Mild cognitive impairment.
Mild cognitive impairment (MCI) is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer’s disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.
Srp Arh Celok Lek. 2009 Jul-Aug;137(7-8):434-9
Memory profiling in mild cognitive impairment: can we determine risk for Alzheimer’s disease?
Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer’s disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that ‘memory profiling’ of individuals with MCI may help identify which individuals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non-preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow-up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.
J Neuropsychol. 2008 Sep;2(Pt 2):361-72
Cognitive modifications associated with tobacco smoking.
INTRODUCTION: Tobacco is an important source of somatic diseases and causes high mortality. It is associated with cognitive disorders which tend to maintain addictive mechanisms. In the short term, the nicotine contained in tobacco enhances attention and memory. METHOD: To realize this review, we made a research, we made a research on Medline, Embase, PsycInfo, Google Scholar using the single or combined key-words “tobacco,” “nicotine,” “addiction,” “dependence,” “cognitive disorders,” “executive function,” “memory,” “attention,” “neuropsychological.” We selected English or French articles from 1987 to 2008 by privileging controlled studies. RESULTS: This effect can be observed in smokers (with or without withdrawal symptoms), non-smokers and in patients suffering from cognitive disorders. In the long term, tobacco accelerates dementia processes. It is associated with an increased risk of cognitive deterioration. This deterioration concerns mainly memory and processing speed. These results were reported in prospective studies. They contradict early reports, that suggested smoking could actually be protective against certain central neural system disorders. These early results relayed on case-control studies, which were certainly biased by a “healthy survival effect.” Further studies are required to evaluate nicotine’s long term effect and its potential efficacy in treating and preventing cognitive disorders or dementia.
Presse Med. 2009 Sep;38(9):1241-52
Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.
AIMS: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. METHODS: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. RESULTS: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. CONCLUSIONS: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.
Alcohol Alcohol. 2009 Jul-Aug;44(4):372-81
Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial.
CONTEXT: Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking. OBJECTIVE: To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING: Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS: We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION: Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE: Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS: In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly. CONCLUSIONS: In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.
JAMA. 2008 Sep 3;300(9):1027-37
Preserve brain function...through physical exercise?
Over the last few years, there has been an increasing interest in the relationship between brain function and physical exercise. Preliminary evidence from observational and interventional studies in humans suggests a positive and robust effect of chronic aerobic exercise on several brain functions across the entire lifespan. Physical activity and exercise might also serve to reduce the risk of age-associated neurological disorders such as Alzheimer’s and Parkinson’s diseases. The mechanisms underlying these beneficial effects remain poorly understood. More scientific work is needed before disseminating more specific recommendations to the general population.
Rev Med Liege. 2008 May-Jun;63(5-6):293-8
Alzheimer’s disease, cerebrovascular dysfunction and the benefits of exercise: from vessels to neurons.
Exercise training promotes extensive cardiovascular changes and adaptive mechanisms in both the peripheral and cerebral vasculature, such as improved organ blood flow, induction of antioxidant pathways, and enhanced angiogenesis and vascular regeneration. Clinical studies have demonstrated a reduction of morbidity and mortality from cardiovascular disease among exercising individuals. However, evidence from recent large clinical trials also suggests a substantial reduction of dementia risk - particularly regarding Alzheimer’s disease (AD) - with regular exercise. Enhanced neurogenesis and improved synaptic plasticity have been implicated in this beneficial effect. However, recent research has revealed that vascular and specifically endothelial dysfunction is essentially involved in the disease process and profoundly aggravates underlying neurodegeneration. Moreover, vascular risk factors (VRFs) are probably determinants of incidence and course of AD. In this review, we emphasize the interconnection between AD and VRFs and the impact of cerebrovascular and endothelial dysfunction on AD pathophysiology. Furthermore, we describe the molecular mechanisms of the beneficial effects of exercise on the vasculature such as activation of the vascular nitric oxide (NO)/endothelial NO synthase (eNOS) pathway, upregulation of antioxidant enzymes, and angiogenesis. Finally, recent prospective clinical studies dealing with the effect of exercise on the risk of incident AD are briefly reviewed. We conclude that, next to upholding neuronal plasticity, regular exercise may counteract AD pathophysiology by building a vascular reserve.
Exp Gerontol. 2008 Jun;43(6):499-504
Biological mechanisms of physical activity in preventing cognitive decline.
In order to guarantee better conditions for competition, the nervous system has developed not only mechanisms controlling muscle effectors, but also retrograde systems that, starting from peripheral structures, may influence brain functions. Under such perspective, physical activity could play an important role in influencing cognitive brain functions including learning and memory. The results of epidemiological studies (cross-sectional, prospective and retrospective) support a positive relationship between cognition and physical activities. Recent meta-analysis confirmed a significant effect of exercise on cognitive functions. However, the biological mechanisms that underlie such beneficial effects are still to be completely elucidated. They include supramolecular mechanisms (e.g. neurogenesis, synaptogenesis, and angiogenesis) which, in turn, are controlled by molecular mechanisms, such as BDNF, IGF-1, hormone and second messengers.
Cell Mol Neurobiol. 2010 May;30(4):493-503
BDNF is a novel marker of cognitive function in ageing women: the DR’s EXTRA Study.
Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating brain plasticity. While low circulating levels of BDNF have been suggested to predispose to Alzheimer’s disease, very little data are available on its association with cognitive function in general population. We evaluated the association between plasma BDNF levels and cognition in a representative population sample of ageing men and women. The subjects (n=1389) were participants of the Dose-Responses to Exercise Training (DR’s EXTRA) Study and represent a random sample of Eastern Finnish people (684 men and 705 women), 57-79 years of age at baseline of the study. Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological test battery. Women had a higher mean (+/-SEM) plasma BDNF level than men (1721+/-55vs. 1495+/-54pg/ml, P<0.001). In women, 1 SD decrease in BDNF increased the risk for a low score in Naming Test by 53% (95% CI 1.21-1.92, P<0.001), in Mini-Mental State Examination by 63% (95% CI 1.21-2.20, P=0.001), in Word List Memory by 56% (95% CI 1.08-2.26, P=0.019), in Word List Recall by 50% (95% CI 1.10-2.05, P=0.010), in Word List Saving by 49% (95% CI 1.12-1.99, P=0.007), and in Word List Recognition by 64% (95% CI 1.19-2.25, P=0.002). Data were adjusted for age, education, depression, impaired glucose metabolism, cardiovascular disease, antihypertensive medication, lipid lowering medication, use of sex hormones, smoking, alcohol consumption, storing time of plasma in the freezer and platelet count. BDNF was not associated with cognition in men. Present data suggest that plasma BDNF is a biomarker of impaired memory and general cognitive function in ageing women.
Neurobiol Learn Mem. 2008 Nov;90(4):596-603