development of postoperative cognitive impairment. Elderly male rats (20 months old) underwent stabilized tibial fracture operation under general anesthesia after HBO preconditioning (once a day for 5 days). Separate cohorts of animals were tested for cognitive function with fear conditioning and Y-maze tests, or euthanized at different times to assess the blood-brain barrier integrity, systemic and hippocampal proinflammatory cytokines, and caspase-3 activity. Animals exhibited significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after surgery, which were significantly prevented by HBO preconditioning. Furthermore, HBO preconditioning significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1 β (IL-1β), IL-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, HBO preconditioning markedly improved blood-brain barrier integrity and caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that HBO preconditioning could significantly mitigate surgery-induced cognitive impairment, which is strongly associated with the reduction of systemic and hippocampal proinflammatory cytokines and caspase-3 activity.
López Mongil, Rosa; López Trigo, José Antonio
Because of the substantial increase in population ageing, age-related processes, such as dementia and Alzheimer disease (AD), are becoming highly prevalent. The course of this disease, including preprodromic phases, lasts at least 20 years. The presence of comorbidities, especially those of vascular origin, can trigger and aggravate disease progression. On the other hand, cognitive reserve, the absence or control of comorbid factors and healthy lifestyles can protect or modify -in the sense of slow down- disease progression. Knowledge of the phases of AD and their functional impact on affected individuals helps to identify the average prognosis and, in particular, to establish and predict care plans based on the individual's needs.
Kapogiannis, Dimitrios; Mattson, Mark P.
Summary Epidemiological, neuropathological and functional neuroimaging evidence implicates global and regional derangements in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified adaptively by excitatory and inhibitory synaptic activity and neurotrophic factors. Aging and Alzheimer’s disease (AD) cause perturbations in cellular energy metabolism, level of excitation/inhibition and neurotrophic factor release that overwhelm compensatory mechanisms and result in neuronal microcircuit and brain network dysfunction. A prolonged positive energy balance impairs the ability of neurons to respond adaptively to oxidative and metabolic stress. Experimental studies in animals demonstrate how derangements related to chronic positive energy balance, such as diabetes, set the stage for accelerated cognitive aging and AD. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signaling) have shown efficacy in animal models and preliminary studies in humans. PMID:21147038
Dulau, Cecile; Deloire, Mathilde; Diaz, Helene; Saubusse, Aurore; Charre-Morin, Julie; Prouteau, Antoinette; Brochet, Bruno
The objective of this study is to evaluate the relationship between social cognition (SC) and cognitive impairment in persons with multiple sclerosis (PwMS). A prospective study was conducted in 60 PwMS, 30 with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS) and 15 with primary progressive MS (PPMS), and in healthy subjects (HS). All subjects were assessed by the Bordeaux Social Cognition Evaluation Protocol (PECS-B) (facial emotion recognition, theory of mind, emotional awareness and cognitive and affective alexithymia), by a large neuropsychological battery and by questionnaires (depression and anxiety). 43.3% of PwMS were impaired for at least one SC test. The proportion of PwMS with at least two impaired SC tests was similar in all three phenotypes (20%). Mean scores differed significantly between PwMS and HS only for the Reading the Mind in the Eyes Test, a test of Theory of Mind (ToM). ANOVA analyses showed an effect of phenotype on emotional awareness scores with lower scores in PPMS as compared to RRMS. ToM performance was significantly correlated (r (2) = 0.56) with executive functions, working memory and episodic memory scores. SC impairment was found in all phenotypes and was more prominent in cognitively impaired MS patients. Executive functions, and working and episodic memory performance accounts for approximately 50% of ToM performance. Emotional awareness is more impaired in progressive MS.
Joubert, Sven; Brambati, Simona M.; Ansado, Jennyfer; Barbeau, Emmanuel J.; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Celine; Kergoat, Marie-Jeanne
Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to…
Liu, Qing; Zhu, Zude; Teipel, Stefan J; Yang, Jianwei; Xing, Yi; Tang, Yi; Jia, Jianping
Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders.
Liu, Qing; Zhu, Zude; Teipel, Stefan J.; Yang, Jianwei; Xing, Yi; Tang, Yi; Jia, Jianping
Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders. PMID:28289381
Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen
Approximately five million people suffer with Alzheimer's disease (AD) and more than twenty-four million people are diagnosed with AD, pre-senile dementia, and other disorders of cognitive loss worldwide. Furthermore, the annual cost per patient with AD can approach $200,000 with an annual population aggregate cost of $100 billion. Yet, complete therapeutic prevention or reversal of neurovascular injury during AD and cognitive loss is not achievable despite the current understanding of the cellular pathways that modulate nervous system injury during these disorders. As a result, identification of novel therapeutic targets for the treatment of neurovascular injury would be extremely beneficial to reduce or eliminate disability from diseases that lead to cognitive loss or impairment. Here we describe the capacity of intrinsic cellular mechanisms for the novel pathways of erythropoietin and forkhead transcription factors that may offer not only new strategies for disorders such as AD and cognitive loss, but also function as biomarkers for disease onset and progression.
EBERT, KERRY DANAHY; RENTMEESTER-DISHER, JILL; KOHNERT, KATHRYN
Substantial evidence points to the presence of subtle weaknesses in the nonlinguistic cognitive processing skills of children with primary (or specific) language impairment (PLI). It is possible that these weaknesses contribute to the language learning difficulties that characterize PLI, and that treating them can improve language skills. To test this premise, we treated two nonlinguistic cognitive processing skills, processing speed and sustained selective attention, in two Spanish–English bilingual children with PLI. The study followed a single-subject multiple baseline design, with both repeated measures and standardized pre- and post-testing as outcome measures. Results from the repeated measures tasks showed that both participants made gains in nonlinguistic cognitive processing skills as well as in Spanish and English. These results both replicate and extend prior work showing that non-linguistic cognitive processing treatment can positively affect language skills in children with PLI. PMID:22540358
Chan, Phillip; Hellmuth, Joanna; Spudich, Serena; Valcour, Victor
The implementation of combination antiretroviral therapy (cART) has changed HIV infection into a chronic illness, conveying extensive benefits, including greater longevity and advantages for the central nervous system (CNS). However, studies increasingly confirm that the CNS gains are incomplete, with reports of persistent immune activation affecting the CNS despite suppression of plasma HIV RNA. The rate of cognitive impairment is unchanged, although severity is generally milder than in the pre-cART era. In this review, we discuss cognitive outcomes from recently published clinical HIV studies, review observations on HIV biomarkers for cognitive change, and emphasize longitudinal imaging findings. Additionally, we summarize recent studies on CNS viral invasion, CD8 encephalitis, and how CNS involvement during the earliest stages of infection may set the stage for later cognitive manifestations.
Sellaro, Roberta; Colzato, Lorenza S
The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI) is associated with frontal lobe dysfunction and cognitive deficits concerning mental flexibility and inhibitory control efficiency. The present study aims at replicating and extending these observations. We compared cognitive control performance of normal weight (BMI < 25) and overweight (BMI ≥ 25) university students on a task tapping either inhibitory control (Experiment 1) or interference control (Experiment 2). Experiment 1 replicated previous findings that found less efficient inhibitory control in overweight individuals. Experiment 2 complemented these findings by showing that cognitive control impairments associated with high BMI also extend to the ability to resolve stimulus-induced response conflict and to engage in conflict-driven control adaptation. The present results are consistent with and extend previous literature showing that high BMI in young, otherwise healthy individuals is associated with less efficient cognitive control functioning.
Reis, Patricia A.; Estato, Vanessa; da Silva, Tathiany I.; d'Avila, Joana C.; Siqueira, Luciana D.; Assis, Edson F.; Bozza, Patricia T.; Bozza, Fernando A.; Tibiriça, Eduardo V.; Zimmerman, Guy A.; Castro-Faria-Neto, Hugo C.
Cerebral malaria (CM) is the most severe manifestation of Plasmodium falciparum infection in children and non-immune adults. Previous work has documented a persistent cognitive impairment in children who survive an episode of CM that is mimicked in animal models of the disease. Potential therapeutic interventions for this complication have not been investigated, and are urgently needed. HMG-CoA reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. In addition to their effects on the inhibition of cholesterol synthesis, statins have pleiotropic immunomodulatory activities. Here we tested if statins would prevent cognitive impairment in a murine model of cerebral malaria. Six days after infection with Plasmodium berghei ANKA (PbA) mice displayed clear signs of CM and were treated with chloroquine, or chloroquine and lovastatin. Intravital examination of pial vessels of infected animals demonstrated a decrease in functional capillary density and an increase in rolling and adhesion of leukocytes to inflamed endothelium that were reversed by treatment with lovastatin. In addition, oedema, ICAM-1, and CD11b mRNA levels were reduced in lovastatin-treated PbA-infected mice brains. Moreover, HMOX-1 mRNA levels are enhanced in lovastatin-treated healthy and infected brains. Oxidative stress and key inflammatory chemokines and cytokines were reduced to non-infected control levels in animals treated with lovastatin. Fifteen days post-infection cognitive dysfunction was detected by a battery of cognition tests in animals rescued from CM by chloroquine treatment. In contrast, it was absent in animals treated with lovastatin and chloroquine. The outcome was similar in experimental bacterial sepsis, suggesting that statins have neuroprotective effects in severe infectious syndromes in addition to CM. Statin treatment prevents neuroinflammation and blood brain barrier dysfunction in experimental CM and related conditions that are associated with
Tkaczynska, Zuzanna; Pilotto, Andrea; Becker, Sara; Gräber-Sultan, Susanne; Berg, Daniela; Liepelt-Scarfone, Inga
Urinary dysfunction (UD) is a common non-motor feature of Parkinson's disease (PD), and might be secondary to neurodegeneration involving cortical and subcortical brain areas. The possible link between UD and cognitive deficits has never been examined in frontal cortex impairment, and is still not completely understood in PD. In the present study, 94 PD patients underwent a comprehensive motor, cognitive and non-motor assessment. It was shown that 55.3% of patients reported UD, of which 17% needed specific urological treatment. Patients who reported UD performed worse on global cognition (PANDA, p = .05), visuo-constructive functions (CERAD/praxis, p = .03; and Figure Test, p = .03), and instrumental activities of daily living functions (IADL, p = .03), than patients without UD. The group with UD medication performed worse on global cognition (PANDA, p = .02) and visuo-constructive functions (CERAD/praxis, p = .05; CERAD/praxis recall, p = .05) than the UD group without medication, independent of anticholinergic treatment effect. Our findings suggest an association between cognitive impairment and UD in PD independent from symptomatic treatment.
Rise, Ida Vikan; Haro, Josep Maria; Gjervan, Bjørn
Introduction Data specific to late-life bipolar disorder (BD) are limited. Current research is sparse and present guidelines are not adapted to this group of patients. Objectives We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late-life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment. Methods Eligible studies were identified in MedLine by the Medical Subject Headings terms “bipolar disorder” and “aged”. We only included original research reports published in English between 2012 and 2015. Results From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age-matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested. Conclusion There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that this group needs an adapted clinical assessment and specific clinical guidelines need to be established. PMID:27274256
Voytek, Bradley; Kramer, Mark A; Case, John; Lepage, Kyle Q; Tempesta, Zechari R; Knight, Robert T; Gazzaley, Adam
Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <-1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in
Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...
Josephs, Keith A; Murray, Melissa E; Tosakulwong, Nirubol; Whitwell, Jennifer L; Knopman, David S; Machulda, Mary M; Weigand, Stephen D; Boeve, Bradley F; Kantarci, Kejal; Petrucelli, Leonard; Lowe, Val J; Jack, Clifford R; Petersen, Ronald C; Parisi, Joseph E; Dickson, Dennis W
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies. TDP-43 inclusion when present were rare and predominantly perivascular. Of the 15 with TDP-43, three showed a moderate number of inclusions and also had hippocampal sclerosis, neuronal intranuclear inclusions and fine neurites of the CA1 region of the hippocampus. Four cases (8%) had an apolipoprotein epsilon 4 (APOE4) allele. There was a significant correlation between age at death and Braak NFT stage (r = 0.32, p = 0.02). After accounting for age at clinical examination, there were significant associations between Braak NFT stage, and WAIS-R Block Design and Trail Making Tests A and B, with higher Braak stage associated with poorer performances. Thirty of the 52 cases had completed an antemortem volumetric head MRI. Two separate MRI analyses revealed an association between higher Braak NFT stage and grey matter atrophy in the head of the left hippocampus. There were no significant clinical or radiologic associations with TDP-43. Findings from this study demonstrate that aggregated tau distribution is associated with poorer cognitive performance, as well as atrophy, in the absence of beta-amyloid. These findings support the parcellation of definite PART as a useful construct. The relatively low frequencies of APOE4, TDP-43, Lewy bodies, and hippocampal sclerosis, and the rarity and morphology of TDP-43 lesions are noted contrasts to what is typically observed in Alzheimer's disease of the old.
Breau, Lynn M; Camfield, Carol S; McGrath, Patrick J; Finley, G Allen
Diagnosing cause of pain in children with severe cognitive impairments is difficult due to their problems with communication. Identification of risk factors for specific pain etiologies might help professionals in this task. The aim of this study was to determine whether child-related characteristics increase risk for specific types of pain. Participants were the caregivers of 41 females and 53 males with moderate to profound mental retardation, who were aged 3 to 18 years 8 months (mean 10:1, SD 4:4) but who communicated at the level of a typical child of 13.8 months (SD 10 months): 44 of the children had cerebral palsy (CP) and 59 a seizure disorder. Caregivers reported the cause of children's episodes of pain for four 1-week periods over 1 year. Logistic regression analyses were used to predict occurrence of specific types of pain using children's demographic, medical, and physical characteristics. Children had 406 episodes of pain due to accident, gastrointestinal conditions, musculoskeletal problems, infection, recurrent conditions, and common childhood causes. Results indicated that a unique set of risk factors predicted each pain type in this sample. Significant risk factors for pain included: lack of visual impairment and leg impairment (accidental pain); seizures, leg impairment, and greater number of medications (non-accidental pain); being male and tube fed (musculoskeletal pain); age <7 years, absence of CP, visual impairment, and less frequent medical monitoring (infection pain); being female and with arm impairment (gastrointestinal pain); and being tube fed and taking fewer medications (common childhood pains). In most cases, models were more specific than sensitive, indicating that the significant predictors are more useful for eliminating potential pain causes. These results suggest that population risk factors may be helpful in structuring diagnostic investigations for individual children with severe cognitive impairments.
Vinogradov, Sophia; Fisher, Melissa; de Villers-Sidani, Etienne
Neuropsychiatric illnesses are associated with dysfunction in distributed prefrontal neural systems that underlie perception, cognition, social interactions, emotion regulation, and motivation. The high degree of learning-dependent plasticity in these networks-combined with the availability of advanced computerized technology-suggests that we should be able to engineer very specific training programs that drive meaningful and enduring improvements in impaired neural systems relevant to neuropsychiatric illness. However, cognitive training approaches for mental and addictive disorders must take into account possible inherent limitations in the underlying brain 'learning machinery' due to pathophysiology, must grapple with the presence of complex overlearned maladaptive patterns of neural functioning, and must find a way to ally with developmental and psychosocial factors that influence response to illness and to treatment. In this review, we briefly examine the current state of knowledge from studies of cognitive remediation in psychiatry and we highlight open questions. We then present a systems neuroscience rationale for successful cognitive training for neuropsychiatric illnesses, one that emphasizes the distributed nature of neural assemblies that support cognitive and affective processing, as well as their plasticity. It is based on the notion that, during successful learning, the brain represents the relevant perceptual and cognitive/affective inputs and action outputs with disproportionately larger and more coordinated populations of neurons that are distributed (and that are interacting) across multiple levels of processing and throughout multiple brain regions. This approach allows us to address limitations found in earlier research and to introduce important principles for the design and evaluation of the next generation of cognitive training for impaired neural systems. We summarize work to date using such neuroscience-informed methods and indicate some
Uguccioni, Ginevra; Lavault, Sophie; Chaumereuil, Charlotte; Golmard, Jean-Louis; Gagnon, Jean-François; Arnulf, Isabelle
Study Objectives: In Kleine-Levin syndrome (KLS), episodes of hypersomnia, cognitive, and behavioral disturbances alternate with asymptomatic periods. Because 50% of patients report decreased academic performances, we evaluated their cognitive status during asymptomatic periods, determinants of deficits, and changes during follow-up. Methods: The cognitive assessment during asymptomatic periods in all consecutive patients with typical KLS and healthy controls included the non-verbal intelligence quotient (Raven Progressive Matrices), the Trail Making Test, the Stroop Color-Word Test, the Wechsler Memory Test, verbal fluencies, the Free and Cued Learning Memory Test, and the Rey-Osterreith Complex Figure. Cognitive status was reevaluated after 0.5 to 2 y in 44 patients. Results: At baseline, compared with the 42 controls, the 122 patients with KLS exhibited lower non-verbal intelligence quotient, speed of processing, attention, and reduced retrieval strategies in episodic memory. Higher episode frequency, shorter episode duration, shorter time since last episode, deeper sleep, and megaphagia during episodes predicted impaired memory. The visuoconstructional abilities and non-verbal memory were intact. After a mean follow-up of 1.7 ± 1.0 y, the episode frequency decreased from 4.6 ± 4.8 to 1.7 ± 1.9/y. The logical reasoning and attention improved, the processing speed remained low, and the retrieval strategies in verbal memory further worsened. Conclusions: In this field study, one-third of patients with KLS have long-term cognitive deficits affecting retrieval and processing speed. Cognitive function should be systematically tested in patients with KLS, which appears important to help patients in their academic studies. Citation: Uguccioni G, Lavault S, Chaumereuil C, Golmard JL, Gagnon JF, Arnulf I. Long-term cognitive impairment in kleine-levin syndrome. SLEEP 2016;39(2):429–438. PMID:26414895
Vinogradov, Sophia; Fisher, Melissa; de Villers-Sidani, Etienne
Neuropsychiatric illnesses are associated with dysfunction in distributed prefrontal neural systems that underlie perception, cognition, social interactions, emotion regulation, and motivation. The high degree of learning-dependent plasticity in these networks—combined with the availability of advanced computerized technology—suggests that we should be able to engineer very specific training programs that drive meaningful and enduring improvements in impaired neural systems relevant to neuropsychiatric illness. However, cognitive training approaches for mental and addictive disorders must take into account possible inherent limitations in the underlying brain ‘learning machinery' due to pathophysiology, must grapple with the presence of complex overlearned maladaptive patterns of neural functioning, and must find a way to ally with developmental and psychosocial factors that influence response to illness and to treatment. In this review, we briefly examine the current state of knowledge from studies of cognitive remediation in psychiatry and we highlight open questions. We then present a systems neuroscience rationale for successful cognitive training for neuropsychiatric illnesses, one that emphasizes the distributed nature of neural assemblies that support cognitive and affective processing, as well as their plasticity. It is based on the notion that, during successful learning, the brain represents the relevant perceptual and cognitive/affective inputs and action outputs with disproportionately larger and more coordinated populations of neurons that are distributed (and that are interacting) across multiple levels of processing and throughout multiple brain regions. This approach allows us to address limitations found in earlier research and to introduce important principles for the design and evaluation of the next generation of cognitive training for impaired neural systems. We summarize work to date using such neuroscience-informed methods and indicate
Elder, Gregory A
Traumatic brain injury (TBI) is a common cause of morbidity and mortality in military life. Interest in military TBI has increased recently due to the conflicts in Iraq and Afghanistan. Certain types of TBI are relatively unique to the military, the most prominent being blast-related TBI. Blast-related mild TBI has been of particular concern in veterans from the most recent conflicts although controversy remains concerning its separation from post-traumatic stress disorder. TBI is also a risk factor for the later development of neurodegenerative diseases in which cognitive impairment is prominent putting veterans at risk for disorders including Alzheimer's disease and chronic traumatic encephalopathy. Recent evidence associating TBI with chronic cognitive impairment is reviewed in the context of its relevance to military veterans.
The takeaway message of this advancing science surrounding the causes and treatment of neurodegenerative diseases is to recognize MCI symptoms early and intervene with a comprehensive, multifaceted, personalized lifestyle medicine program that is designed to improve neurological function and built on the components described above. The present evidence suggests this approach represents the best medicine available today for beating back the rising tide of cognitive impairment and neurodegeneration. PMID:27330484
Hugo, Julie; Ganguli, Mary
Synopsis Clinicians can diagnose the syndromes of dementia (major neurocognitive disorder) and mild cognitive impairment (mild neurocognitive disorder) based on history, examination, and appropriate objective assessments, using standard criteria such as DSM-5. They can then diagnose the etiological subtypes of these syndromes using standard criteria for each of them. Brain imaging and biomarkers are gaining ground for the differential diagnoses among the different disorders. Treatments for the most part are still symptomatic. PMID:25037289
Fortier-Brochu, Émilie; Morin, Charles M.
Study Objectives: The aims of this study were to (1) investigate the nature of cognitive impairment in individuals with insomnia, (2) document their clinical significance, (3) examine their correlates, and (4) explore differences among individuals with insomnia with and without cognitive complaints. Design: Participants underwent 3 consecutive nights of polysomnography. On the morning following the third night, they completed a battery of questionnaires and neuropsychological tests. Participants: The sample included 25 adults with primary insomnia (mean age: 44.4 ± 11.5 y, 56% women) and 16 controls (mean age: 42.8 ± 12.9 y, 50% women) matched for sex, age, and education. Intervention: N/A. Measurement and Results: Participants completed neuropsychological tests covering attention, memory, working memory, and executive functions, as well as questionnaires assessing the subjective perception of performance, depression, anxiety, fatigue, sleepiness, and hyperarousal. There were significant group differences for the attention and episodic memory domains. Clinically significant deficits were more frequent in the insomnia group. Within the insomnia group, individuals with cognitive complaints exhibited significantly poorer performance on a larger number of neuropsychological variables. All impaired aspects of performance were significantly associated with either subjective or objective sleep continuity, and some were also independently related to sleep microstructure (i.e., relative power for alpha frequencies) or selected psychological variables (i.e., beliefs or arousal). Conclusions: These findings suggest clinically significant alterations in attention and episodic memory in individuals with insomnia. Objective deficits were more pronounced and involved more aspects of performance in a subgroup of individuals with cognitive complaints. These deficits appear associated with sleep continuity, and may also be related to sleep microstructure and dysfunctional beliefs
Gill, Nigel; Hammond, Simon; Cross, Jane; Smith, Toby; Lambert, Nigel; Fox, Chris
The global shift in demographics towards aging populations is leading to a commensurate increase in age-related disease and frailty. It is essential to optimise health services to meet current needs and prepare for anticipated future demands. This paper explores issues impacting on people living with cognitive impairment and/or dementia who experience a hip fracture and are cared for in acute settings. This is important given the high mortality and morbidity associated with this population. Given the current insufficiency of clear evidence on optimum rehabilitation of this patient group, this paper explored three key themes namely: recognition of cognitive impairment, response by way of training and education of staff to optimise care for this patient group and review of the importance of outcomes measures. Whilst there is currently insufficient evidence to draw conclusions about the optimal ways of caring for patients living with dementia following hip fracture, this paper concludes that future research should improve understanding of healthcare staff education to improve the outcomes for this important group of patients.
Lindau, Maria; Bjork, Randall
Aims To evaluate the occurrence of anosognosia (lack of awareness) and anosodiaphoria (insouciance) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and to evaluate the influence of a worsening of dementia on these phenomena. Methods A self-evaluation scale was used assessing degrees of anosognosia and anosodiaphoria; furthermore, a neuropsychological assessment and statistical analyses with nonparametric tests which could cope with data on an ordinal scale level and small samples were employed. Results Cognitive ability was lower in AD (n = 9) than in MCI patients (n = 12), but AD patients self-rated lower cognitive disabilities, which is interpreted as one relative sign of anosognosia in AD. Awareness of the reasons for cognitive problems was also lower in AD, which is considered as another sign of anosognosia. The main pattern in MCI found that the higher the awareness, the lower the cognitive ability. In AD low awareness paralleled low cognitive functioning. Anosodiaphoria was present in AD but not in MCI. Conclusion According to the literature anosognosia and anosodiaphoria seem to increase with progression of dementia from MCI as a result of right hemispheric alterations. PMID:25759713
Moebs, Isabelle; Gee, Susan; Miyahara, Motohide; Paton, Helen; Croucher, Matthew
Cognitive rehabilitation has been developed to improve quality of life, activities of daily living and mood for people with cognitive impairment, but the voice of people with cognitive impairment has been underrepresented. This study aimed to understand the experience of people living with cognitive impairment, as well as their caregivers who took part in a cognitive rehabilitation intervention programme. Twelve individuals with cognitive impairment and 15 caregivers participated in individual qualitative interviews. The interview data were analysed in three steps: 1) familiarisation of the transcripts; 2) identification of themes; 3) re-interpretation, refinement and integration of themes with methodological auditors. Both participants living with cognitive impairment and caregivers valued the comfortable environment with friendly, caring and supportive group leaders who taught practical tips and strategies. The participants living with cognitive impairment enjoyed socialising with like others. Caregivers benefited from learning about memory problems and sharing their challenges with other caregivers. The participants living with cognitive impairment emphasised the benefits of relational and practical aspects, whereas the caregivers valued the informational and emotional support. In conclusion, both participants living with cognitive impairment and caregivers found the cognitive rehabilitation group useful.
Wisse, Laura E M; Butala, Nirali; Das, Sandhitsu R; Davatzikos, Christos; Dickerson, Bradford C; Vaishnavi, Sanjeev N; Yushkevich, Paul A; Wolk, David A
We aim to better characterize mild cognitive impairment (MCI) patients with suspected non-Alzheimer's disease (AD) pathology (SNAP) based on their longitudinal outcome, cognition, biofluid, and neuroimaging profile. MCI participants (n = 361) from ADNI-GO/2 were designated "amyloid positive" with abnormal amyloid-beta 42 levels (AMY+) and "neurodegeneration positive" (NEU+) with abnormal hippocampal volume or hypometabolism using fluorodeoxyglucose-positron emission tomography. SNAP was compared with the other MCI groups and with AMY- controls. AMY-NEU+/SNAP, 16.6%, were older than the NEU- groups but not AMY- controls. They had a lower conversion rate to AD after 24 months than AMY+NEU+ MCI participants. SNAP-MCI participants had similar amyloid-beta 42 levels, florbetapir and tau levels, but larger white matter hyperintensity volumes than AMY- controls and AMY-NEU- MCI participants. SNAP participants performed worse on all memory domains and on other cognitive domains, than AMY-NEU- participants but less so than AMY+NEU+ participants. Subthreshold levels of cerebral amyloidosis are unlikely to play a role in SNAP-MCI, but pathologies involving the hippocampus and cerebrovascular disease may underlie the neurodegeneration and cognitive impairment in this group.
Lugnegård, Tove; Unenge Hallerbäck, Maria; Hjärthag, Fredrik; Gillberg, Christopher
Social cognition impairments are well described in both autism spectrum disorders, including Asperger syndrome (AS), and in schizophrenia spectrum disorders. However, little is known about whether there are differences between the two groups of disorders regarding this ability. The aim of this study was to compare social cognition abilities in AS and schizophrenia. Fifty-three individuals (26 men, 27 women) with a clinical diagnosis of AS, 36 (22 men, 14 women) with a clinical diagnosis of schizophrenic psychosis, and 50 non-clinical controls (19 men, 31 women) participated in the study. Clinical diagnoses were confirmed either by Structured Clinical Interview on DSM-IV diagnosis or the Diagnostic Interview for Social and Communication Disorders. Verbal ability was assessed using the Vocabulary subtest of the WAIS-III. Two social cognition instruments were used: Reading the Mind in the Eyes Test (Eyes Test) and the Animations Task. On the Eyes Test, patients with schizophrenia showed poorer results compared to non-clinical controls; however, no other group differences were seen. Both clinical groups scored significantly lower than the comparison group on the Animations Task. The AS group performed somewhat better than the schizophrenia group. Some differences were accounted for by gender effects. Implicit social cognition impairments appear to be at least as severe in schizophrenia as they are in AS. Possible gender differences have to be taken into account in future research on this topic.
Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T
There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.
Geda, Yonas E; Nedelska, Zuzana
The field of aging and dementia is increasingly preoccupied with identification of the asymptomatic phenotype of Alzheimer disease (AD). A quick glance at historical landmarks in the field indicates that the agenda and priorities of the field have evolved over time. The initial focus of research was dementia. In the late 1980s and 1990s, dementia researchers reported that some elderly persons are neither demented nor cognitively normal. Experts coined various terms to describe the gray zone between normal cognitive aging and dementia, including mild cognitive impairment. Advances made in epidemiologic, neuroimaging, and biomarkers research emboldened the field to seriously pursue the avenue of identifying asymptomatic AD. Accurate "diagnosis" of the phenotype has also evolved over time. For example, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Task Force is contemplating to use the terms major and minor neurocognitive disorders. The six papers published in this edition of the journal pertain to mild cognitive impairment, which is envisaged to become a subset of minor neurocognitive disorders. These six studies have three points in common: 1) All of them are observational studies; 2) they have generated useful hypotheses or made important observations without necessarily relying on expensive biomarkers; and 3) Based on the new National Institute on Aging and the Alzheimer's Association guidelines, all the studies addressed the symptomatic phase of AD. Questionnaire-based observational studies will continue to be useful until such a time that validated biomarkers, be it chemical or neuroimaging, become widely available and reasonably affordable.
Uttner, I; Weber, S; Freund, W; Schmitz, B; Ramspott, M; Huber, R
Transient global amnesia (TGA) is a clinical syndrome of unknown etiology characterized by sudden onset anterograde amnesia, which was thought to resolve completely. However, some authors have also suggested permanent memory impairment. It is unclear whether these results reflect a true persistent damage or a simply too short assessment interval in the context of a prolonged recovery phase after TGA. To evaluate the cognitive long-term outcome, 16 patients who had suffered from TGA at a mean of 3 years before and 15 healthy controls underwent a comprehensive neuropsychological test battery. No significant differences between patients' and controls' cognitive performance were found, irrespectively of the analyzed neuropsychological domain. Therefore we hypothesize that TGA usually does not cause persistent cognitive deficits due to a generally transient and prognostic benign character.
Szczodry, Olga; van der Staay, Franz Josef; Arndt, Saskia S
To enable the development of effective treatments for dementias such as Alzheimer's disease (AD), it is important to establish valid animal models of cognitive impairments. Scopolamine is widely used to induce cognitive deficits in animal models of AD, but also causes non-cognitive side effects. We assessed whether biperiden, a selective antagonist of M1 muscarinic receptors, which are predominantly expressed in brain areas involved in cognitive processes, causes cognitive deficits without inducing peripheral side-effects. Two different doses of biperiden (3 or 10mgkg(-1)) on the acquisition of a spatial cone field task were assessed in male Lister Hooded rats. This task measures, among others, spatial working (WM) - and reference memory (RM) simultaneously. Biperiden did not impair learning of the task. The animals reached asymptotic levels for all variables except reference memory and the number of rewards collected. However, the 10mgkg(-1) dose decreased the tendency of rats to use searching strategies to solve the task and made them slower to start searching and completing the task. In conclusion, though no effects on WM and RM performance were seen, the present study cannot conclude that biperiden acts as a more selective cognition impairer than scopolamine in other rats strains and/or other doses than those tested.
Klados, Manousos A; Styliadis, Charis; Frantzidis, Christos A; Paraskevopoulos, Evangelos; Bamidis, Panagiotis D
Physical and cognitive idleness constitute significant risk factors for the clinical manifestation of age-related neurodegenerative diseases. In contrast, a physically and cognitively active lifestyle may restructure age-declined neuronal networks enhancing neuroplasticity. The present study, investigated the changes of brain's functional network in a group of elderly individuals at risk for dementia that were induced by a combined cognitive and physical intervention scheme. Fifty seniors meeting Petersen's criteria of Mild Cognitive Impairment were equally divided into an experimental (LLM), and an active control (AC) group. Resting state electroencephalogram (EEG) was measured before and after the intervention. Functional networks were estimated by computing the magnitude square coherence between the time series of all available cortical sources as computed by standardized low resolution brain electromagnetic tomography (sLORETA). A statistical model was used to form groups' characteristic weighted graphs. The introduced modulation was assessed by networks' density and nodes' strength. Results focused on the beta band (12-30 Hz) in which the difference of the two networks' density is maximum, indicating that the structure of the LLM cortical network changes significantly due to the intervention, in contrast to the network of AC. The node strength of LLM participants in the beta band presents a higher number of bilateral connections in the occipital, parietal, temporal and prefrontal regions after the intervention. Our results show that the combined training scheme reorganizes the beta-band functional connectivity of MCI patients. ClinicalTrials.gov Identifier: NCT02313935 https://clinicaltrials.gov/ct2/show/NCT02313935.
Klados, Manousos A.; Styliadis, Charis; Frantzidis, Christos A.; Paraskevopoulos, Evangelos; Bamidis, Panagiotis D.
Physical and cognitive idleness constitute significant risk factors for the clinical manifestation of age-related neurodegenerative diseases. In contrast, a physically and cognitively active lifestyle may restructure age-declined neuronal networks enhancing neuroplasticity. The present study, investigated the changes of brain's functional network in a group of elderly individuals at risk for dementia that were induced by a combined cognitive and physical intervention scheme. Fifty seniors meeting Petersen's criteria of Mild Cognitive Impairment were equally divided into an experimental (LLM), and an active control (AC) group. Resting state electroencephalogram (EEG) was measured before and after the intervention. Functional networks were estimated by computing the magnitude square coherence between the time series of all available cortical sources as computed by standardized low resolution brain electromagnetic tomography (sLORETA). A statistical model was used to form groups' characteristic weighted graphs. The introduced modulation was assessed by networks' density and nodes' strength. Results focused on the beta band (12–30 Hz) in which the difference of the two networks' density is maximum, indicating that the structure of the LLM cortical network changes significantly due to the intervention, in contrast to the network of AC. The node strength of LLM participants in the beta band presents a higher number of bilateral connections in the occipital, parietal, temporal and prefrontal regions after the intervention. Our results show that the combined training scheme reorganizes the beta-band functional connectivity of MCI patients. ClinicalTrials.gov Identifier: NCT02313935 https://clinicaltrials.gov/ct2/show/NCT02313935. PMID:26973445
Wang, S J; Furusho, M; D'Sa, C; Kuwada, S; Conti, L; Morest, D K; Bansal, R
Hearing loss has been attributed to many factors, including degeneration of sensory neurons in the auditory pathway and demyelination along the cochlear nerve. Fibroblast growth factors (FGFs), which signal through four receptors (Fgfrs), are produced by auditory neurons and play a key role in embryonic development of the cochlea and in neuroprotection against sound-induced injury. However, the role of FGF signaling in the maintenance of normal auditory function in adult and aging mice remains to be elucidated. Furthermore, the contribution of glial cells, which myelinate the cochlear nerves, is poorly understood. To address these questions, we generated transgenic mice in which Fgfr1 and Fgfr2 were specifically inactivated in Schwann cells and oligodendrocytes but not in neurons. Adult mutant mice exhibited late onset of hearing impairment, which progressed markedly with age. The hearing impairment was accompanied by significant loss of myelinated spiral ganglion neurons. The pathology extended into the cochlear nucleus, without apparent loss of myelin or of the deletion-bearing glial cells themselves. This suggests that perturbation of FGF receptor-mediated glial function leads to the attenuation of glial support of neurons, leading to their loss and impairment of auditory functions. Thus, FGF/FGF receptor signaling provides a potentially novel mechanism of maintaining reciprocal interactions between neurons and glia in adult and aging animals. Dysfunction of glial cells and FGF receptor signaling may therefore be implicated in neurodegenerative hearing loss associated with normal aging.
Ohi, Kazutaka; Hashimoto, Ryota; Ikeda, Masashi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Umeda-Yano, Satomi; Fukunaga, Masaki; Fujino, Haruo; Watanabe, Yoshiyuki; Iwase, Masao; Kazui, Hiroaki; Iwata, Nakao; Weinberger, Daniel R.; Takeda, Masatoshi
Cognitive impairments are a core feature in patients with schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Here, genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 411 healthy subjects. We attempted to replicate the GWAS data using 257 patients with schizophrenia and performed a meta-analysis of the GWAS findings and the replicated results. Because gene networks, rather than a single gene or genetic variant, may be strongly associated with the susceptibility to schizophrenia and cognitive impairments, gene-network analysis for genes in close proximity to the replicated variants was performed. We observed nominal associations between 3054 variants and cognitive phenotypes at a threshold of P < 1.0 × 10− 4. Of the 3054 variants, the associations of 191 variants were replicated in the replication samples (P < .05). However, no variants achieved genome-wide significance in a meta-analysis (P > 5.0 × 10− 8). Additionally, 115 of 191 replicated single nucleotide polymorphisms (SNPs) have genes located within 10 kb of the SNPs (60.2%). These variants were moderately associated with cognitive phenotypes that ranged from P = 2.50 × 10− 5 to P = 9.40 × 10− 8. The genes located within 10 kb from the replicated SNPs were significantly grouped in terms of glutamate receptor activity (false discovery rate (FDR) q = 4.49 × 10− 17) and the immune system related to major histocompatibility complex class I (FDR q = 8.76 × 10− 11) networks. Our findings demonstrate that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-methyl-d-aspartate glutamate network. PMID:25537281
Freitas, Sandra; Simões, Mário Rodrigues; Alves, Lara; Santana, Isabel
The Montreal Cognitive Assessment (MoCA) was recently proposed as a cognitive screening test for milder forms of cognitive impairment, having surpassed the well-known limitations of the Mini-Mental State Examination (MMSE). This study aims to validate the MoCA for screening Mild Cognitive Impairment (MCI) and Alzheimer disease (AD) through an analysis of diagnostic accuracy and the proposal of cut-offs. Patients were classified into 2 clinical groups according to standard criteria: MCI (n=90) and AD (n=90). The 2 control groups (C-MCI: n=90; C-AD: n=90) consisted of cognitively healthy community dwellers selected to match patients in sex, age, and education. The MoCA showed consistently superior psychometric properties compared with the MMSE, and higher diagnostic accuracy to discriminate between MCI (area under the curve=0.856; 95% confidence interval, 0.796-0.904) and AD patients (area under the curve=0.980; 95% confidence interval, 0.947-0.995). At an optimal cut-off of below 22 for MCI and below 17 for AD, the MoCA achieved significantly superior values in comparison with MMSE for sensitivity, specificity, positive predictive value, negative predictive value, and classification accuracy. Furthermore, the MoCA revealed higher sensitivity to cognitive decline in longitudinal monitoring. This study provides robust evidence that the MoCA is a better cognitive tool than the widely used MMSE for the screening and monitoring of MCI and AD in clinical settings.
Wollenweber, Frank Arne; Buerger, Katharina; Mueller, Claudia; Ertl-Wagner, Birgit; Malik, Rainer; Dichgans, Martin; Linn, Jennifer; Opherk, Christian
Cortical superficial siderosis (cSS) is a magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. cSS has further been identified as a risk marker for future intracranial hemorrhage. Although uncommon in the general population, cSS may be much more prevalent in high risk populations for amyloid pathology. We aimed to determine the frequency of cSS in patients with cognitive impairment presenting to a memory clinic. We prospectively evaluated consecutive patients presenting to our memory clinic between April 2011 and April 2013. Subjects received neuropsychological testing using the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD-NP). Two hundred and twelve patients with documented cognitive impairment further underwent a standardized 3T-MR-imaging protocol with T2*-weighted gradient-echo sequences for detection of cSS. Thirteen of 212 patients (6.1 %) displayed cSS. In seven of them (54 %) cSS was the only imaging sign of CAA. Patients with cSS did not differ from patients without cSS with regard to medical history, age or cardiovascular risk profile. Subjects with cSS performed worse in the mini-mental state examination (p = 0.001), showed more white matter hyperintensities (p = 0.005) and more often had microbleeds (p = 0.001) compared to those without cSS. cSS is common in patients with cognitive impairment. It is associated with lower cognitive scores, white matter hyperintensities and microbleeds and can be the only imaging sign for CAA in this patient group.
Muris, Peter; Mayer, Birgit; Freher, Nancy Kramer; Duncan, Sylvana; van den Hout, Annemiek
The present study examined age-related patterns in children's anxiety-related interpretations and internal attributions of physical symptoms. A large sample of 388 children aged between 4 and 13 years completed a vignette paradigm during which they had to explain the emotional response of the main character who experienced anxiety-related physical…
Morris, Ken A.; Gold, Paul E.
This experiment examined whether age-related changes in CREB and pCREB contribute to the rapid forgetting seen in aged animals. Young (3-month-old) and aged (24-month-old) Fischer-344 rats received inhibitory avoidance training with a low (0.2 mA, 0.4 sec) or moderate (0.5 mA, 0.5 sec) footshock; memory was measured 7 days later. Other rats were euthanized 30 minutes after training, and CREB and pCREB expression levels were examined in the hippocampus, amygdala, and piriform cortex using immunohistochemistry. CREB levels decreased with age in the hippocampus and amygdala. After training with either shock level, young rats exhibited good memory and increases in pCREB levels in the hippocampus and amygdala. Aged rats exhibited good memory for the moderate but not the low shock but did not show increases in pCREB levels after either shock intensity. These results suggest that decreases in total CREB and in pCREB activation in the hippocampus and amygdala may contribute to rapid forgetting in aged rats. After moderate footshock, the stable memory in old rats together with absence of CREB activation suggests either that CREB was phosphorylated in a spatiotemporal pattern other than analyzed here or that the stronger training conditions engaged alternate mechanisms that promote long-lasting memory. PMID:22445851
Cleutjens, Fiona AHM; Franssen, Frits ME; Spruit, Martijn A; Vanfleteren, Lowie EGW; Gijsen, Candy; Dijkstra, Jeanette B; Ponds, Rudolf WHM; Wouters, Emiel FM; Janssen, Daisy JA
Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P<0.001), planning (17.8% vs 1.1%; P<0.001), and cognitive flexibility (43.3% vs 12.2%; P<0.001). General cognitive impairment and impairments in the domains psychomotor speed, planning, and cognitive flexibility affect the COPD patients more than their matched controls. PMID:28031706
Lin, Daowei; Cao, Lin; Wang, Zhi; Li, Jiejie; Washington, Jacqueline M; Zuo, Zhiyi
Post-operative cognitive dysfunction (POCD) is a clinical phenomenon that has drawn significant attention from the public and scientific community. Age is a risk factor for POCD. However, the contribution of general anesthesia/anesthetics to POCD and the underlying neuropathology are not clear. Here, we showed that 18-month-old male Fisher 344 rats exposed to 1.2% isoflurane, a general anesthetic, for 2h had significant learning and memory impairments assessed at 2-4 weeks after isoflurane exposure. These isoflurane effects were attenuated by intravenous lidocaine (1.5mg/kg as a bolus and then 2mg/kg/h during isoflurane exposure), a local anesthetic that has neuroprotective effect. Exposure to isoflurane or isoflurane plus lidocaine did not change the neuronal and synaptic density as well as the expression of NeuN (a neuronal protein), drebrin (a dendritic spine protein), synaptophysin (a synaptic protein), activated caspase 3 and caspase-activated DNase in the hippocampus at 29 days after isoflurane exposure when cognitive impairment was present. Isoflurane and lidocaine did not affect the amount of β-amyloid peptide, total tau and phospho-tau in the cerebral cortex as well as interleukin-1β and tumor necrosis factor-α in the hippocampus at 29 days after isoflurane exposure. Thus, isoflurane induces learning and memory impairment in old rats. Lidocaine attenuates these isoflurane effects. Isoflurane may not cause long-lasting neuropathological changes.
Heckman, George A; Patterson, Christopher J; Demers, Catherine; St.Onge, Joye; Turpie, Irene D; McKelvie, Robert S
As populations age, heart failure (HF) is becoming increasingly common, and in addition to a high burden of morbidity and mortality, HF has an enormous financial impact. Though disproportionately affected by HF, the elderly are less likely to receive recommended therapies, in part because clinical trials of HF therapy have ignored outcomes of importance to this population, including impaired cognitive function (ICF). HF is associated with ICF, manifested primarily as delirium in hospitalized patients, or as mild cognitive impairment or dementia in otherwise stable outpatients. This association is likely the result of shared risk factors, as well as perfusion and rheological abnormalities that occur in patients with HF. Evidence suggests that these abnormalities may be partially reversible with standard HF therapy. The clinical consequences of ICF in HF patients are significant. Clinicians should consider becoming familiar with screening instruments for ICF, including delirium and dementia, in order to identify patients at risk of nonadherence to HF therapy and related adverse consequences. Preliminary evidence suggests that optimal HF therapy in elderly patients may preserve or even improve cognitive function, though the impact on related outcomes remains to be determined. PMID:18044137
Garcia-Ptacek, Sara; Cavallin, Lena; Kåreholt, Ingemar; Kramberger, Milica Gregoric; Winblad, Bengt; Jelic, Vesna; Eriksdotter, Maria
Background The clinical challenge in subjective cognitive impairment (SCI) is to identify which individuals will present cognitive decline. We created a statistical model to determine which variables contribute to SCI and mild cognitive impairment (MCI) versus Alzheimer's disease (AD) diagnoses. Methods A total of 993 subjects diagnosed at a memory clinic (2007-2009) were included retrospectively: 433 with SCI, 373 with MCI and 187 with AD. Descriptive statistics were provided. A logistic regression model analyzed the likelihood of SCI and MCI patients being diagnosed with AD, using age, gender, Mini-Mental State Examination score, the ratio of β-amyloid 42 divided by total tau, and phosphorylated tau as independent variables. Results The SCI subjects were younger (57.8 ± 8 years) than the MCI (64.2 ± 10.6 years) and AD subjects (70.1 ± 9.7 years). They were more educated, had less medial temporal lobe atrophy (MTA) and frequently normal cerebrospinal fluid biomarkers. Apolipoprotein E4/E4 homozygotes and apolipoprotein E3/E4 heterozygotes were significantly less frequent in the SCI group (6 and 36%) than in the AD group (28 and 51%). Within the regression model, cardiovascular risk factors, confluent white matter lesions, MTA and central atrophy increased the AD likelihood for SCI subjects. Conclusions SCI patients form a distinct group. In our model, factors suggesting cardiovascular risk, MTA and central atrophy increased the AD likelihood for SCI subjects. PMID:25538726
Halliday, Glenda M.; Leverenz, James B.; Schneider, Jay S.; Adler, Charles H.
The recent formalization of clinical criteria for PD with dementia (PD-D) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PD-D occurs on the background of severe dopamine deficits with the main pathological drivers of cognitive decline being a synergistic effect between α -synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PD-D, while others, such as parkin mutations, are associated with a reduced risk of PD-D. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. While dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies and genetic factors in PD-MCI remain to be fully elucidated. PMID:24757112
Gualtieri, C Thomas; Johnson, Lynda G
The narrow concept of mild cognitive impairment (MCI) as an early form of Alzheimer s disease has been broadened by research that established the existence of alternative forms of the condition that may presage other forms of dementia. The research presented here was a naturalistic, cross-sectional study of patients in a community referral clinic-patients with MCI and mild dementia-compared to normal controls. A comprehensive, computerized neurocognitive screening battery developed by one of the authors (CNS Vital Signs) was administered to all of the subjects. Participants consisted of 36 patients with MCI and 53 patients with mild dementia, diagnosed by standard criteria, and 89 matched normal controls. Multivariate analysis indicated significant differences among the three groups for all 15 primary test variables and for all five of the domain scores. Tests of memory, processing speed, and cognitive flexibility were the most cogent discriminators between normal controls and MCI patients, and between MCI patients and patients with mild dementia. The same three tests also had the greatest sensitivity and specificity. The results of this study indicate that computerized testing can differentiate among normal controls, MCI patients, and patients with mild dementia. Also, in a diverse group of MCI and mild dementia patients, impairments in memory, processing speed, and cognitive flexibility were the most prominent observed deficits.
Miller-Rhodes, Patrick; Popescu, Maria; Goeke, Calla; Tirabassi, Toni; Johnson, Lauren; Markowski, Vincent P
Hexabromocyclododecane (HBCD) is a brominated flame retardant that is widely-used in foam building materials and to a lesser extent, furniture and electronic equipment. After decades of use, HBCD and its metabolites have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Emerging evidence suggests that HBCD can affect early brain development and produce behavioral consequences for exposed organisms. The current study examined some of the developmental and lifelong neurobehavioral effects of prenatal HBCD exposure in a rat model. Pregnant rats were gavaged with 0, 3, 10, or 30mg/kg HBCD from gestation day 1 to parturition. A functional observation battery was used to assess sensorimotor behaviors in neonates. Locomotor and operant responding under random ratio and Go/no-go schedules of food reinforcement were examined in cohorts of young adult and aged rats. HBCD exposure was associated with increased reactivity to a tailpinch in neonates, decreased forelimb grip strength in juveniles, and impaired sustained attention indicated by Go/no-go responding in aged rats. In addition, HBCD exposure was associated with a significant increase in morbidity in the aged cohort. One health complication, a progressive loss of hindleg function, was observed only in the aged, 3mg/kg HBCD animals. These effects suggest that HBCD is a developmental neurotoxicant that can produce long-term behavioral impairments that emerge at different points in the lifespan following prenatal exposure.
Berlot, Rok; Metzler-Baddeley, Claudia; Ikram, M. Arfan; Jones, Derek K.; O’Sullivan, Michael J.
Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localized white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI). Materials and Methods: Twenty-five patients with MCI and 20 age, sex, and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI). Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusion: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for
Broster, Lucas S.; Li, Juan; Smith, Charles D.; Jicha, Gregory A.; Schmitt, Frederick A.; Jiang, Yang
Study of repeated learning mechanisms has been limited in amnestic mild cognitive impairment, a preclinical stage of Alzheimer disease modifiable by cognitive rehabilitation. We assessed repeated contextual working memory decline as an indicator of amnestic mild cognitive impairment in a sample of 45 older adults recruited from the tertiary care setting. Results indicated that contextual working memory impairment distinguished adults with preclinical disease from those without impairment despite similar overall cognitive performance, and comparison of the indicator with standard-of-care neuropsychological measures indicated discriminant validity. Contextual working memory impairment may represent a novel predictor of Alzheimer disease conversion risk. PMID:24074205
Oh, M. Matthew; Oliveira, Fernando A.; Disterhoft, John F.
A goal of many laboratories that study aging is to find a key cellular change(s) that can be manipulated and restored to a young-like state, and thus, reverse the age-related cognitive deficits. We have chosen to focus our efforts on the alteration of intrinsic excitability (as reflected by the postburst afterhyperpolarization, AHP) during the learning process in hippocampal pyramidal neurons. We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task. In the context of aging, the baseline intrinsic excitability of hippocampal neurons is decreased and therefore cognitive learning is impaired. In aging animals that are able to learn, neuron changes in excitability similar to those seen in young neurons during learning occur. Our challenge, then, is to understand how and why excitability changes occur in neurons from aging brains and cause age-associated learning impairments. After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young. Such a reversal should rescue the age-related cognitive deficits. PMID:20552042
Aggarwal, N; Wilson, R; Beck, T; Bienias, J; Bennett, D
Background: Little is known about factors that predict transition from mild cognitive impairment to Alzheimer's disease (AD). Objective: To examine the relation of impairment in different cognitive systems to risk of developing AD in persons with mild cognitive impairment. Methods: Participants are 218 older Catholic clergy members from the Religious Orders Study. At baseline, they met criteria for mild cognitive impairment based on a uniform clinical evaluation that included detailed cognitive testing. Evaluations were repeated annually for up to 10 years. Analyses were controlled for age, sex, and education. Results: Eighty two persons (37.6%) developed AD. In separate analyses, episodic memory, semantic memory, working memory, and perceptual speed, but not visuospatial ability, were associated with risk of AD, but when analysed together only episodic memory and perceptual speed were associated with AD incidence, with the effect for episodic memory especially strong. Overall, those with impaired episodic memory were more than twice as likely to develop AD as those with impairment in other cognitive domains (relative risk (RR) = 2.45; 95% confidence interval (CI): 1.53 to 3.92), and they experienced more rapid cognitive decline. Lower episodic memory performance was associated with increased risk of AD throughout the observation period, whereas impairment in other cognitive domains was primarily associated with risk during the following year but not thereafter. Conclusion: Among persons with mild cognitive impairment, episodic memory impairment is associated with a substantial and persistent elevation in risk of developing AD compared to impairment in other cognitive systems. PMID:16227534
Belleville, Sylvie; Ménard, Marie-Claude; Lepage, Emilie
The goal of this study was to assess the effect of novelty on correct recognition (hit minus false alarms) and on recollection and familiarity processes in normal aging and amnestic mild cognitive impairment (MCI). Recognition tasks compared well-known and novel stimuli in the verbal domain (words vs. pseudowords) and in the musical domain (well-known vs. novel melodies). Results indicated that novel materials associated with lower correct recognition and lower recollection, an effect that can be related to its lower amenability to elaborative encoding in comparison with well-known items. Results also indicated that normal aging impairs recognition of well-known items, whereas MCI impairs recognition of novel items only. Healthy older adults showed impaired recollection and familiarity relative to younger controls and individuals with MCI showed impaired recollection relative to healthy older adults. The recollection deficit in healthy older adults and persons with MCI and their impaired recognition of well-known items is compatible with the difficulty both groups have in encoding information in an elaborate manner. In turn, familiarity deficit could be related to impaired frontal functioning. Therefore, novelty of material has a differential impact on recognition in persons with age-related memory disorders.
Meakin, Lee B; Galea, Gabriel L; Sugiyama, Toshihiro; Lanyon, Lance E; Price, Joanna S
Bones adjust their mass and architecture to be sufficiently robust to withstand functional loading by adapting to their strain environment. This mechanism appears less effective with age, resulting in low bone mass. In male and female young adult (17-week-old) and old (19-month-old) mice, we investigated the effect of age in vivo on bones' adaptive response to loading and in vitro in primary cultures of osteoblast-like cells derived from bone cortices. Right tibias were axially loaded on alternate days for 2 weeks. Left tibias were non-loaded controls. In a separate group, the number of sclerostin-positive osteocytes and the number of periosteal osteoblasts were analyzed 24 hours after a single loading episode. The responses to strain of the primary osteoblast-like cells derived from these mice were assessed by EGR2 expression, change in cell number and Ki67 immunofluorescence. In young male and female mice, loading increased trabecular thickness and the number of trabecular connections. Increase in the number of trabecular connections was impaired with age but trabecular thickness was not. In old mice, the loading-related increase in periosteal apposition of the cortex was less than in young ones. Age was associated with a lesser loading-related increase in osteoblast number on the periosteal surface but had no effect on loading-related reduction in the number of sclerostin-positive osteocytes. In vitro, strain-related proliferation of osteoblast-like cells was lower in cells from old than young mice. Cells from aged female mice demonstrated normal entry into the cell cycle but subsequently arrested in G2 phase, reducing strain-related increases in cell number. Thus, in both male and female mice, loading-related adaptive responses are impaired with age. This impairment is different in females and males. The deficit appears to occur in osteoblasts' proliferative responses to strain rather than earlier strain-related responses in the osteocytes. © 2014 The Authors
reflexes provide a simple and robust method to study vision in passive/immature/ impaired observers. For example, oculomotor reflexes are widely used to...dysfunctions in cognitively impaired observers PRINCIPAL INVESTIGATOR: YuryPetrov,Ph.D...September 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Oculomotor reflexes as a test of visual dysfunctions in cognitively impaired observers 5b
Occupational noise, smoking, and a high body mass index are risk factors for age-related hearing impairment and moderate alcohol consumption is protective: a European population-based multicenter study.
Fransen, Erik; Topsakal, Vedat; Hendrickx, Jan-Jaap; Van Laer, Lut; Huyghe, Jeroen R; Van Eyken, Els; Lemkens, Nele; Hannula, Samuli; Mäki-Torkko, Elina; Jensen, Mona; Demeester, Kelly; Tropitzsch, Anke; Bonaconsa, Amanda; Mazzoli, Manuela; Espeso, Angeles; Verbruggen, Katia; Huyghe, Joke; Huygen, Patrick L M; Kunst, Sylvia; Manninen, Minna; Diaz-Lacava, Amalia; Steffens, Michael; Wienker, Thomas F; Pyykkö, Ilmari; Cremers, Cor W R J; Kremer, Hannie; Dhooge, Ingeborg; Stephens, Dafydd; Orzan, Eva; Pfister, Markus; Bille, Michael; Parving, Agnete; Sorri, Martti; Van de Heyning, Paul; Van Camp, Guy
A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.
Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study
Fransen, Erik; Topsakal, Vedat; Hendrickx, Jan-Jaap; Van Laer, Lut; Huyghe, Jeroen R.; Van Eyken, Els; Lemkens, Nele; Hannula, Samuli; Mäki-Torkko, Elina; Jensen, Mona; Demeester, Kelly; Tropitzsch, Anke; Bonaconsa, Amanda; Mazzoli, Manuela; Espeso, Angeles; Verbruggen, Katia; Huyghe, Joke; Huygen, Patrick L. M.; Kunst, Sylvia; Manninen, Minna; Diaz-Lacava, Amalia; Steffens, Michael; Wienker, Thomas F.; Pyykkö, Ilmari; Cremers, Cor W. R. J.; Kremer, Hannie; Dhooge, Ingeborg; Stephens, Dafydd; Orzan, Eva; Pfister, Markus; Bille, Michael; Parving, Agnete; Sorri, Martti; Van de Heyning, Paul
A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment. Electronic supplementary material The online version of this article (doi: 10.1007/s10162-008-0123-1) contains supplementary material, which is available to authorized users. PMID:18543032
Koh, Ming Teng; Rosenzweig-Lipson, Sharon; Gallagher, Michela
A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer’s disease. Compounds that act as positive allosteric modulators at GABAA α5 receptors might be useful in targeting this condition because GABAA α5 receptors mediate tonic inhibition of principal neurons in the affected network. While agents to improve cognitive function in the past focused on inverse agonists, which are negative allosteric modulators at GABAA α5 receptors, research supporting that approach used only young animals and predated current evidence for excessive hippocampal activity in age-related conditions of cognitive impairment. Here, we used two compounds, Compound 44 [6,6-dimethyl-3-(3-hydroxypropyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one] and Compound 6 [methyl 3,5-diphenylpyridazine-4-carboxylate], with functional activity as potentiators of γ-aminobutyric acid at GABAA α5 receptors, to test their ability to improve hippocampal-dependent memory in aged rats with identified cognitive impairment. Improvement was obtained in aged rats across protocols differing in motivational and performance demands and across varying retention intervals. Significant memory improvement occurred after either intracereboventricular infusion with Compound 44 (100 μg) in a water maze task or systemic administration with Compound 6 (3 mg/kg) in a radial arm maze task. Furthermore, systemic administration improved behavioral performance at dosing shown to provide drug exposure in the brain and in vivo receptor occupancy in the hippocampus. These data suggest a novel approach to improve neural network function in clinical conditions of excess hippocampal activity. PMID:22732440
Tang, Feng Ru; Loke, Weng Keong; Khoo, Boo Cheong
Irradiation of the brain in early human life may set abnormal developmental events into motion that last a lifetime, leading to a poor quality of life for affected individuals. While the effect of irradiation at different early developmental stages on the late human life has not been investigated systematically, animal experimental studies suggest that acute postnatal irradiation with ⩾0.1Gy may significantly reduce neurogenesis in the dentate gyrus and endotheliogenesis in cerebral vessels and induce cognitive impairment and aging. Fractionated irradiation also reduces neurogenesis. Furthermore, irradiation induces hippocampal neuronal loss in CA1 and CA3 areas, neuroinflammation and reduces gliogenesis. The hippocampal neurovascular niche and the total number of microvessels are also changed after radiation exposures. Each or combination of these pathological changes may cause cognitive impairment and aging. Interestingly, acute irradiation of aged brain with a certain amount of radiation has also been reported to induce brain hormesis or neurogenesis. At molecular levels, inflammatory cytokines, chemokines, neural growth factors, neurotransmitters, their receptors and signal transduction systems, reactive oxygen species are involved in radiation-induced adverse effect on brain development and functions. Further study at different omics levels after low dose/dose rate irradiation may not only unravel the mechanisms of radiation-induced adverse brain effect or hormesis, but also provide clues for detection or diagnosis of radiation exposure and for therapeutic approaches to effectively prevent radiation-induced cognitive impairment and aging. Investigation focusing on radiation-induced changes of critical brain development events may reveal many previously unknown adverse effects.
Peraita, Herminia; Chacón, José; Díaz-Mardomingo, Carmen; Martínez-Arias, Rosario
We applied latent class analysis (LCA) to a set of neuropsychological data with the aim of corroborating the three cognitive profiles of mild cognitive impairment (MCI) described in the literature, namely: healthy, amnestic, non-amnestic, and multidomain. The ultimate purpose of the LCA was to try to find the underlying classification of MCI and related pathologies by means of the participants' response patterns, rather than on more classical psychometric criteria, such as the standard deviation of the mean. We computed 547 neuropsychological assessments derived from 223 participants who were assessed annually for three consecutive years. The battery included tests of memory, language, executive function, and praxis. The results obtained by means of LCA, with a four-group solution and using the 40th percentile as the criterion, confirm prior classifications obtained with more questionable psychometric criteria, while providing longitudinal data on the course of MCI and the stability of group assignment over time.
Watkins, Crystal C; Treisman, Glenn J
The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression), minor cognitive-motor dysfunction, and HIV-associated dementia. PMID:25678819
Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène
The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates.
Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène
The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates. PMID:26834666
Eppig, Joel; Wambach, Denene; Nieves, Christine; Price, Catherine C.; Lamar, Melissa; Delano-Wood, Lisa; Giovannetti, Tania; Bettcher, Brianne M.; Penney, Dana L.; Swenson, Rod; Lippa, Carol; Kabasakalian, Anahid; Bondi, Mark W.; Libon, David J.
Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI. PMID:22014116
Popp, Julius; Schaper, Karsten; Kölsch, Heike; Cvetanovska, Gabriela; Rommel, Fatima; Klingmüller, Dietrich; Dodel, Richard; Wüllner, Ullrich; Jessen, Frank
Hypercortisolaemia occurs in Alzheimer's disease (AD) and may be involved in the AD related neurodegenerative process. In order to determine whether brain structures are exposed to high cortisol concentrations early in AD, we measured cerebrospinal fluid (CSF) cortisol in 66 subjects with AD, 33 subjects with mild cognitive impairment (MCI) and 34 control subjects. CSF cortisol concentrations were higher in AD subjects compared to controls (p<0.001) and to MCI subjects (p=0.002). There was no significant increase of cortisol in MCI subjects compared with controls suggesting that the increase of CSF cortisol is not an early event in the course of AD.
Cooper, Claudia; Li, Ryan; Lyketsos, Constantine; Livingston, Gill
Background More people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia but we do not know how to reduce deterioration. Aims To systematically review Randomised Controlled Trials (RCTs) evaluating effects of any intervention for MCI on cognitive, neuropsychiatric, functional, global outcomes, life quality, or incident dementia. Methods We reviewed the 41 studies fitting predetermined criteria, assessed validity using a checklist, calculated standardised outcomes, and prioritised primary outcome findings in placebo-controlled studies. Results The strongest evidence was that cholinesterase inhibitors did not reduce incident dementia. Cognition improved in single trials of: a heterogeneous psychological group intervention over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48 weeks. Nicotine improved attention over 6 months. There was equivocal evidence that Huannao Yicong improved cognition and social functioning. Conclusions There was no replicated evidence that any intervention was effective. Cholinesterase inhibitors and rofecoxib are ineffective in preventing dementia. Further good quality RCTs are necessary and preliminary evidence suggests these should include trials of psychological group interventions and piribedil. PMID:24085737
Diciotti, Stefano; Ciulli, Stefano; Ginestroni, Andrea; Salvadori, Emilia; Poggesi, Anna; Pantoni, Leonardo; Inzitari, Domenico; Mascalchi, Mario; Toschi, Nicola
Vascular mild cognitive impairment (VMCI) is a disorder in which multimodal MRI can add significant value by combining diffusion tensor imaging (DTI) with brain morphometry. In this study we implemented and compared machine learning techniques for multimodal classification between 58 VMCI patients and 29 healthy subjects as well as for discrimination (within the VMCI group) between patients with different cognitive performances. For each subject, a cortical feature vector was constructed based on cortical parcellation and cortical and subcortical volumetric segmentation and a DTI feature vector was formed by combining descriptive statistical metrics related to the distribution of DTI invariants within white matter. We employed both a sequential minimal optimization and a functional tree classifier, using feature selection and 10-fold cross-validation, and compared their performances in monomodal and multimodal classification for both classification problems (healthy subjects vs VMCI and prediction of cognitive performance). While monomodal classification resulted in satisfactory performance in most cases, turning from monomodal to multimodal classification resulted in an improvement of the performance in the discrimination between VMCI patients with low cognitive performance and healthy subjects by up to 10% in sensitivity (leaving specificity unchanged). We therefore are able to confirm the usefulness of machine learning techniques in discriminating diseased states based on neuroimaging data.
Kim, Jong Hun; Lee, Jong Weon; Kim, Geon Ha; Roh, Jee Hoon; Kim, Min-Jeong; Seo, Sang Won; Kim, Sung Tae; Jeon, Seun; Lee, Jong-Min; Heilman, Kenneth M; Na, Duk L
There are functional and structural neocortical hemispheric asymmetries in people with normal cognition. These asymmetries may be altered in patients with Alzheimer's disease (AD) because there is a loss of neuronal connectivity in the heteromodal cortex. The purpose of this study is to test the hypothesis that individuals with amnestic mild cognitive impairment (aMCI), mild AD, and moderate to severe AD have progressive reductions in thickness asymmetries of the heteromodal neocortex. Right-handed elderly volunteers including normal cognition (NC), aMCI, and AD underwent 3-D volume imaging for cortical thickness. Although the cortical asymmetry pattern observed in normal cognition brains was generally maintained in aMCI and AD, there was a progressive decrease in the degree of asymmetry, especially in the inferior parietal lobule. A reduction of neocortical asymmetries may be a characteristic sign that occurs in patients with AD. Future studies are needed to evaluate whether this loss is specific to AD and if measurements of asymmetry can be used as diagnostic markers and for monitoring disease progression.
Cardinali, Daniel P; Vigo, Daniel E; Olivar, Natividad; Vidal, María F; Furio, Analía M; Brusco, Luis I
Mild cognitive impairment (MCI) is an etiologically heterogeneous syndrome defined by cognitive impairment in advance of dementia. We previously reported in a retrospective analysis that daily 3 - 9 mg of a fast-release melatonin preparation given p. o. at bedtime for up to 3 years significantly improved cognitive and emotional performance and daily sleep/wake cycle in MCI patients. In a follow up of that study we now report data from another series of 96 MCI outpatients, 61 of who had received daily 3 - 24 mg of a fast-release melatonin preparation p. o. at bedtime for 15 to 60 months. Melatonin was given in addition to the standard medication prescribed by the attending psychiatrist. Patients treated with melatonin exhibited significantly better performance in Mini–Mental State Examination and the cognitive subscale of the Alzheimer’s disease Assessment Scale. After application of a neuropsychological battery comprising a Mattis´ test, Digit-symbol test, Trail A and B tasks and the Rey´s verbal test, better performance was found in melatonin-treated patients for every parameter tested. Abnormally high Beck Depression Inventory scores decreased in melatonin-treated patients, concomitantly with the improvement in the quality of sleep and wakefulness. The comparison of the medication profile in both groups of MCI patients indicated that 9.8% in the melatonin group received benzodiazepines vs. 62.8% in the non-melatonin group. The results further support that melatonin can be a useful add-on drug for treating MCI in a clinic environment. PMID:23383398
Atkinson, Joanna; Denmark, Tanya; Marshall, Jane; Mummery, Cath; Woll, Bencie
To provide accurate diagnostic screening of deaf people who use signed communication, cognitive tests must be devised in signed languages with normative deaf samples. This article describes the development of the first screening test for the detection of cognitive impairment and dementia in deaf signers. The British Sign Language Cognitive Screening Test uses standardized video administration to screen cognition using signed, rather than spoken or written, instructions and a large norm-referenced sample of 226 deaf older people. Percentiles are provided for clinical comparison. The tests showed good reliability, content validity, and correlation with age, intellectual ability, and education. Clinical discrimination was shown between the normative sample and 14 deaf patients with dementia. This innovative testing approach transforms the ability to detect dementia in deaf people, avoids the difficulties of using an interpreter, and enables culturally and linguistically sensitive assessment of deaf signers, with international potential for adaptation into other signed languages.
Moro, V; Condoleo, M T; Valbusa, V; Broggio, E; Moretto, G; Gambina, G
Executive functions play an important role in the maintenance of autonomy in day-to-day activities. Nevertheless, there is little research into specific cognitive training for Mild Cognitive Impairment (MCI). We present the results of a program which aims to teach specific strategies and metacognitive abilities in order for patients to be able to carry out attentional and executive tasks. Two groups (A and B) were compared in a cross-over design. After the first evaluation, Group A (but not B) participated in a six month cognitive stimulation program. After a second assessment, only Group B received treatment and then a final evaluation was carried out on both groups. The results show that: i) both groups improved their performance as an effect of training; ii) improvements generalized to memory and general cognitive tasks; iii) in the interval without training, Group B's performance worsened and iv) Group A partially maintained their results over time.
Cloutier, Simon; Chertkow, Howard; Kergoat, Marie-Jeanne; Gauthier, Serge; Belleville, Sylvie
Abstract Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer’s disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults. PMID:26401770
Tamamizu-Kato, Shiori; Wong, Jason Yiu; Jairam, Vikram; Uchida, Koji; Raussens, Vincent; Kato, Hiroyuki; Ruysschaert, Jean-Marie; Narayanaswami, Vasanthy
Oxidative damage to proteins such as apolipoprotein B-100 increases the atherogenicity of low-density lipoproteins (LDL). However, little is known about the potential oxidative damage to apolipoprotein E (apoE), an exchangeable antiatherogenic apolipoprotein. ApoE plays an integral role in lipoprotein metabolism by regulating the plasma cholesterol and triglyceride levels. Hepatic uptake of lipoproteins is facilitated by apoE's ability to bind with cell surface heparan sulfate proteoglycans and to lipoprotein receptors via basic residues in its 22 kDa N-terminal domain (NT). We investigated the effect of acrolein, an aldehydic product of endogenous lipid peroxidation and a tobacco smoke component, on the conformation and function of recombinant human apoE3-NT. Acrolein caused oxidative modification of apoE3-NT as detected by Western blot with acrolein-lysine-specific antibodies, and tertiary conformational alterations. Acrolein modification impairs the ability of apoE3-NT to interact with heparin and the LDL receptor. Furthermore, acrolein-modified apoE3-NT displayed a 5-fold decrease in its ability to interact with lipid surfaces. Our data indicate that acrolein disrupts the functional integrity of apoE3, which likely interferes with its role in regulating plasma cholesterol homeostasis. These observations have implications regarding the role of apoE in the pathogenesis of smoking- and oxidative stress-mediated cardiovascular and cerebrovascular diseases.
Larner, A J
The diagnostic accuracy of the AD8 informant questionnaire for cognitive impairment was assessed in patients referred to a dedicated memory clinic. This pragmatic prospective study of consecutive referrals attending with an informant who completed AD8 (n = 212) lasted 12 months. Diagnosis used standard clinical diagnostic criteria for dementia and mild cognitive impairment as reference standard (prevalence of cognitive impairment = 0.62). The AD8 proved acceptable to informants, was quick, and easy to use. Using the cutoff of ≥2/8, AD8 was highly sensitive (0.97) for diagnosis of cognitive impairment but specificity was poor (0.17). Combining AD8 with either the Mini-Mental State Examination or the Six-Item Cognitive Impairment Test showed little additional diagnostic benefit. In conclusion, AD8 is very sensitive for cognitive impairment in a memory clinic but specificity may be inadequate.
Zhang, Zhenmei; Hayward, Mark D.; Yu, Yan-Liang
Blacks are especially hard hit by cognitive impairment at older ages compared to whites. Here, we take advantage of the Health and Retirement Study (1998–2010) to assess how this racial divide in cognitive impairment is associated with the racial stratification of life course exposures and resources over a 12-year period among 8,946 non-Hispanic whites and blacks aged 65 and older in 1998. We find that blacks suffer from a higher risk of moderate/severe cognitive impairment at baseline and during the follow-up. Blacks are also more likely to report childhood adversity and to have grown up in the segregated South, and these early-life adversities put blacks at a significantly higher risk of cognitive impairment. Adulthood socioeconomic status is strongly associated with the risk of cognitive impairment, net of childhood conditions. However, racial disparities in cognitive impairment, though substantially reduced, are not eliminated when controlling for these life course factors. PMID:27247126
Cognitive impairment associated with childhood-onset epilepsy is an important consequence in the developing brain owing to its negative effects on neurodevelopmental and social outcomes. While the cause of cognitive impairment in epilepsy appears to be multifactorial, epilepsy-related factors such as type of epilepsy and underlying etiology, age at onset, frequency of seizures, duration of epilepsy, and its treatment are considered important. In recent studies, antecedent cognitive impairment before the first recognized seizure and microstructural and functional alteration of the brain at onset of epilepsy suggest the presence of a common neurobiological mechanism between epilepsy and cognitive comorbidity. However, the overall impact of cognitive comorbidity in children with epilepsy and the independent contribution of each of these factors to cognitive impairment have not been clearly delineated. This review article focuses on the significant contributors to cognitive impairment in children with epilepsy. PMID:27186225
Zhang, Jie; Shi, Jie; Stonnington, Cynthia; Li, Qingyang; Gutman, Boris A; Chen, Kewei; Reiman, Eric M; Caselli, Richard J; Thompson, Paul M; Ye, Jieping; Wang, Yalin
Mild Cognitive Impairment (MCI) is a transitional stage between normal age-related cognitive decline and Alzheimer's disease (AD). Here we introduce a hyperbolic space sparse coding method to predict impending decline of MCI patients to dementia using surface measures of ventricular enlargement. First, we compute diffeomorphic mappings between ventricular surfaces using a canonical hyperbolic parameter space with consistent boundary conditions and surface tensor-based morphometry is computed to measure local surface deformations. Second, ring-shaped patches of TBM features are selected according to the geometric structure of the hyperbolic parameter space to initialize a dictionary. Sparse coding is then applied on the patch features to learn sparse codes and update the dictionary. Finally, we adopt max-pooling to reduce the feature dimensions and apply Adaboost to predict AD in MCI patients (N = 133) from the Alzheimer's Disease Neuroimaging Initiative baseline dataset. Our work achieved an accuracy rate of 96.7% and outperformed some other morphometry measures. The hyperbolic space sparse coding method may offer a more sensitive tool to study AD and its early symptom.
Aurtenetxe, Sara; García-Pacios, Javier; del Río, David; López, María E.; Pineda-Pardo, José A.; Marcos, Alberto; Delgado Losada, Maria L.; López-Frutos, José M.; Maestú, Fernando
Mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia, specifically Alzheimer's disease (AD). The most common cognitive impairment of MCI includes episodic memory loss and difficulties in working memory (WM). Interference can deplete WM, and an optimal WM performance requires an effective control of attentional resources between the memoranda and the incoming stimuli. Difficulties in handling interference lead to forgetting. However, the interplay between interference and WM in MCI is not well-understood and needs further investigation. The current study investigated the effect of interference during a WM task in 20 MCIs and 20 healthy elder volunteers. Participants performed a delayed match-to-sample paradigm which consisted in two interference conditions, distraction and interruption, and one control condition without any interference. Results evidenced a disproportionate impact of interference on the WM performance of MCIs, mainly in the presence of interruption. These findings demonstrate that interference, and more precisely interruption, is an important proxy for memory-related deficits in MCI. Thus, the current findings reveal novel evidence regarding the causes of WM forgetting in MCI patients, associated with difficulties in the mechanisms of attentional control. PMID:27790082
Haussmann, Robert; Werner, Annett; Gruschwitz, Antonia; Osterrath, Antje; Lange, Jan; Donix, Katharina L; Linn, Jennifer; Donix, Markus
Patients with amnestic mild cognitive impairment (aMCI) are at risk for developing Alzheimer's disease. Due to their prominent memory impairment, structural magnetic resonance imaging (MRI) often focuses on the hippocampal region. However, recent positron-emission tomography data suggest that within a network of frontal and temporal changes, patients with aMCI show metabolic alterations in the precuneus, a key region for higher cognitive functions. Using high-resolution MRI and whole-brain cortical thickness analyses in 28 patients with aMCI and 25 healthy individuals, we wanted to investigate whether structural changes in the precuneus would be associated with cortical thickness reductions in frontal and temporal brain regions in patients with aMCI. In contrast to healthy people, patients with aMCI showed an association of cortical thinning in the precuneus with predominantly left-hemispheric thickness reductions in medial temporal and frontal cortices. Our data highlight structural neuronal network characteristics among patients with aMCI.
Sakakibara, Ryuji; Ogata, Takeshi; Haruta, Masayuki; Kishi, Masahiko; Tsuyusaki, Yohei; Tateno, Akihiko; Tateno, Fuyuki; Mouri, Takayuki
Objectives: We reported cases of amnestic mild cognitive impairment (MCI) without the core clinical features of dementia with Lewy bodies (DLB) (dementia and spontaneous parkinsonism) with low uptake in 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. Methods: During a 3-year period at a university clinic, we had 254 patients with memory complaints; 106 men, 148 women; mean age 72.5 years (48-95 years). In all patients we performed neurologic examination; memory tests including the MMSE, ADAScog, FAB and additional WMS-R; and imaging tests including brain MRI, SPECT and MIBG scintigraphy. Results: The criteria of amnestic MCI were fulfilled in 44 patients; and 13 of them (30%) showed low MIBG uptake. They had the following: uniformly elderly, with an equal sex ratio, have relatively slow progression, preserved general cognitive function (MMSE 24.8/30). In addition to memory impairment, they commonly showed low frontal function by FAB (12.5/18) and some had mild visual hallucination (5). Other than memory disorder, they had autonomic disorder (nocturia in 7, constipation in 2, postural hypotension in one), REM sleep behavioral disorder (in 3) and occipital hypoperfusion by SPECT (in 5). Conclusion: This cohort of multidomain amnestic MCI cases may present with early stage DLB because of the presence of low MIBG uptake. Clinically, they commonly have low FAB, and may have visual hallucination, autonomic and sleep disorders. PMID:23383388
Kubicki, Alexandre; Fautrelle, Lilian; Bourrelier, Julien; Rouaud, Olivier; Mourey, France
Objectives: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity in muscle synergies involved in an arm-pointing movement in functionally unimpaired MCI patients. We hypothesized that early motor indicators exist in this population at a preclinical level. Methods: Electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Older Adults (OA), and MCI patients. The OA and MCI groups presented the same functional status. Each subject performed 20 arm-pointing movements from a standing position. Results: The main differences were (1) an earlier activation of the left Obliquus internus in MCI compared with OA group, (2) an earlier activation for the MCI compared with both OA and YA. The temporal differences in muscle synergies between MCI and OA groups were linked with executive functions of MCI patients, assessed by the trail making test. Moreover, the results show a delayed activation of the right Biceps Femoris and the right Erector Spinae at l3 in MCI and OA compared with YA. Interpretation: The motor program changes highlighted in our patient MCI group suggest that discrete modifications of the motor command seem to exist even in the absence of functional impairment. Instead of showing an indication of delayed muscle activation in the MCI patients, our results highlight some early activation of several trunk muscles. PMID:27570509
Sheppard, David P.; Iudicello, Jennifer E.; Bondi, Mark W.; Doyle, Katie L.; Morgan, Erin E.; Massman, Paul J.; Gilbert, Paul E.; Woods, Steven Paul
With the rising number of individuals in their 50s and 60s who are infected with HIV, concerns have emerged about possible increases in the rates of non-HIV-associated dementias. The current study examined the prevalence of mild cognitive impairment (MCI) in older HIV-infected adults, since MCI is an intermediate state between typical cognitive aging and dementia that emerges in this age range. Participants included 75 adults with HIV disease aged 50 years and older who were on cART and had undetectable plasma viral loads and 80 demographically similar HIV seronegative comparison subjects. Participants completed a research neuropsychological evaluation that was used to classify MCI according to the comprehensive diagnostic scheme described by Bondi et al. (2014). HIV-infected persons were over seven times more likely to have an MCI designation (16%) than their seronegative counterparts (2.5%). Within the HIV+ cohort, MCI had minimal overlap with diagnoses of Asymptomatic Neurocognitive Impairment and was significantly associated with older age, lower Karnofsky Scale of Performance Scores, and mild difficulties performing instrumental activities of daily living (iADLs). HIV infection in older adults is associated with a notably elevated concurrent risk of MCI, which may increase the likelihood of developing non-HIV-associated dementias as this population ages further. PMID:26139019
Aurtenetxe, Sara; García-Pacios, Javier; Del Río, David; López, María E; Pineda-Pardo, José A; Marcos, Alberto; Delgado Losada, Maria L; López-Frutos, José M; Maestú, Fernando
Mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia, specifically Alzheimer's disease (AD). The most common cognitive impairment of MCI includes episodic memory loss and difficulties in working memory (WM). Interference can deplete WM, and an optimal WM performance requires an effective control of attentional resources between the memoranda and the incoming stimuli. Difficulties in handling interference lead to forgetting. However, the interplay between interference and WM in MCI is not well-understood and needs further investigation. The current study investigated the effect of interference during a WM task in 20 MCIs and 20 healthy elder volunteers. Participants performed a delayed match-to-sample paradigm which consisted in two interference conditions, distraction and interruption, and one control condition without any interference. Results evidenced a disproportionate impact of interference on the WM performance of MCIs, mainly in the presence of interruption. These findings demonstrate that interference, and more precisely interruption, is an important proxy for memory-related deficits in MCI. Thus, the current findings reveal novel evidence regarding the causes of WM forgetting in MCI patients, associated with difficulties in the mechanisms of attentional control.
Armstrong, Carol L.; Shera, David M.; Lustig, Robert A.; Phillips, Peter C.
Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.
Callahan, Kathryn E.; Lovato, James F.; Miller, Michael E.; Easterling, Doug; Snitz, Beth; Williamson, Jeff D.
OBJECTIVES To determine whether older adults with mild cognitive impairment (MCI), a condition not previously explored as a risk factor, experience increased hospitalizations and 30-day readmission compared to those with normal cognition. Frequent hospitalizations and unplanned readmissions are recognized as markers of poor quality care for older adults. DESIGN Post-hoc analysis of prospectively gathered data on incident hospitalization and readmission from the Ginkgo Evaluation of Memory Study (GEMS), a randomized double-blind placebo-controlled trial designed to assess the impact of Ginkgo biloba on incidence of dementia. SETTING GEMS was conducted in 5 academic medical centers in the United States. PARTICIPANTS 2742 community-dwelling adults age 75 or older with normal cognition (n=2314) or MCI (n=428) at baseline cognitive testing. MEASUREMENTS Index hospitalization and 30-day hospital readmission, adjusted for age, sex, race, education, clinic site, trial assignment status, comorbidities, number of prescription medications, and living with an identified proxy. RESULTS MCI was associated with a 17% increase in the hazard of index hospitalization as compared with normal cognition (adjusted Hazard Ratio (HR)=1.17 (1.02 – 1.34)). In participants who lived with their proxy, MCI was associated with a 39% increased hazard of index hospitalization (adjusted HR=1.392 (1.169 – 1.657)). Baseline MCI was not associated with increased odds of 30-day hospital readmission (adjusted Odds Ratio=0.90 (0.60 – 1.36)). CONCLUSION MCI may represent a target condition for healthcare providers to coordinate support services in an effort to reduce hospitalization and subsequent disability. PMID:26313420
The C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene differs in frequency in different ethnic groups which have differing prevalence of age-related cognitive impairments. We used a battery of neuropsychological tests to examine association of the MTHFR C677T polymorphism w...
Ihle, Andreas; Jopp, Daniela S.; Oris, Michel; Fagot, Delphine; Kliegel, Matthias
Health research suggests that findings on young-old adults cannot be generalized to old-old adults and thus that old-old age seems not a simple continuation of young-old age due to qualitative changes that result in a discontinuity in old age. Specifically, it would be of conceptual and methodological importance to inform research regarding estimates around which chronological age the beginning of old-old age could be placed at a population level, and whether this is universal or domain-specific. To derive such criteria, we investigated potential discontinuity of age relations between young-old and old-old age in a large population-based sample considering measures in different domains (processing speed, verbal abilities, general health status, activity participation, and life satisfaction). For processing speed, verbal abilities, general health status, and life satisfaction we observed some very small indication that there might be a discontinuity of age relations at the end of individuals’ eighties, and for activity participation already at the beginning of individuals’ eighties. In conclusion, models conceptualizing aging as a gradual development might not suffice to adequately represent the differences between the stages of young-old and old-old age due to some very small indication that there might be discontinuity in late adulthood. PMID:27827960
Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul
Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.
Kandikattu, Hemanth Kumar; Deep, Satya Narayan; Razack, Sakina; Amruta, Narayanappa; Prasad, Dipti; Khanum, Farhath
Hypobaric hypoxia leads to decrease in cellular oxygen content which subsequently damages the hippocampus with an increase in brain oxidative stress and impairs the memory of the individual. In the present study, we have evaluated the cognitive impairment modulating activity of total oligomeric flavonoids fraction of Cyperus rotundus (TOF) in Sprague Dawley rats. The rats were trained for memory activity for a period of 7days followed by 7days exposure to 25,000ft. altitude and the spatial reference memory was evaluated. Behavioral analysis of the rats by Morris water maze experiment showed that TOF supplementation enhanced the spatial reference memory activity of the rats exposed to hypobaric hypoxia. The decrease in antioxidant status of the animals exposed to hypoxia was restored with TOF supplementation. The increase in ROS, lipid peroxidation products and protein carbonyls of the hippocampus was significantly decreased in animals with TOF administration. The histological assessment of the pyramidal cells of the hippocampus of hypoxia-exposed animals showed nuclear damage and TOF supplementation prevented nuclear damage. TOF administration suppressed hypoxia-induced increase in serotonin, dopamine, and norepinephrine. GABA and Ach levels were decreased by hypoxia which was prevented by TOF supplementation. The increase in GFAP, HIF-1α and VEGF expression in CA3 region of the hippocampus in hypoxia-exposed rats was decreased in TOF administered rats. Taken together, TOF extract ameliorates hypobaric hypoxia induced memory impairment and neurodegeneration in hippocampus through its anti-stress effects.
Dai, Baozhen; Mao, Zongfu; Mei, John; Levkoff, Sue; Wang, Huali; Pacheco, Misty; Wu, Bei
This study aimed to examine the experience and knowledge of mild cognitive impairment (MCI) among Chinese family caregivers of individuals with MCI. The sample was recruited from memory clinics in Zhongnan Hospital in Wuhan, China. In-depth semi-structured interviews were used. Thirteen family members of individuals diagnosed with MCI participated in the study. Data analysis revealed three themes: 1) initial recognition of cognitive decline; 2) experience of the diagnosis of MCI; 3) perception of cognitive decline as a normal part of aging. While family members recognized the serious consequences of memory loss (e.g. getting lost), they would typically not take their family members to see a doctor until something specific triggered their access to the medical care system. The Chinese traditional perception of dementia as part of normal aging may serve to lessen the stigma of individuals with MCI, while the term "laonian chidai" which literally translates to "stupid, demented elderly" may exacerbate the stigma associated with individuals with MCI. It is suggested that family members' worries may be relieved by improving their access to accurate knowledge of the disease, community-based and institutional care services, and culturally appropriately words are needed for MCI.
Dubey, Shagun; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen
Objective: To study the effect of the co-administration of phenytoin (PHT) and rutin in comparison with PHT and piracetam (PIM) on seizure control, cognitive, and motor functions in mice. Materials and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the co-administration of PHT and PIM on convulsions. Cognitive functions in mice were assessed by a spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetyl-cholinesterase (AChE) activity was also estimated. Statistical Analysis: The expression of data was done as mean ± standard error of the mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett's test. P < 0.05 was considered significant. Results: The study showed that rutin when co-administered with PHT, significantly reversed PHT-induced reduction in spontaneous alternation without altering the efficacy of PHT against ICES, in both acute and chronic studies. Further, it also reversed PHT-induced increase in AChE activity. Conclusion: Rutin alleviated the PHT-induced cognitive impairment without compromising its antiepileptic efficacy. PMID:26729954
O’Bryant, Sid E.; Johnson, Leigh; Reisch, Joan; Edwards, Melissa; Hall, James; Barber, Robert; Devous, Michael; Royall, Donald; Singh, Meharvan
Background While a great deal of literature has focused on risk factors for Mild Cognitive Impairment (MCI), little published work examines risk for MCI among Mexican Americans. Methods Data from 1628 participants (non-Hispanic n= 1002; Mexican American n=626) were analyzed from two ongoing studies of cognitive aging and Alzheimer’s disease, Project FRONTIER and TARCC. Results When looking at the full cohorts (non-Hispanic and Mexican American), age, education, APOE ε4 status and gender were consistently related to MCI diagnosis across the two cohorts. However, when split by ethnicity advancing age was the only significant risk factor for MCI among Mexican Americans across both cohorts. Conclusions The current data suggests that many of the previously established risk factors for MCI among non-Hispanic cohorts may not be predictive of MCI among Mexican Americans and point to the need for additional work aimed at understanding factors related to cognitive aging among this underserved segment of the population. PMID:23643456
Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Khoo, Tien K; Breen, David P; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J
We evaluated the association between mild cognitive impairment (MCI) subtypes and quality of life (QoL) in 219 newly diagnosed Parkinson's disease (PD) patients without dementia. Participants completed neuropsychological tests of attention, executive function, visuospatial function, memory, and language, and reported QoL using the Parkinson's Disease Questionnaire. Impairments were most common in executive function, memory and attention. MCI subtypes were classified according to Movement Disorder Society Task Force criteria. More severe cognitive impairment was associated with poorer quality of life (p = 0.01), but subtype of impairment was not (p > 0.10), suggesting that the nature of cognitive impairment is less significant than its severity.
Buckle, M; Lee, A; Mohamed, Q; Fletcher, E; Sallam, A; Healy, R; Stratton, I; Tufail, A; Johnston, R L
Aims This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire. Methods Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system. Results The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26–39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010. Conclusion This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010. PMID:25592123
Balietti, Marta; Giuli, Cinzia; Fattoretti, Patrizia; Fabbietti, Paolo; Postacchini, Demetrio; Conti, Fiorenzo
We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A. PMID:26836161
Balietti, Marta; Giuli, Cinzia; Fattoretti, Patrizia; Fabbietti, Paolo; Postacchini, Demetrio; Conti, Fiorenzo
We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s ≥26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A.
Tricco, Andrea C.; Soobiah, Charlene; Berliner, Shirra; Ho, Joanne M.; Ng, Carmen H.; Ashoor, Huda M.; Chen, Maggie H.; Hemmelgarn, Brenda; Straus, Sharon E.
Background: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment. Methods: Our eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool. Results: We screened 15 554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini–Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] −0.22 to 0.50; Alzheimer’s Disease Assessment Scale — cognition subscale: 3 RCTs, standardized MD −0.07, 95% CI−0.16 to 0.01]) or function (Alzheimer’s Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI −0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo. Interpretation: Cognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment. PMID:24043661
Gallaway, Patrick J.; Miyake, Hiroji; Buchowski, Maciej S.; Shimada, Mieko; Yoshitake, Yutaka; Kim, Angela S.; Hongu, Nobuko
A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research. PMID:28230730
Gallaway, Patrick J; Miyake, Hiroji; Buchowski, Maciej S; Shimada, Mieko; Yoshitake, Yutaka; Kim, Angela S; Hongu, Nobuko
A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer's disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA's role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research.
Caroli, Anna; Prestia, Annapaola; Galluzzi, Samantha; Ferrari, Clarissa; van der Flier, Wiesje M.; Ossenkoppele, Rik; Van Berckel, Bart; Barkhof, Frederik; Teunissen, Charlotte; Wall, Anders E.; Carter, Stephen F.; Schöll, Michael; Choo, Il Han; Grimmer, Timo; Redolfi, Alberto; Nordberg, Agneta; Scheltens, Philip; Drzezga, Alexander
Objectives: The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non–Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI). Methods: We measured markers of amyloid pathology (CSF β-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [18F]-fluorodeoxyglucose–PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A− and N+/N− based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A−N+ cases. Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A−N−, A+N−, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N− and A+N+ groups (p ≤ 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A−N−, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N− patients did not (hazard ratio = 1.13, p = 0.771). In A+N− and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073). Conclusions: Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile. PMID:25568301
McCauley, Kathleen; Bradway, Christine; Hirschman, Karen B; Naylor, Mary D
Background Between one and two of every five hospitalized older adults have cognitive deficits, often not accurately assessed or well managed. Cognitive impairment adds substantially to the complexity of these patients’ care, places them at high risk for poor outcomes and increases the cost of health care. Methods We describe three evidence-based interventions, each capitalizing on the unique contributions of nurses and designed to improve outcomes of hospitalized older adults who have cognitive deficits. Interventions of varying intensity were compared across three hospitals (Phase I) and subsequently within the same hospitals (Phase II). All enrolled patients were screened during their index hospitalizations and cognitive deficits were communicated to relevant health care team members (Augmented Standard Care-ASC, lowest intensity). At one hospital, ASC was the only intervention. Patients at a second hospital also had care influenced by specially prepared registered nurses (Resource Nurse Care-RNC, medium intensity). Finally, patients at third hospital also received advanced practice nurse coordinated care (Transitional Care Model-TCM, higher intensity). In Phase II, newly enrolled patients at these same hospitals all received the TCM. We summarize major themes from review of multiple data sources and researcher recollections related to facilitators and barriers to implementing a complex research study. Findings Effective implementation of the three intervention strategies depended on clinician engagement and communication; degree of participation by nurses in the educational program with subsequent practice improvement; and success of advanced practice nurses in implementing the TCM with both with patients, family caregivers and clinicians. Implications Based on lessons learned in implementing complex research studies within the “real world” of clinical practice settings, recommendations focus on strengthening facilitators, minimizing barriers and gaining
Schizophrenia is associated with significant cognitive impairment. Bipolar disorder (BD) also presents with cognitive deficits that are similar to, albeit less severe, than those reported in schizophrenia. There has been controversy over whether selective deficits in social cognition or developmental trajectory of cognitive deficits can distinguish schizophrenia from BD. Also, available studies have not generally considered the potential effect of cognitive heterogeneity within the two disorders on between-group differences. The current review examines the evidence on the specificity of social cognitive deficits and early neurocognitive impairment to schizophrenia and explores the overall outcome of studies investigating within and cross-diagnosis cognitive heterogeneity in schizophrenia and BD. Current evidence does not support the specificity of social cognitive impairment to schizophrenia. Available studies also suggest that cognitive impairment in premorbid and early stages is evident not only in schizophrenia but also in many BD patients. Both schizophrenia and BD have a number of cognitive subgroups, including severe impairment, good functioning, and one or more selective or modest impairment clusters. While both disorders are represented in each cognitive subgroup, there are significant cross-diagnostic differences regarding prevalences of individuals belonging to the severe impairment and good functioning subgroups. Individuals with schizophrenia are much more likely to exhibit severe cognitive impairment than individuals with BD and good cognitive functioning is more often observed in BD patients than schizophrenia patients. Further identification of the neurobiological and genetic characteristics of the cognitive subgroups in major psychoses can improve the validity of diagnostic systems and can advance the development of personalized management approaches, including cognitive remediation.
Koch, Kathrin; Myers, Nicholas E; Göttler, Jens; Pasquini, Lorenzo; Grimmer, Timo; Förster, Stefan; Manoliu, Andrei; Neitzel, Julia; Kurz, Alexander; Förstl, Hans; Riedl, Valentin; Wohlschläger, Afra M; Drzezga, Alexander; Sorg, Christian
Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD.
Zebehazy, Kim T.
This study reports opinions and practices of teachers of students with visual impairments (TSVIs) in 34 states regarding functional literacy for students with visual impairments (VIs) and significant cognitive disabilities (SCDs). The survey asked TSVIs to select a definition of functional literacy, indicate agreement with a series of literacy…
Garand, Linda; Dew, Mary Amanda; Urda, Bridget; Lingler, Jennifer Hagerty; DeKosky, Steven T.; Reynolds, Charles F.
The behavioral changes in people with dementia often negatively affect marital relationships. Yet little is known about how the marital relationship is affected when the care recipient has mild cognitive impairment (MCI). This study characterizes marital quality among adults who live with a spouse with MCI. Data were drawn from interviews with 27 spouses of people with a recent diagnosis of MCI. Even at early stages of MCI, many spouses report the frequent occurrence of distressing behaviors. This study demonstrates that MCI may degrade the quality of the marital relationship. These results have implications for clinical practice and the delivery of health care and social services to these families. It is important to develop interventions to address the needs of these individuals and their caregivers. Results of this study suggest the need for mental health interventions designed to preserve the quality of these marital relationships. PMID:17984481
Caffarra, Paolo; Ghetti, Caterina; Concari, Letizia; Venneri, Annalena
In this study the regional cerebral blood flow (rCBF) pattern of three Mild Cognitive Impairment (MCI) subtypes was measured with SPECT in 60 patients (nineteen with an amnestic deficit, sixteen with disexecutive deficits, and twenty five with mild multidomain deficits) and compared with that of 15 healthy matched older adults. The amnestic MCI subgroup showed significant hypoperfusion in the left hippocampus, parahippocampal gyrus and fronto-parieto-temporal areas. The disexecutive subgroup had significant hypoperfusion of the left superior, medial frontal and cingulate cortex. The multidomain subgroup had similar perfusion deficits to the amnestic subgroup, with an additional deficit in the left posterior cingulate gyrus. This study found differential patterns of hypoperfusion in MCI subtypes. Since all patients who progressed to dementia converted to probable Alzheimer’s disease, the different rCBF patterns most likely reflect the neuropathological heterogeneity at onset and differences in disease stage. PMID:19018314
Bucholtz, Nina; Demuth, Ilja
While the pathogenesis of the sporadic form of Alzheimer disease (late onset Alzheimer disease, LOAD) is not fully understood, it seems to be clear that a combination of genetic and environmental factors are involved and influence the course of the disease. Among these factors, elevated levels of oxidative stress have been recognized and individual differences in the capacity to deal with DNA damage caused by its effects have been the subject of numerous studies. This review summarizes the research on DNA repair proteins and genes in the context of LOAD pathogenesis and its possible prodromal stage, mild cognitive impairment (MCI). The current status of the research in this field is discussed with respect to methodological issues which might have compromised the outcome of some studies and future directions of investigation on this subject are depicted.
Bocanegra, Yamile; García, Adolfo M; Lopera, Francisco; Pineda, David; Baena, Ana; Ospina, Paula; Alzate, Diana; Buriticá, Omar; Moreno, Leonardo; Ibáñez, Agustín; Cuetos, Fernando
Parkinson's disease (PD) patients show marked impairments in processing action verbs, and to a lesser extent, concrete (specially, manipulable) nouns. However, it is still unclear to what extent deficits in each of these categories are influenced by more general cognitive dysfunctions, and whether they are modulated by the words' implied motility. To examine these issues, we evaluated 49 non-demented PD patients and 49 healthy volunteers in an oral production task. The patients were divided into two groups depending on the presence or absence of mild cognitive impairment (PD-MCI and PD-nMCI, respectively). Participants named pictures of actions varying in motion content (low and high) and of objects varying in manipulability (low and high). The PD-MCI group showed deficits across all four categories. However, PD-nMCI patients exhibited a selective difficulty for high-motion action verbs. This finding corroborates and refines previous results suggesting that disturbances of action-related lexico-semantic information in PD constitute a sui generis alteration manifested early in the course of the disease's physiopathology. Moreover, it suggests that the grounding of action verbs on motor circuits could depend on fine-grained intracategorical semantic distinctions.
Bhattacharjee, Atanu; Shashidhara, Shastry Chakrakodi; Saha, Santanu
Loss of cognition is one of the age related mental problems and a characteristic symptom of neurodegenerative disorders like Alzheimer’s. Crataeva nurvala Buch-Ham, a well explored traditional Indian medicinal plant of Westernghats, is routinely used as folkloric medicine to treat various ailments in particular urolithiasis and neurological disorders associated with cognitive dysfunction. The objective of the study was to evaluate the nootropic activity of Crataeva nurvala Buch-Ham stem bark in different learning and memory paradigm viz. Elevated plus maze and Y-maze against scopolamine induced cognitive impairment. Moreover, to elucidate possible mechanism, we studied the influence of Crataeva nurvala ethanolic extract on central cholinergic activity via estimating the whole brain acetyl cholinesterase enzyme. Ethanolic extracts of Crataeva nurvala (100, 200 and 400 mg/kg body weight) were administered to adult Wistar rats for successive seven days and the acquisition, retention and retrieval of spatial recognition memory was determined against scopolamine (1 mg/kg, i.p.) induced amnesia through exteroceptive behavioral models viz. Elevated plus maze and Y-maze models. Further, whole brain acetyl cholinesterase enzyme was estimated through Ellman’s method. Pretreatment with Crataeva nurvala ethanolic extract significantly improved spatial learning and memory against scopolamine induced amnesia. Moreover, Crataeva nurvala extract decreased rat brain acetyl cholinesterase activity in a dose dependent manner and comparable to the standard drug Piracetam. The results indicate that ethanolic extract of Crataeva nurvala might be a useful as nootropic agent to delay the onset and reduce the severity of symptoms associated with dementia and Alzheimer’s disease. The underlying mechanism of action of its nootropic potentiality might be attributed to its anticholinesterase property. PMID:27065767
Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang
Identification of subjects at the early stages of Alzheimer’s disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%–17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features. PMID:28243102
Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang
Identification of subjects at the early stages of Alzheimer's disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%-17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features.
Rickenbach, Elizabeth Hahn; Condeelis, Kristen L; Haley, William E
Daily experiences of stress are common and have been associated with worse affect among older adults. People with mild cognitive impairment (PWMCI) have measurable memory deficits in between normal cognition and dementia and have been identified as having greater psychological distress than cognitively healthy older adults (CHOAs). Little is known about whether daily stressors contribute to distress among PWMCI. We hypothesized that compared with CHOAs, PWMCI would have higher daily negative affect and lower daily positive affect, report greater numbers and severity of daily stressors, and experience greater emotional reactivity to daily stressors. Fifteen clinically diagnosed PWMCI and 25 CHOAs completed daily reports of stressors, stressor severity, and positive and negative affect over an 8-day period. PWMCI reported higher daily negative affect, lower daily positive affect, and higher numbers and greater severity of memory stressors but did not differ from CHOAs in numbers or severity of general stressors. Cognitive status was a moderator of the daily stress-affect relationship. Days with greater numbers and severity of general daily stressors were associated with higher negative affect only for PWMCI. The numbers and severity of memory stressors were not associated with negative affect. In addition, more severe general daily stressors and memory stressors were associated with lower positive affect for all participants. Results suggest that PWMCI are less resilient in the face of daily stress than are CHOAs in terms of negative affect, perhaps because of declines in reserve capacity. The study presents a promising approach to understanding stress and coping in predementia states of cognition.
Grosso, G; Estruch, R
Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.
Alahmadi, Hanin H; Shen, Yuan; Fouad, Shereen; Luft, Caroline Di B; Bentham, Peter; Kourtzi, Zoe; Tino, Peter
Early diagnosis of dementia is critical for assessing disease progression and potential treatment. State-or-the-art machine learning techniques have been increasingly employed to take on this diagnostic task. In this study, we employed Generalized Matrix Learning Vector Quantization (GMLVQ) classifiers to discriminate patients with Mild Cognitive Impairment (MCI) from healthy controls based on their cognitive skills. Further, we adopted a "Learning with privileged information" approach to combine cognitive and fMRI data for the classification task. The resulting classifier operates solely on the cognitive data while it incorporates the fMRI data as privileged information (PI) during training. This novel classifier is of practical use as the collection of brain imaging data is not always possible with patients and older participants. MCI patients and healthy age-matched controls were trained to extract structure from temporal sequences. We ask whether machine learning classifiers can be used to discriminate patients from controls and whether differences between these groups relate to individual cognitive profiles. To this end, we tested participants in four cognitive tasks: working memory, cognitive inhibition, divided attention, and selective attention. We also collected fMRI data before and after training on a probabilistic sequence learning task and extracted fMRI responses and connectivity as features for machine learning classifiers. Our results show that the PI guided GMLVQ classifiers outperform the baseline classifier that only used the cognitive data. In addition, we found that for the baseline classifier, divided attention is the only relevant cognitive feature. When PI was incorporated, divided attention remained the most relevant feature while cognitive inhibition became also relevant for the task. Interestingly, this analysis for the fMRI GMLVQ classifier suggests that (1) when overall fMRI signal is used as inputs to the classifier, the post
Alahmadi, Hanin H.; Shen, Yuan; Fouad, Shereen; Luft, Caroline Di B.; Bentham, Peter; Kourtzi, Zoe; Tino, Peter
Early diagnosis of dementia is critical for assessing disease progression and potential treatment. State-or-the-art machine learning techniques have been increasingly employed to take on this diagnostic task. In this study, we employed Generalized Matrix Learning Vector Quantization (GMLVQ) classifiers to discriminate patients with Mild Cognitive Impairment (MCI) from healthy controls based on their cognitive skills. Further, we adopted a “Learning with privileged information” approach to combine cognitive and fMRI data for the classification task. The resulting classifier operates solely on the cognitive data while it incorporates the fMRI data as privileged information (PI) during training. This novel classifier is of practical use as the collection of brain imaging data is not always possible with patients and older participants. MCI patients and healthy age-matched controls were trained to extract structure from temporal sequences. We ask whether machine learning classifiers can be used to discriminate patients from controls and whether differences between these groups relate to individual cognitive profiles. To this end, we tested participants in four cognitive tasks: working memory, cognitive inhibition, divided attention, and selective attention. We also collected fMRI data before and after training on a probabilistic sequence learning task and extracted fMRI responses and connectivity as features for machine learning classifiers. Our results show that the PI guided GMLVQ classifiers outperform the baseline classifier that only used the cognitive data. In addition, we found that for the baseline classifier, divided attention is the only relevant cognitive feature. When PI was incorporated, divided attention remained the most relevant feature while cognitive inhibition became also relevant for the task. Interestingly, this analysis for the fMRI GMLVQ classifier suggests that (1) when overall fMRI signal is used as inputs to the classifier, the post
Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo
Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging.
Waring, J D; Dimsdale-Zucker, H R; Flannery, S; Budson, A E; Kensinger, E A
Young and older adults experience benefits in attention and memory for emotional compared to neutral information, but this memory benefit is greatly diminished in Alzheimer's disease (AD). Little is known about whether this impairment arises early or late in the time course between healthy aging and AD. This study compared memory for positive, negative, and neutral items with neutral backgrounds between patients with mild cognitive impairment (MCI) and healthy older adults. We also used a divided attention condition in older adults as a possible model for the deficits observed in MCI patients. Results showed a similar pattern of selective memory for emotional items while forgetting their backgrounds in older adults and MCI patients, but MCI patients had poorer memory overall. Dividing attention during encoding disproportionately reduced memory for backgrounds (versus items) relative to a full attention condition. Participants performing in the lower half on the divided attention task qualitatively and quantitatively mirrored the results in MCI patients. Exploratory analyses comparing lower- and higher-performing MCI patients showed that only higher-performing MCI patients had the characteristic scene memory pattern observed in healthy older adults. Together, these results suggest that the effects of emotion on memory are relatively well preserved for patients with MCI, although emotional memory patterns may start to be altered once memory deficits become more pronounced.
Seidenberg, Michael; Guidotti, Leslie; Nielson, Kristy A.; Woodard, John L.; Durgerian, Sally; Zhang, Qi; Gander, Amelia; Antuono, Piero; Rao, Stephen M.
Person identification represents a unique category of semantic knowledge that is commonly impaired in Alzheimer's Disease (AD), but has received relatively little investigation in patients with Mild Cognitive Impairment (MCI). The current study examined the retrieval of semantic knowledge for famous names from three time epochs (recent, remote, and enduring) in two participant groups; 23 aMCI patients and 23 healthy elderly controls. The aMCI group was less accurate and produced less semantic knowledge than controls for famous names. Names from the enduring period were recognized faster than both recent and remote names in both groups, and remote names were recognized more quickly than recent names. Episodic memory performance was correlated with greater semantic knowledge particularly for recent names. We suggest that the anterograde memory deficits in the aMCI group interferes with learning of recent famous names and as a result produces difficulties with updating and integrating new semantic information with previously stored information. The implications of these findings for characterizing semantic memory deficits in MCI are discussed. PMID:19128524
Seidenberg, Michael; Guidotti, Leslie; Nielson, Kristy A; Woodard, John L; Durgerian, Sally; Zhang, Qi; Gander, Amelia; Antuono, Piero; Rao, Stephen M
Person identification represents a unique category of semantic knowledge that is commonly impaired in Alzheimer's disease (AD), but has received relatively little investigation in patients with mild cognitive impairment (MCI). The current study examined the retrieval of semantic knowledge for famous names from three time epochs (recent, remote, and enduring) in two participant groups: 23 amnestic MCI (aMCI) patients and 23 healthy elderly controls. The aMCI group was less accurate and produced less semantic knowledge than controls for famous names. Names from the enduring period were recognized faster than both recent and remote names in both groups, and remote names were recognized more quickly than recent names. Episodic memory performance was correlated with greater semantic knowledge particularly for recent names. We suggest that the anterograde memory deficits in the aMCI group interferes with learning of recent famous names and as a result produces difficulties with updating and integrating new semantic information with previously stored information. The implications of these findings for characterizing semantic memory deficits in MCI are discussed. (JINS, 2009, 15, 9-18.).
Kiddoe, Jared M; Whitfield, Keith E; Andel, Ross; Edwards, Christopher L
This article compared and contrasted the Telephone Interview of Cognitive Status (TICS) to the racially-sensitive Short Portable Mental Status Questionnaire (SPMSQ). The empirical questions addressed was whether the TICS over-represented African American (AA) cognitive impairment (CI) relative to the SPMSQ, if there were age differences in CI prevalence between younger subjects (ages 50-64) and older ones (>64 years) and on accuracy to detect CI in individuals with higher levels of educations (> or =13 years) versus those with lower education levels (<13 years). A secondary data analysis was performed on 396 AA participants from the Carolina African American Twin Study on Aging (CAATSA). The SPMSQ measured CI prevalence at 10.3% and the TICS at 45.0%. Within the younger group, TICS and CI prevalence was 49.3 and 80% among the older group. Within the younger group SPMSQ and CI prevalence was 14.5 and 53.8% among the older group. Within the higher educated group, TICS and CI prevalence was 36.7 and 51.4% among the lower educated. Within the higher educated group, SPMSQ and CI prevalence was 7.7 and 14.5% among the lower educated. Findings are consistent with our hypotheses that the TICS would be a less accurate assessor of CI among AAs.
Kashefpoor, Masoud; Rabbani, Hossein; Barekatain, Majid
Alzheimer's disease (AD) is one of the most expensive and fatal diseases in the elderly population. Up to now, no cure have been found for AD, so early stage diagnosis is the only way to control it. Mild cognitive impairment (MCI) usually is the early stage of AD which is defined as decreasing in mental abilities such a cognition, memory, and speech not too severe to interfere daily activities. MCI diagnosis is rather hard and usually assumed as normal consequences of aging. This study proposes an accurate, mobile, and nonexpensive diagnostic approach based on electroencephalogram (EEG) signal. EEG signals were recorded using 19 electrodes positioned according to the 10–20 International system at resting eyes closed state from 16 normal and 11 MCI participants. Nineteen Spectral features are computed for each channel and examined using a correlation based algorithm to select the best discriminative features. Selected features are classified using a combination of neurofuzzy system and k-nearest neighbor classifier. Final results reach 88.89%, 100%, and 83.33% for accuracy, sensitivity, and specificity, respectively, which shows the potential of proposed method to be used as an MCI diagnostic tool, especially for screening a large population. PMID:27014609
Narayanan, Leela; Murray, Alison Dorothy
Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer’s disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia. PMID:27029053
Ren, Xiaojia; St Clair, Daret K; Butterfield, D Allan
One of the major complaints patients who survive cancer often make is chemotherapy induced cognitive impairment (CICI), which survivors often call "chemo brain." CICI is a side effect of chemotherapy due to the cytotoxicity and neurotoxicity of anti-cancer drugs causing structural and functional changes in brain, even when drugs that do not cross the blood brain barrier (BBB) are used. Diminished cognitive functions including diminution of learning and memory, concentration and attention, processing speed and executive functions that reduce quality of life and ability to work are common signs and symptoms of CICI. There still is not a clarified and complete mechanism for CICI, but researchers have pointed to several biochemical candidates. Chemotherapy-induced, cytokine-mediated involvement in CICI will be mainly discussed in this review paper with emphasis on different types of cytokines, correlated with BBB and epigenetic changes. Mechanisms of ROS-generating, anti-cancer drugs and their relation to cytokine-mediated CICI will be emphasized.
Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe
Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD.
Mitolo, Micaela; Gardini, Simona; Fasano, Fabrizio; Crisi, Girolamo; Pelosi, Annalisa; Pazzaglia, Francesca; Caffarra, Paolo
Spatial abilities decline in normal aging and decrease faster and earlier in Alzheimer's disease (AD), but these deficits are under investigated. The main goals of this study were to assess visuospatial memory abilities in mild cognitive impairment (MCI), in order to verify whether these tasks might be valid as the standard cognitive test to differentiate MCI individuals from normal controls and to investigate the brain structural correlates of visuospatial deficits. Twenty MCI patients and fourteen healthy elderly controls underwent an experimental visuospatial battery, which also included self-rating spatial questionnaires, and structural MRI brain imaging. Compared to healthy elderly controls, MCI patients scored significantly worse in almost all visuospatial tasks. ROC analysis showed that visuospatial tasks had an elevated discriminant power between groups (AUC >0.90). Voxel-based morphometry analysis, compared to controls, disclosed a higher level of atrophy in frontal and medio-temporal regions and a different pattern of correlation between grey matter values and visuospatial performance, with wider distributed areas of the occipital and middle temporal cortex in the map and route learning. This study indicates that visuospatial memory tests are valid tools in completing the diagnostic evaluation of MCI.
Zhang, Jiabei; Piwowar, Nathan; Reilly, Coleen Jennifer
The purpose of this investigation was to analyze the physical fitness performance of young adults with and without cognitive impairments. Participants were 75 young adults, including 41 without disabilities (23 females, 18 males; M of age = 21.88) and 34 with mild cognitive impairments (14 females, 20 males; M of age = 21.79). They received…
Wittich, Walter; Phillips, Natalie; Nasreddine, Ziad S.; Chertkow, Howard
Evaluating the cognitive status of individuals who are visually impaired is limited by the design of the test that is used. This article presents data on the sensitivity and specificity of the version of the Montreal Cognitive Assessment for people who are visually impaired. The original validation data were reanalyzed, excluding the five visual…
Lucas, Marcella M.; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L.; Scott, Rod C.
One of the most common and serious co-morbidities in patients with epilepsy is cognitive impairment. While early-life seizures are considered a major cause for cognitive impairment, it is not known whether it is the seizures, the underlying neurological substrate or a combination that has the largest impact on eventual learning and memory. Teasing…
Noel, Margaret A
Transitions in care settings can be disconcerting to anyone, but they can be particularly difficult for people with cognitive impairment. MemoryCare's design of integrated clinical and care management services is well suited to minimizing the preventable morbidity that can accompany transitions in health care for cognitively impaired older adults at high risk for poor outcomes.
Adebiyi, Akindele O.; Ogunniyi, Adesola; Adediran, Babatunde A.; Olakehinde, Olaide O.; Siwoku, Akeem A.
Background: Vascular risk models can be quite informative in assisting the clinician to make a prediction of an individual's risk of cognitive impairment. Thus, a simple marker is a priority for low-capacity settings. This study examines the association of selected simple to deploy vascular markers with cognitive impairment in an elderly…
25-hydroxyvitamin D (25[OH]D) deficiency and cognitive impairment are both prevalent in hemodialysis patients in the United States. This study tested the hypothesis that 25(OH)D deficiency may be associated with cognitive impairment because of its vasculoprotective, neuroprotective, and immune-modul...
Adams, Wendy L.; McIlvain, Helen E.; Geske, Jenenne A.; Porter, Judy L.
Purpose: This study aims to develop ah in-depth understanding of the issues important to primary care physicians in providing care to cognitively impaired elders. Design and Methods: In-depth interviews were conducted with 20 primary care physicians. Text coded as "cognitive impairment" was retrieved and analyzed by use of grounded theory analysis…
Buhlmann, Ulrike; Deckersbach, Thilo; Engelhard, Iris; Cook, Laura M; Rauch, Scott L; Kathmann, Norbert; Wilhelm, Sabine; Savage, Cary R
Individuals with obsessive-compulsive disorder (OCD) have difficulties in organizing information during encoding associated with subsequent memory impairments. This study was designed to investigate whether impairments in organization in individuals with OCD can be alleviated with cognitive training. Thirty-five OCD subjects and 36 controls copied and recalled the Rey-Osterrieth Complex Figure Test (RCFT) [Osterrieth, P.A., 1944. Le test de copie d'une figure complexe: Contribution a l'étude de la perception et de la memoire (The test of copying a complex figure: A contribution to the study of perception and memory). Archive de Psychologie 30, 286-350.] before being randomly assigned to a training or non-training condition. The training condition was designed to improve the ability to organize complex visuospatial information in a meaningful way. The intervention phase was followed by another copy and recall trial of the RCFT. Both OCD and control subjects who underwent training improved more in organization and memory than subjects who did not receive organizational training, providing evidence that the training procedure was effective. OCD subjects improved more in organizational during encoding than control subjects, irrespective of whether or not they had received training. This suggests that organization impairment in OCD affects primarily the ability to spontaneously utilize strategies when faced with complex, ambiguous information but that the ability to implement such strategies when provided with additional trials is preserved. These findings support a distinction in OCD between failure to utilize a strategy and incapacity to implement a strategy.
Sachdev, Perminder S.; Lipnicki, Darren M.; Crawford, John; Reppermund, Simone; Kochan, Nicole A.; Trollor, Julian N.; Wen, Wei; Draper, Brian; Slavin, Melissa J.; Kang, Kristan; Lux, Ora; Mather, Karen A.; Brodaty, Henry; Team, Ageing Study
Introduction Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition. Methods Our analyses considered 223 participants (48.9% male) aged 71–89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors. Results There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p = 0.026). Discussion Numerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of
Roberts, Rosebud O.; Geda, Yonas E.; Knopman, David S.; Christianson, Teresa J.H.; Pankratz, V. Shane; Kullo, Iftikhar J.; Petersen, Ronald C.
Background Inflammation is suggested to play a role in the development of Alzheimer’s disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample. Methods Olmsted County, MN, residents aged 70–89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis alpha (TNFα), and adiponectin were measured at baseline. Results Among 313 subjects with MCI and 1,570 cognitively normal subjects, a CRP level in the upper quartile (> 3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00–2.01) and with non-amnestic MCI (na-MCI; OR, 2.05; 95% CI, 1.12–3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (a-MCI; OR, 1.21; 95% CI, 0.81–1.82). No association was observed with the other inflammatory markers. Conclusions Plasma CRP is associated with prevalent MCI and with na-MCI in elderly, non-demented persons in the population-based setting. These findings suggest an involvement of inflammation in the pathogenesis of MCI. PMID:19751919
Bertrams, Alex; Baumeister, Roy F.; Englert, Chris
We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests. PMID:27065013
Coppola, Vincent J; Hough, Gerald; Bingman, Verner P
The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.
Mine, Masashi; Miyata, Kimie; Morikawa, Masayuki; Nishi, Tomo; Okamoto, Nozomi; Kawasaki, Ryo; Yamashita, Hidetoshi; Kurumatani, Norio; Ogata, Nahoko
Both visual impairment and cognitive impairment are essential factors that determine the quality of life in the aged population. The aim of this study was to determine if a correlation existed between visual acuity and cognitive impairment in an elderly Japanese population. The Fujiwara-kyo Eye Study was a cross-sectional study of individuals aged ≥68 years who lived in Nara Prefecture of Japan. Participants underwent ophthalmological examinations and cognitive function test. A mild visual impairment was defined as having a best corrected visual acuity (BCVA) >0.2 logarithm of the minimum angle of resolution (logMAR) units in the better eye. Cognitive impairment was defined as having a Mini-Mental State Examination (MMSE) score of ≤23 points. A total to 2818 individuals completed the examinations. The mean age of the participants was 76.3 ± 4.8 years (mean ± standard deviation). The mean BCVA of the better eye was -0.02 ± 0.13 logMAR units and 6.6% subjects were classified as being mildly visually impaired. The mean MMSE score was 27.3 ± 2.3 and 5.7% subjects were classified as being cognitively impaired. The proportion of subjects with cognitive or moderate visual impairment increased with age, and there was a significant correlation between the visual acuity and MMSE score (r = -0.10, p < 0.0001). Subjects with mild visual impairments had 2.4 times higher odds of having cognitive impairment than those without visual impairment (odds ratio 2.4, 95% confidence interval, 1.5-3.8, p < 0.001) after adjusting for age, sex, and length of education. We conclude that it may be important to maintain good visual acuity to reduce the risk of having cognitive impairment.
de Paula, Jonas Jardim; Cintra, Marco Túlio Gualberto; Miranda, Débora Marques; Bicalho, Maria Aparecida Camargos; Moares, Edgar Nunes; Malloy-Diniz, Leandro Fernandes
Mild cognitive impairment is a clinical condition more frequent in patients with Parkinson's disease than in general population. The nonamnestic presentations, usually characterized by executive dysfunction, are most prevalent. We present a case report of a Parkinson's disease patient diagnosed with nonamnestic mild cognitive impairment that showed complete remission of cognitive symptoms after one year. We discuss the possible causes for the remission, focusing on the treatment of medical conditions such as a major depressive episode and vitamin B12 deficiency, in addition to the change of pharmacological treatment. In a third assessment, cognitive performance remained normal. The case report highlights the importance of controlling clinical comorbidities on the assessment and followup of mild cognitive impairment, especially on Parkinson's disease. PMID:23193494
de Paula, Jonas Jardim; Cintra, Marco Túlio Gualberto; Miranda, Débora Marques; Bicalho, Maria Aparecida Camargos; Moares, Edgar Nunes; Malloy-Diniz, Leandro Fernandes
Mild cognitive impairment is a clinical condition more frequent in patients with Parkinson's disease than in general population. The nonamnestic presentations, usually characterized by executive dysfunction, are most prevalent. We present a case report of a Parkinson's disease patient diagnosed with nonamnestic mild cognitive impairment that showed complete remission of cognitive symptoms after one year. We discuss the possible causes for the remission, focusing on the treatment of medical conditions such as a major depressive episode and vitamin B12 deficiency, in addition to the change of pharmacological treatment. In a third assessment, cognitive performance remained normal. The case report highlights the importance of controlling clinical comorbidities on the assessment and followup of mild cognitive impairment, especially on Parkinson's disease.
Moura, Daniela Silva; Sultan, Serge; Georgin-Lavialle, Sophie; Barete, Stéphane; Lortholary, Olivier; Gaillard, Raphael; Hermine, Olivier
Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition.
Prakash, RS; Snook, EM; Lewis, JM; Motl, RW; Kramer, AF
There is debate in the literature regarding the magnitude, nature, and influence of cognitive impairment in individuals with relapsing-remitting multiple sclerosis (RRMS), Therefore, we conducted a meta-analysis that quantified the overall magnitude of cognitive impairment in individuals with RRMS and identified the domains of cognition and clinical/demographic variables that were moderators of the overall effect. We included 57 studies with 3891 participants that yielded a total of 755 effect sizes. Overall, there was a moderate decline in cognitive functioning in individuals with RRMS compared with healthy controls. Larger effects were observed in cognitive domains of motor functioning, mood status and memory and learning. Regarding demographic and clinical variables, age and gender were moderators of cognitive impairment in all cognitive domains, whereas neurological disability and disease duration primarily moderated performance on tasks assessing memory and learning. PMID:18701571
Lemos, Raquel; Afonso, Ana; Martins, Cristina; Waters, James H; Blanco, Filipe Sobral; Simões, Mário R; Santana, Isabel
The Selective Reminding Test (SRT) and the Free and Cued Selective Reminding Test (FCSRT) are multitrial memory tests that use a common "selective reminding" paradigm that aims to facilitate learning by presenting only the missing words from the previous recall trial. While in the FCSRT semantic cues are provided to elicit recall, in the SRT, participants are merely reminded of the missing items by repeating them. These tests have been used to assess age-related memory changes and to predict dementia. The performance of healthy elders on these tests has been compared before, and results have shown that twice as many words were retrieved from long-term memory in the FCSRT compared with the SRT. In this study, we compared the tests' properties and their accuracy in discriminating amnestic mild cognitive impairment (aMCI; n = 20) from Alzheimer disease (AD; n = 18). Patients with AD performed significantly worse than patients with aMCI on both tests. The percentage of items recalled during the learning trials was significantly higher for the FCSRT in both groups, and a higher number of items were later retrieved, showing the benefit of category cueing. Our key finding was that the FCSRT showed higher accuracy in discriminating patients with aMCI from those with AD.
Hindle, John V
Parkinson's disease (PD) has been described as an age-related disease. Ageing significantly increases the risk of psychosis and dementia. Older patients often have a complex mixture of delirium, psychosis, dementia, gait and balance problems and other comorbidities which can cause significant management problems. There are concerns about the safety and tolerability of the treatments for psychosis and dementia. Delirium is common in older Parkinson's patients and must be assessed and managed carefully. The aetiology of psychosis in Parkinson's is complex and often associated with the development of cognitive impairment. Initial adjustments of Parkinson's drugs should be considered if symptoms are intrusive. Where drug therapy is required, evidence suggests that quetiapine may be a safe initial option. There is no contraindication to the use of clozapine in older patients, with the required blood monitoring. Dementia is almost inevitable with very advanced disease and increasing age, and is associated with a marked cholinergic deficit in the brain. Cholinesterase inhibitors may be more effective in PD than in Alzheimer's disease and appear relatively safe with appropriate monitoring of the pulse. There is much less evidence for the use of memantine. There is no current evidence for the use of specific non-pharmacological therapies in the management of psychosis or dementia in PD. Due to the associated gait and balance problems, older Parkinson's patients benefit from comprehensive multi-disciplinary assessment.
Volosin, Márta; Janacsek, Karolina; Németh, Dezső
Mild cognitive impairment (MCI) can be considered as an intermediate stage between normal cognitive aging and dementia. Its screening is extremely important because within a year in 15-20% of cases dementia can evolve. In Hungary, the most widely used screening tool for both dementia and MCI is the Mini Mental State Examination (MMSE), which is often criticized for its poor screening sensitivity of mild dementia and MCI. To eliminate this problem, the Montreal Cognitive Assessment (MoCA) was developed, especially for screening MCI. Our study presents the first results with the Hungarian translation of MoCA. We used Beck Depression Inventory (BDI) for controlling depression. In MoCA the cutoff score between healthy and MCI persons was 24 out of 30. MoCA was more sensitive in detecting MCI than MMSE and its inner consistency was also slightly higher. Specificity of the tests to detect MCI was similar. The results on BDI were not related to either MoCA or MMSE. Our results suggest that MoCA can be a useful tool to detect cognitive decline.
Oliveira, Luciana; Graeff, Frederico G.; Pereira, Silvia R. C.; Oliveira-Silva, Ieda F.; Franco, Glaura C.
Emotion and spatial cognitive aspects were assessed in adult and middle-aged rats using the elevated T-maze (ETM) and the Morris water maze (MWM) tasks. Both adult and middle-aged rats were able to acquire inhibitory avoidance behaviour, though the middle-aged subjects showed larger latencies along the trials, including the baseline, which was significantly longer than that showed by adult rats. Further, compared to adult rats, middle-aged rats had longer escape latency. In spite of the worse performance in the second session of the spatial cognitive task, the middle-aged rats were able to learn the task and remember the information along the whole probe trial test. Both thalamic serotonin (5-HT) concentration and amygdala serotonergic activity (5-HIAA/5-HT) are significantly correlated, respectively, to escape latency and behavioural extinction in the MWM only for middle-aged rats. A significant correlation between the 5-HIAA/5-HT ratio in the amygdala and behavioural extinction for middle-aged, but not for adult, rats was observed. This result suggests that serotonergic activity in the amygdala may regulate behavioural flexibility in aged animals. In addition, a significant negative correlation was found between hippocampal 5-HIAA/5-HT ratio and the path length at the second training session of the MWM task, although only for adult subjects. This was the only session where a significant difference between the performance of middle-aged and adult rats has occurred. Although the involvement of the hippocampus in learning and memory is well established, the present work shows, for the first time, a correlation between a serotonergic hippocampal parameter and performance of a spatial task, which is lost with ageing. PMID:20431986
Serpa, R. F. B.; de Jesus, E. F. O.; Anjos, M. J.; Lopes, R. T.; do Carmo, M. G. T.; Rocha, M. S.; Rodrigues, L. C.; Moreira, S.; Martinez, A. M. B.
In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied.
John, Tami; Lomeli, Naomi; Bota, Daniela A
Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15-50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age.
Lomeli, Naomi; Bota, Daniela A.
Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15–50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age. PMID:27851909
Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong
Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI. PMID:27630562
Fiorenzato, Eleonora; Weis, Luca; Seppi, Klaus; Onofrj, Marco; Cortelli, Pietro; Zanigni, Stefano; Tonon, Caterina; Kaufmann, Horacio; Shepherd, Timothy Michael; Poewe, Werner; Krismer, Florian; Wenning, Gregor; Antonini, Angelo; Biundo, Roberta
Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of "subcortical cognitive impairment".
Volkers, K. M.; Scherder, E. J. A.
Background. Physical performances and cognition are positively related in cognitively healthy people. The aim of this study was to examine whether physical performances are related to specific cognitive functioning in older people with mild to severe cognitive impairment. Methods. This cross-sectional study included 134 people with a mild to severe cognitive impairment (mean age 82 years). Multiple linear regression was performed, after controlling for covariates and the level of global cognition, with the performances on mobility, strength, aerobic fitness, and balance as predictors and working memory and episodic memory as dependent variables. Results. The full models explain 49–57% of the variance in working memory and 40–43% of episodic memory. Strength, aerobic fitness, and balance are significantly associated with working memory, explaining 3–7% of its variance, irrespective of the severity of the cognitive impairment. Physical performance is not related to episodic memory in older people with mild to severe cognitive impairment. Conclusions. Physical performance is associated with working memory in older people with cognitive impairment. Future studies should investigate whether physical exercise for increased physical performance can improve cognitive functioning. This trial is registered with ClinicalTrials.gov NTR1482. PMID:24757674
Li, Yang; Wee, Chong-Yaw; Jie, Biao; Peng, Ziwen; Shen, Dinggang
Brain connectivity network derived from functional magnetic resonance imaging (fMRI) is becoming increasingly prevalent in the researches related to cognitive and perceptual processes. The capability to detect causal or effective connectivity is highly desirable for understanding the cooperative nature of brain network, particularly when the ultimate goal is to obtain good performance of control-patient classification with biological meaningful interpretations. Understanding directed functional interactions between brain regions via brain connectivity network is a challenging task. Since many genetic and biomedical networks are intrinsically sparse, incorporating sparsity property into connectivity modeling can make the derived models more biologically plausible. Accordingly, we propose an effective connectivity modeling of resting-state fMRI data based on the multivariate autoregressive (MAR) modeling technique, which is widely used to characterize temporal information of dynamic systems. This MAR modeling technique allows for the identification of effective connectivity using the Granger causality concept and reducing the spurious causality connectivity in assessment of directed functional interaction from fMRI data. A forward orthogonal least squares (OLS) regression algorithm is further used to construct a sparse MAR model. By applying the proposed modeling to mild cognitive impairment (MCI) classification, we identify several most discriminative regions, including middle cingulate gyrus, posterior cingulate gyrus, lingual gyrus and caudate regions, in line with results reported in previous findings. A relatively high classification accuracy of 91.89 % is also achieved, with an increment of 5.4 % compared to the fully-connected, non-directional Pearson-correlation-based functional connectivity approach.
Li, Yang; Wee, Chong-Yaw; Jie, Biao; Peng, Ziwen
Brain connectivity network derived from functional magnetic resonance imaging (fMRI) is becoming increasingly prevalent in the researches related to cognitive and perceptual processes. The capability to detect causal or effective connectivity is highly desirable for understanding the cooperative nature of brain network, particularly when the ultimate goal is to obtain good performance of control-patient classification with biological meaningful interpretations. Understanding directed functional interactions between brain regions via brain connectivity network is a challenging task. Since many genetic and biomedical networks are intrinsically sparse, incorporating sparsity property into connectivity modeling can make the derived models more biologically plausible. Accordingly, we propose an effective connectivity modeling of resting-state fMRI data based on the multivariate autoregressive (MAR) modeling technique, which is widely used to characterize temporal information of dynamic systems. This MAR modeling technique allows for the identification of effective connectivity using the Granger causality concept and reducing the spurious causality connectivity in assessment of directed functional interaction from fMRI data. A forward orthogonal least squares (OLS) regression algorithm is further used to construct a sparse MAR model. By applying the proposed modeling to mild cognitive impairment (MCI) classification, we identify several most discriminative regions, including middle cingulate gyrus, posterior cingulate gyrus, lingual gyrus and caudate regions, in line with results reported in previous findings. A relatively high classification accuracy of 91.89 % is also achieved, with an increment of 5.4 % compared to the fully-connected, non-directional Pearson-correlation-based functional connectivity approach. PMID:24595922
Puente, Antonio Nicolas; Terry, Douglas P; Faraco, Carlos C; Brown, Courtney L; Miller, L Stephen
Older adults (OAs) with mild cognitive impairment (MCI) are traditionally thought to have preservation of activities of daily living (ADLs). However, recent evidence suggests OAs with MCI may have difficulty completing ADLs and specifically instrumental ADLs (IADLs). The ADLs are frequently evaluated through self- or collateral report questionnaires, while performance-based measures are infrequently utilized, despite the decreased bias and increased accuracy and sensitivity associated with these instruments. This investigation compared ADLs between community-dwelling OAs with (n = 20) and without MCI (n = 30) using a self-report questionnaire (Older American Resources and Services Activities of Daily Living Scale; OARS), a collateral report questionnaire (OARS), and a performance-based measure (the Direct Assessment of Functional Status-Revised). Consistent with our hypothesis, OAs with MCI had decreased ADLs and IADLs on the performance-based measure compared to cognitively intact OAs, while there were no differences in ADLs or IADLs on self-report questionnaires or collateral report questionnaires. Our results suggest OAs with MCI have decreased ability to complete IADLs. However, this investigation suggests these deficits may not be detected by questionnaires and are more likely to be found with performance-based testing.
Yakoot, Mostafa; Salem, Amel; Helmy, Sherine
Background Mild cognitive impairment encompasses the clinical continuum between physiologic age-related cognitive changes and dementia. A variety of medications, including herbal preparations (in particular Ginkgo biloba and Panax ginseng), have been advocated as treatments for cognitive impairment in the elderly. In this study, we investigated the effect of an already marketed dietary supplement (Memo®) combining 750 mg of lyophilized royal jelly with standardized extracts of G. biloba 120 mg and P. ginseng 150 mg on Mini-Mental State Examination (MMSE) scores in patients with mild cognitive impairment. Methods Sixty-six subjects presenting with forgetfulness and satisfying the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) clinical criteria for mild cognitive impairment were randomly divided into an experimental group treated with one Memo capsule before breakfast daily for 4 weeks and a control group who took placebo. The mean change in MMSE score from baseline and reported adverse effects were compared between the two groups. Results The mean change in MMSE score in the group treated with Memo for 4 weeks was significantly greater than in the control group (+2.07 versus +0.13, respectively) by the Student’s t-test (t = 6.485, P < 0.0001). This was also true after adjusting for age as a covariate and educational level as a factor nested within the treatment groups in a general linear model (analysis of covariance, F = 9.675 [corrected model], P < 0.0001). Conclusion This combined triple formula may be beneficial in treating the cognitive decline that occurs during the aging process as well as in the early phases of pathologic cognitive impairment typical of insidious-onset vascular dementia and in the early stages of Alzheimer’s disease. Larger-sized studies with longer treatment durations are needed to confirm this. PMID:23950642
Pascoe, Michaela C; Linden, Thomas
Elderly stroke survivors are at risk of malnutrition and long-term cognitive impairment. Vitamin B-related metabolites, folate and methylmalonic acid, have been implicated in cognitive function. We conducted a study exploring the relationship between blood folate, methylmalonic acid and post-stroke cognitive impairment. This is a cross sectional study of elderly Swedish patients (n=149) 20 months post-stroke, assessed using the Mini Mental State Examination, serum blood levels of methylmalonic acid and red blood cell levels of folate. Linear modeling indicated that low levels of blood folate and elevated methylmalonic acid significantly contributed to cognitive impairment in stroke survivors. Half of the stroke survivors were shown to have folate deficiency at 20 months after stroke. Folate deficiency is common long term after stroke and both low folate and elevated methylmalonic acid appear to be associated with long term cognitive impairment, in elderly Swedish stroke survivors.
Smith, J Carson; Nielson, Kristy A; Antuono, Piero; Lyons, Jeri-Annette; Hanson, Ryan J; Butts, Alissa M; Hantke, Nathan C; Verber, Matthew D
Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer's disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD.
Smith, J. Carson; Nielson, Kristy A.; Antuono, Piero; Lyons, Jeri-Annette; Hanson, Ryan J.; Butts, Alissa M.; Hantke, Nathan C.; Verber, Matthew D.
Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer neuropathology, inefficient or ineffective neural processing, and increased risk for Alzheimer’s disease (AD). Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging. Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed a fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged .048 to .0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD. PMID:23803298
Whitson, Heather E.; Ansah, Deidra; Sanders, Linda L; Whitaker, Diane; Potter, Guy G.; Cousins, Scott W.; Steffens, David C.; Landerman, Lawrence R.; Pieper, Carl F.; Cohen, Harvey Jay
Background and Aims Comorbid cognitive impairment is common among visually impaired older adults. This study investigated whether baseline cognitive status predicts functional trajectories among older adults in low vision rehabilitation (LVR) for macular disease. Methods The Telephone Interview for Cognitive Status – modified (TICS-m) was administered to macular disease patients aged ≥ 65 years receiving outpatient LVR. Mixed models assessed the rate of change in instrumental activities of daily living and visual function measures over a mean follow-up of 115 days. Results Of 91 participants, 17 (18.7%) had cognitive impairment (TICS-m score ≤ 27) and 23 (25.3%) had marginal impairment (TICS-m scores 28 to 30). Controlling for age and gender, baseline cognitive status did not predict most functional outcomes. However, participants with marginal cognitive impairment experienced worse functional trajectories in ability to prepare meals (p=0.03).and activities that require distance vision (p = 0.05). Conclusion Patients with mild to moderate cognitive impairment should not be excluded from LVR, but programs should be prepared to detect and accommodate a range of cognitive ability. PMID:22526069
Background Detecting cognitive impairment in medical inpatients is important due to its association with adverse outcomes. Our aim was to study recognition of cognitive impairment and its association with mortality. Methods 200 inpatients aged over 60 years were recruited at the Department of General Internal Medicine at University Hospital MAS in Malmö, Sweden. The MMSE (Mini-Mental State Examination) and the CDT (Clock-Drawing Test) were performed and related to recognition rates by patients, staff physicians, nurses and informants. The impact of abnormal cognitive test results on mortality was studied using a multivariable Cox proportional hazards regression. Results 55 patients (28%) had no cognitive impairment while 68 patients (34%) had 1 abnormal test result (on MMSE or CDT) and 77 patients (39%) had 2 abnormal test results. Recognition by healthcare professionals was 12% in the group with 1 abnormal test and 44-64% in the group with 2 abnormal test results. In our model, cognitive impairment predicted 12-month mortality with a hazard ratio (95% CI) of 2.86 (1.28-6.39) for the group with 1 abnormal cognitive test and 3.39 (1.54-7.45) for the group with 2 abnormal test results. Conclusions Cognitive impairment is frequent in medical inpatients and associated with increased mortality. Recognition rates of cognitive impairment need to be improved in hospitals. PMID:22920412
Mohd Zulkifly, Mohd Faizal; Ghazali, Shazli Ezzat; Che Din, Normah; Singh, Devinder Kaur Ajit; Subramaniam, Ponnusamy
In this review, we aimed to identify the risk factors that may influence cognitive impairment among stroke survivors, namely, demographic, clinical, psychological, and physical determinants. A search from Medline, Scopus, and ISI Web of Science databases was conducted for papers published from year 2004 to 2015 related to risk factors of cognitive impairment among adult stroke survivors. A total of 1931 articles were retrieved, but only 27 articles met the criteria and were reviewed. In more than half of the articles it was found that demographical variables that include age, education level, and history of stroke were significant risk factors of cognitive impairment among stroke survivors. The review also indicated that diabetes mellitus, hypertension, types of stroke and affected region of brain, and stroke characteristics (e.g., size and location of infarctions) were clinical determinants that affected cognitive status. In addition, the presence of emotional disturbances mainly depressive symptoms showed significant effects on cognition. Independent relationships between cognition and functional impairment were also identified as determinants in a few studies. This review provided information on the possible risk factors of cognitive impairment in stroke survivors. This information may be beneficial in the prevention and management strategy of cognitive impairments among stroke survivors. PMID:27340686
Munger, Ronald G; Cutler, Adele; Quach, Anna; Bowles, Austin; Corcoran, Christopher; Tschanz, JoAnn T; Norton, Maria C; Welsh-Bohmer, Kathleen A
Background: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. Objective: We examined associations between Dietary Approaches to Stop Hypertension (DASH)– and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. Design: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. Results: The range of rank-order DASH and Mediterranean diet scores was 1661–25,596 and 2407–26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. Conclusions: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant
Yueh-Feng Lu, Yvonne; Bakas, Tamilyn; Haase, Joan E.
Purpose To describe and compare cost estimates for a pilot study of the Daily Enhancement of Meaningful Activity (DEMA) intervention for persons with mild cognitive impairment (PwMCI)-caregiver dyads. Background The increasing complexity of the health care system and rising health care costs, have forced nurse scientists to find ways to effectively improve health care quality and control cost, but no studies have examined costs for new programs that target PwMCI-caregiver dyads. Description of the project Pilot study data were used to develop a cost template and calculate the cost of implementing the DEMA. Outcomes Mean cost per dyad was estimated to be $1,327.97 in the clinical setting, compared with $1,069.06 if a telephone delivery mode had been used for four of the six face-to-face sessions. This difference was largely due to transportation-related expenses and staff cost. Implications DEMA should be evaluated further with larger and more diverse samples as a technology-delivered health promotion program that could reduce costs. PMID:23392066
Sun, Yuan; Yin, Xue Song; Guo, Hong; Han, Rong Kun; He, Rui Dong; Chi, Li Jun
Inflammatory mediators are closely associated with the pathogenesis of neurodegenerative changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Osteopontin (OPN) is a proinflammatory cytokine that has been shown to play an important role in various neuroinflammatory diseases. However, the function of OPN in AD and MCI progression is not well defined. Cerebrospinal fluid (CSF) and plasma samples were obtained from 35 AD patients, 31 MCI patients, and 20 other noninflammatory neurologic diseases (OND). Concentrations of OPN in the CSF and plasma were determined by enzyme-linked immunosorbent assay. During a 3-year clinical followup, 13 MCI patients converted to AD (MCI converters), and 18 were clinically stable (MCI nonconverters). CSF OPN concentrations were significantly increased in AD and MCI converters compared to OND, and increased levels of OPN in AD were associated with MMSE score; OPN protein levels both in the CSF and plasma of newly diagnosed AD patients were higher than that of chronical patients. In MCI converters individuals tested longitudinally, both plasma and CSF OPN concentrations were significantly elevated when they received a diagnosis of AD during followup. Further wide-scale studies are necessary to confirm these results and to shed light on the etiopathogenic role of osteopontin in AD. PMID:23576854
Gupta, Sunita; Parrino, Taryn E.; Knight, Alecia G.; Ebenezer, Philip J.; Weidner, Adam M.; LeVine, Harry; Keller, Jeffrey N.; Markesbery, William R.
Abstract This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47phox and the catalytic subunit gp91phox was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91phox, moderate levels of gp91phox also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD. Antioxid. Redox Signal. 12, 1371–1382. PMID:19929442
Krikorian, Robert; Shidler, Marcelle D; Dangelo, Krista; Couch, Sarah C; Benoit, Stephen C; Clegg, Deborah J
We randomly assigned 23 older adults with Mild Cognitive Impairment to either a hi