Jonathan K. Foster

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. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12605000136606.

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimers disease (AD). To complicate matters, possession of one or more apolipoprotein E ɛ4 (APOE ɛ4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and Aβ clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE ɛ4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE ɛ4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.

Social cognition in frontotemporal dementia and Huntington's disease

Frontotemporal dementia (FTD) and Huntingtons disease (HD) are degenerative disorders, with predominant involvement, respectively of frontal neocortex and striatum. Both conditions give rise to altered social conduct and breakdown in interpersonal relationships, although the factors underlying these changes remain poorly defined. The study used tests of theory of mind (interpretation of cartoons and stories and judgement of preference based on eye gaze) to explore the ability of patients with FTD and HD to interpret social situations and ascribe mental states to others. Performance in the FTD group was severely impaired on all tasks, regardless of whether the test condition required attribution of a mental state. The HD group showed a milder impairment in cartoon and story interpretation, and normal preference judgements. Qualitative differences in performance were demonstrated between groups. FTD patients made more concrete, literal interpretations, whereas HD patients were more likely to misconstrue situations. The findings are interpreted as demonstrating impaired theory of mind in FTD, as one component of widespread executive deficits. In HD the evidence does not suggest a fundamental loss of theory of mind, but rather a tendency to draw faulty inferences from social situations. It is concluded that social breakdown in FTD and HD may have a different underlying basis and that the frontal neocortex and striatum have distinct contributions to social behaviour.

The role of nutrition in children's neurocognitive development, from pregnancy through childhood

This review examines the current evidence for a possible connection between nutritional intake (including micronutrients and whole diet) and neurocognitive development in childhood. Earlier studies which have investigated the association between nutrition and cognitive development have focused on individual micronutrients, including omega-3 fatty acids, vitamin B12, folic acid, choline, iron, iodine, and zinc, and single aspects of diet. The research evidence from observational studies suggests that micronutrients may play an important role in the cognitive development of children. However, the results of intervention trials utilizing single micronutrients are inconclusive. More generally, there is evidence that malnutrition can impair cognitive development, whilst breastfeeding appears to be beneficial for cognition. Eating breakfast is also beneficial for cognition. In contrast, there is currently inconclusive evidence regarding the association between obesity and cognition. Since individuals consume combinations of foods, more recently researchers have become interested in the cognitive impact of diet as a composite measure. Only a few studies to date have investigated the associations between dietary patterns and cognitive development. In future research, more well designed intervention trials are needed, with special consideration given to the interactive effects of nutrients.

Patterns of Autobiographical Memory Loss in Medial-Temporal Lobe Amnesic Patients

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of ones personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.

Glucose facilitation of cognitive performance in healthy young adults: examination of the influence of fast-duration, time of day and pre-consumption plasma glucose levels.

Abstract.Rationale: Previous investigations have demonstrated increased performance after the administration of a glucose-load on certain aspects of cognitive functioning in healthy young adults. Generally these studies have used a procedure where participants were tested in the morning after an overnight fast. Objective: The aim of the present study was, for the first time, to investigate the glucose cognitive facilitation effect under more natural testing times and with shorter duration of the previous fast. Methods: Measures of verbal and non-verbal memory performance were compared under different fasting intervals (2-h fast versus overnight fast), times (morning versus afternoon) and glycaemic conditions (glucose versus aspartame drinks) in healthy young participants. Results: There was a significant glucose facilitation effect on long-term verbal memory performance. In addition, glucose significantly enhanced long-term spatial memory performance. The effect of glucose was essentially equivalent whether it was given after an overnight fast or a 2-h fast following breakfast or lunch. There was no effect of drink and time of day on working memory performance. Conclusions: The results of this study further support the hypothesis that glucose administration can enhance certain aspects of memory performance in healthy young adults. More significantly, the findings indicate that this cognitive facilitation effect persists under more naturalistic conditions of glucose administration and is not restricted to long fast durations or morning administration.

Cognitive impairment, physical disability and depressive symptoms in older diabetic patients: the Fremantle Cognition in diabetes study

OBJECTIVE To determine whether the prevalence of dementia, depression and/or disability in older diabetic subjects warrants an active screening approach by diabetes health care workers. PATIENTS AND METHODS The initial 223 members of a cohort of 529 eligible diabetic subjects, aged 70 years or over, were screened for cognitive impairment (using the Mini-Mental State Examination (MMSE) and Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE)), physical impairments and depressive symptoms. RESULTS Virtually all subjects were community-dwelling (99%) and mobile (86%) and relatively few had moderate or severe deficits in activities of daily living (ADL) (17.5%). The prevalences of cognitive impairment and probable dementia estimated from the screening tests were high (range 10.8-17.5%) compared with population studies. Any deficit with ADL was reported by 53% of the subjects and common problems included urinary and faecal incontinence. Scores consistent with clinical depression were reported by 14.2% of the sample but 50.2% of the remainder reported one or more depressive symptoms below the cut-off point for clinical depression. Only 36% of the study subjects were free of deficits in any domain. CONCLUSIONS Community-living older diabetic subjects have high rates of cognitive impairment, deficits in physical function and depressive symptomatology suggesting that screening programs for functional impairments and depression may be beneficial in health care systems that manage older diabetic patients.

Bone mineral density, adiposity, and cognitive functions

Cognitive decline and dementia due to Alzheimers disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34–87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms.

Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging

Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimers disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Abeta as an AD biomarker and its relationship with Abeta load and to determine the effect of different assay methods on the interpretation of Abeta levels. Plasma Abeta1-40, Abeta1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Abeta levels were compared to Abeta load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Abeta1-42 and Abeta1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Abeta load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Abeta isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Abeta has diagnostic value in a panel of biomarkers.

The effect of retrograde and anterograde glucose administration on memory performance in healthy young adults

Memory for a list of 20 words can be enhanced by preceding learning by consumption of 25 g of glucose, compared with consumption of an equally sweet aspartame solution (Psychopharmacology 137 (1998) 259; Psychopharmacology 157 (2001) 46). However, using this anterograde administration procedure, it is impossible to separate whether glucose affects encoding, consolidation, or retrieval. The present placebo-controlled, double-blind study investigated the effect of anterograde and retrograde administration on memory performance in healthy young participants. In order to evaluate whether post-acquisition administration of glucose can improve memory performance and to compare possible differences in the size of the effect, participants were administered 25 g of glucose immediately before or immediately after presentation of a word list. Moreover, in order to investigate whether the effect of glucose administration on memory performance is time-dependent, a third group received 25 g of glucose 15 min before learning the word list. Word- list recall was tested 30 min and 24 h after word list presentation. Measures of spatial memory performance and working memory were also evaluated. The results of this study showed that both pre- and post-acquisition oral glucose administration (25 g) can improve memory performance. However, as the time interval between anterograde glucose administration and memory encoding increased, the glucose memory facilitation effect decreased. This study provides evidence that glucose enhances memory performance in healthy young people even when it is given after learning has taken place, and that this effect is observed at least up to 24 h after glucose administration. Moreover, it provides evidence that the effect of glucose on memory performance may be time-dependent, as the enhancement of retention was decreased when the administration-learning interval was increased.