Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up.

Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.

Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women.

Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. MATERIALS AND METHODS: We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). RESULTS: After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p < .05 and F = 3.2670; p < .05, respectively). CONCLUSION: Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.

Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults.

BACKGROUND: There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis. OBJECTIVE: Serum vitamin D/bioactive (ionised) calcium/parathyroid hormone homeostasis was considered in the context of cognitive performance in healthy, middle-aged and older individuals. DESIGN: A cross-sectional sample of 179 participants between the ages of 47-84 years was recruited for this study (114 females, 65 males). Participants provided fasting blood samples for analysis of serum 25-hydroxyvitamin D levels, ionised calcium (iCa) and parathyroid hormone (PTH) and completed cognitive measures of verbal episodic learning and memory. RESULTS: Serum 25-hydroxyvitamin D concentrations were negatively associated (with and without covariates of age, gender, depression and NART scores, iCa, and PTH) with measures of verbal episodic learning and memory, in particular with trial 5 of the Rey Auditory Verbal Learning Test (RAVLT) and long-delay free recall on the RAVLT. CONCLUSION: Overall, the findings from this study suggest an association between higher vitamin D status and poorer performance on verbal episodic memory in middle-aged and older individuals with normal vitamin D-calcium-PTH homeostasis. Despite requiring replication in other participant samples, this is a potentially important finding as it indicates that it may not be beneficial from a cognitive perspective to provide vitamin D supplements in individuals with already adequate vitamin D status.

Good-quality diet in the early years may have a positive effect on academic achievement.

AIM: The aim of this study was to investigate the associations between early diet and academic performance during childhood. METHODS: Participants were from the Western Australian Pregnancy Cohort (Raine) Study (n = 2287). Frequency of consumption of food and beverages was collected at the one-, two- and three-year follow-ups, using a 24-hour food recall. Diet scores were developed from the number of eating occasions. The Western Australian Literacy and Numeracy Assessment (WALNA) data from grades five (age 10) and seven (age 12) were linked to the Raine study using The Western Australian Data Linkage System. The association between diet scores and WALNA scores was assessed using multivariate linear regression models. RESULTS: A higher (i.e. better quality) diet score at one year of age was associated with significantly higher scores in mathematics, reading, writing and spelling at both grades five and seven. Associations were observed between a higher diet score at two years and academic scores for mathematics, writing and spelling at grade seven. Higher dairy consumption at ages one, two and three, and higher fruit consumption at age one were associated with higher academic scores at all ages. CONCLUSION: Quality of early diet may be a predictor for later academic achievement.

Prospective associations between dietary patterns and cognitive performance during adolescence.

BACKGROUND: The aim of the study was to investigate prospective associations between dietary patterns and cognitive performance during adolescence. METHODS: Participants were sourced from the Western Australian Pregnancy Cohort (Raine) Study that includes 2868 children born between 1989 and 1992 in Perth, Western Australia. When the children were 17 years old (2006-2009), cognitive performance was assessed using a computerized cognitive battery of tests (CogState) that included six tasks. Using a food frequency questionnaire administered when the children were 14 years old (2003-2006), 'Healthy' and 'Western' dietary patterns were identified by factor analysis. Associations between dietary patterns at 14 years of age and cognitive performance at 17 years of age were assessed prospectively using multivariate regression models. RESULTS: Dietary and cognitive performance data were available for 602 participants. Following adjustment for the 'Healthy' dietary pattern, total energy intake, maternal education, family income, father's presence in the family, family functioning and gender, we found that a longer reaction time in the detection task (ß = .016; 95% CI: 0.004; 0.028; p = .009) and a higher number of total errors in the Groton Maze Learning Test - delayed recall task (ß = .060; 95% CI: 0.006; 0.114; p = .029) were significantly associated with higher scores on the 'Western' dietary pattern. The 'Western' dietary pattern was characterized by high intakes of take-away food, red and processed meat, soft drink, fried and refined food. We also found that within the dietary patterns, high intake of fried potato, crisps and red meat had negative associations, while increased fruit and leafy green vegetable intake had positive associations with some aspects of cognitive performance. CONCLUSION: Higher dietary intake of the 'Western' dietary pattern at age 14 is associated with diminished cognitive performance 3 years later, at 17 years.

Neuropsychological performance is positively associated with plasma albumin in healthy adults.

BACKGROUND: Albumin serves a range of physiological functions that are vital to overall brain and cognitive health. Indeed, associations between cognitive performance and albumin have been demonstrated in individuals with chronic liver or kidney disease and in patients with a high urinary excretion of albumin. However, an association of plasma albumin with cognitive performance has not been reported in otherwise healthy participants with clinically acceptable plasma albumin concentrations. METHOD: This study utilized a wide-ranging neuropsychological test battery to investigate the relationship between cognitive performance and plasma albumin homeostasis in 222 healthy participants (143 females) between the ages of 43 and 84 years (mean 65 years). RESULTS: Albumin both with and without the covariates of age, sex and acute-phase proteins was positively associated with enhanced performance on a range of neuropsychological domains including perceptual speed, Stroop and verbal ability. Albumin manifested generally positive but less robust associations with secondary and primary memory. CONCLUSION: The results indicate that there is a positive association between albumin and cognitive performance in physiologically healthy participants free of chronic renal or liver disease.

Lack of reliable evidence for a distinctive ε4-related cognitive phenotype that is independent from clinical diagnostic status: findings from the Australian Imaging, Biomarkers and Lifestyle Study.

Individuals who carry the apolipoprotein E ε4 polymorphism have an increased risk of late-onset Alzheimer's disease. However, because possession of the ε4 allele confers an increased risk for the diagnosis of dementia, it has proven problematic in older individuals to dissociate the influence of ε4 on cognitive capacity per se as distinct from its influence on clinical diagnostic status. We report a statistical approach that attempts to partial out the influence of diagnostic group membership (Alzheimer's disease, mild cognitive impairment, healthy control) from the influence of apolipoprotein ε4 genetic status on cognitive functioning. The cognitive phenotype hypothesis predicts that ε4-positive individuals will show cognitive deficits (relative to matched ε4-negative individuals) independent of the development of Alzheimer's disease. By contrast, the prodromal/preclinical Alzheimer's disease hypothesis proposes that the effect of apolipoprotein E status on cognitive performance is a function of the increased risk of dementia in individuals with the ε4 allele. We evaluated these hypotheses in the Australian Imaging, Biomarkers and Lifestyle cohort (n = 1112). We first determined whether previously reported findings concerning ε4 status and age-related neuropsychological performance could be explained by the inadvertent recruitment of people with mild cognitive impairment into the healthy control group. We then tested each diagnostic group in isolation to identify any neuropsychological patterns that may be attributed to the ε4 allele. Finally, as interactions between the ε4 allele and age have previously been reported in cognitive functioning within healthy elderly populations, we attempted to determine whether the inclusion of mild cognitively impaired individuals in the sample may drive this relationship. An extensive battery of standardized, well-validated neuropsychological tasks was administered to a final sample of 764 healthy control subjects, 131 individuals with mild cognitive impairment and 168 individuals with Alzheimer's disease. The effect of the ε4 allele on cognitive performance was assessed using a statistical mediation analysis and supplemented with Bayesian methods to address a number of the limitations associated with Fisherian/Neyman-Pearsonian significance testing. Our findings support the prodromal/preclinical Alzheimer's disease hypothesis and do not support the concept of a distinctive ε4-related cognitive phenotype.

Neuroticism (not depressive symptoms) predicts memory complaints in some community-dwelling older adults.

OBJECTIVES: To examine whether depressive symptoms are useful predictors of subjective memory complaints in community-dwelling older adults, beyond the predictive utility already provided by memory performance and characteristics of personality. DESIGN: Using hierarchical regression, we examined the relationship between depressive symptoms and subjective memory complaints, controlling for age, gender, education, memory performance, conscientiousness, and neuroticism. PARTICIPANTS: Community-dwelling older adults aged 66 to 90 years (N = 177) who responded to a newspaper advertisement for a memory study in Perth, Western Australia. MEASUREMENTS: The General Frequency of Forgetting scale (for memory complaints), Depression Anxiety Stress Scales (for depressive symptoms), NEO-Five Factor Inventory (for conscientiousness and neuroticism), and the Visual Reproduction and Logical Memory subtests from the Wechsler Memory Scale-4th Edition (for visual and verbal memory). RESULTS: The hierarchical regression analysis indicated that while depressive symptoms significantly predicted memory complaints after variance associated with age, gender, education, memory performance, and conscientiousness was partialled out, they accounted for almost none of the variance in complaints when neuroticism was partialled out. CONCLUSIONS: The well-established relationship between depression and memory complaints may exist in some community-dwelling older adult populations only on account of the manner in which both are associated with neuroticism.

Diet in the early years of life influences cognitive outcomes at 10 years: a prospective cohort study.

AIM: The aim of this study was to investigate the association between diet during the first 3 years of life and cognitive outcomes at 10 years of age. METHODS: The Raine Study is a longitudinal study of 2868 children and their families. Based on the foods reported to be eaten at age one, two and three, an Eating Assessment in Toddlers diet score was developed, consisting of seven components. Cognition was measured by the Peabody Picture Vocabulary Test-III (PPVT-III) and the Raven's Coloured Progressive Matrices at the 10-year follow-up. Associations were assessed in multivariate regression models. RESULTS: A higher Eating Assessment in Toddlers diet score at age one was associated with higher PPVT-III [ß = 0.12 (0.05, 0.19), p = 0.001] and Raven's Coloured Progressive Matrices scores [ß = 0.17 (0.02, 0.33), p = 0.025] at age ten after adjustments. Increased fruit consumption at age one was positively associated, while increased sweetened beverage consumption was negatively associated with cognitive development. Dairy consumption at ages two and three had positive associations with the PPVT-III and at age two with the Raven's Coloured Progressive Matrices. CONCLUSION: A better diet quality during the early years of life may have a positive effect on cognitive ability later in childhood.

Neurocognitive functioning in adolescents with eating disorders: a population-based study.

INTRODUCTION: Neurocognitive deficits have been identified in eating disorders, including anorexia nervosa and bulimia nervosa. However, current data do not allow for firm conclusions regarding the nature or extent of these deficits. The current study aimed to evaluate neurocognitive functioning in a population-based sample of adolescents with and without eating disorders. METHODS: Participants (N=669) were drawn from the Western Australian Pregnancy Cohort (Raine) Study. Cognitive testing was conducted using the computerised CogState assessment battery. Eating disorder symptoms were assessed using questions adapted from the Child Eating Disorder Examination and Eating Disorder Examination-Questionnaire. Adolescents who met full or partial criteria for a DSM-IV eating disorder (n=58) were compared to adolescents with no significant eating pathology (n=592). RESULTS: The eating disorder sample showed impaired performance on measures of executive functioning, including global processing and set shifting, but performed better than control participants on measures of visual attention and vigilance. CONCLUSIONS: This is the first study to evaluate neurocognitive functioning in a population-based sample of adolescents with eating disorders. Support is provided for weak central coherence and set-shifting difficulties early in the course of eating disorders. Research is needed to determine if these deficits precede and predict eating disorder onset.

Cognition and Cerebral Blood Flow After Extracranial Carotid Revascularization for Carotid Atherosclerosis: A Systematic Review.

PURPOSE: Extracranial atherosclerotic carotid stenosis is associated with inadequate cerebral blood flow (CBF) and cognitive dysfunction. The impact of extracranial carotid revascularization on cognition and how any cognitive change relates to changes in CBF are less clear. This review examines the effects of revascularization of extracranial carotid disease by carotid endarterectomy (CEA) or carotid stenting (CAS) on cognition, and how this relates to changes in CBF. METHODS: A systematic review of existing reports in the Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement recommendations. All original retrospective or prospective studies and clinical trials that compared pre- and postoperative cognitive function and CBF in patients with extracranial carotid stenosis who underwent CEA or CAS versus a control group, published between January 1985 and December 2022, were identified and considered eligible for inclusion in this study. FINDINGS: Seven studies (661 participants; 460 CEA or CAS) were identified. All were observational studies and of moderate to good methodologic quality. Six studies (619 participants; follow-up range 1 month to 2 years) demonstrated improvement in some cognitive domains following CEA or CAS, improvement in CBF following revascularization, and correlated some of these cognitive changes with changes in CBF. One study (42 participants; 3 months follow-up) found cognitive improvement following CEA, but found no improvement in CBF or any correlation between cognitive and CBF change. The literature however represented heterogenous study populations examining asymptomatic and/or symptomatic carotid stenosis, differing in treatment modality and criteria for control groups ranging from healthy volunteers to those with stenosis but not who underwent surgical revascularization, and finally, differing reporting methods. This heterogeneity precluded meta-analysis. IMPLICATIONS: Definitive conclusions are limited by variation in cognitive function assessment, timing of testing, and how these are correlated to CBF. However, research suggests a potential improvement in cognition which may be associated with improvement in CBF, particularly in those patients who have more significant CBF deficit at baseline. Further studies are required to better understand this association and provide a clearer picture of the cognitive effects of carotid revascularization.

Age and premorbid intelligence suppress complaint-performance congruency in raw score measures of memory.

BACKGROUND: We aimed to examine the role of age and premorbid intelligence (IQ) in suppressing the relationship between subjective memory complaints (SMCs) and raw score memory performance. METHODS: We used a community sample of older adults aged 66-90 years (N = 121) to test whether the inclusion of age and a premorbid IQ measure in multiple regression analyses increased semipartial correlations of raw score memory performance in predicting SMCs. Rank contrast correlations were also carried out to observe how age and premorbid IQ are related to complaint-performance congruency. Measures utilized in the study included the Memory Functioning Questionnaire (for SMCs), Visual Reproduction and Logical Memory Subtests (memory performance), and the National Adult Reading Test (premorbid IQ). RESULTS: Inclusion of age and premorbid IQ in the multiple regression analyses increased semipartial correlations for all raw score measures of memory. Both age and premorbid IQ were significantly related to complaint-performance congruency, whereby older participants and those with lower premorbid IQ scores rated their memory abilities more leniently than younger and higher premorbid IQ participants. CONCLUSION: The results suggest differences in age and premorbid IQ play a small role in suppressing the relationship between SMCs and memory performance when utilizing raw score measures of memory.

Efficacy of probucol on cognitive function in Alzheimer's disease: study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA study).

INTRODUCTION: Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid beta (Aß) in the peripheral circulation is causally related to the development of Alzheimer's disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aß compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aß moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aß secretion, concomitant with maintaining blood-brain-barrier function, suppressing neurovascular inflammation and supporting cognitive function. This protocol details the probucol in Alzheimer's study, a drug intervention trial investigating if probucol has potential to attenuate cognitive decline, delay brain atrophy and reduce cerebral amyloid burden in patients with mild-to-moderate AD. METHODS AND ANALYSIS: The study is a phase II, randomised, placebo-controlled, double-blind single-site clinical trial held in Perth, Australia. The target sample is 314 participants with mild-to-moderate AD. Participants will be recruited and randomised (1:1) to a 104-week intervention consisting of placebo induction for 2 weeks followed by 102 weeks of probucol (Lorelco) or placebo. The primary outcome is changed in cognitive performance determined via the Alzheimer's Disease Assessment Scales-Cognitive Subscale test between baseline and 104 weeks. Secondary outcomes measures will be the change in brain structure and function, cerebral amyloid load, quality of life, and the safety and tolerability of Lorelco, after a 104week intervention. ETHICS AND DISSEMINATION: The study has been approved by the Bellberry Limited Human Research Ethics Committee (approval number: HREC2019-11-1063; Version 4, 6 October 2021). Informed consent will be obtained from participants prior to any study procedures being performed. The investigator group will disseminate study findings through peer-reviewed publications, key conferences and local stakeholder events. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000726853).

Awareness of cognitive deficits in older adults with cognitive-impairment-no-dementia (CIND): comparison with informant report.

Impaired awareness of cognitive deficits is a common symptom of dementia, but its prognostic importance in people with cognitive impairment-no dementia (CIND) is uncertain. In this study, we examined whether community volunteers with CIND and reduced awareness had worse cognitive performance and cognitive decline over 18 months than CIND participants with intact awareness or healthy controls. We recruited 92 participants with CIND and 91 healthy controls with their respective informants. We used discrepancy scores (informant minus participant) on the Anosognosia Questionnaire for Dementia and Dysexecutive Questionnaire to ascertain participants' awareness of their cognitive performance. The main cognitive outcome variable was the Alzheimer Disease Assessment Scale: Cognitive Section. Bivariate correlations showed no relationship between the awareness measures and cognitive performance or decline. Overall, CIND participants' ratings of cognitive deficits correlated significantly with their Alzheimer Disease Assessment Scale: Cognitive Section score after 18-months (for Anosognosia Questionnaire for Dementia, r=0.45, P <0.001) and showed a stronger relationship with cognitive performance than informant ratings. These results indicate that reduced awareness of deficit may be uncommon in community volunteer samples with CIND. In addition, self-report of cognitive complaints may be at least as useful as informant report when screening community-dwelling older adults at risk of cognitive decline and dementia.

The amnesic syndrome of primary Whipple disease of the brain.

OBJECTIVE: To describe a case of primary Whipple disease (WD) of the brain, which may manifest as an amnesic syndrome. MATERIALS AND METHODS: A 46-year-old woman developed primary WD of the brain. The onset was characterized by a short-term amnesic syndrome for several months before the onset of generalized tonic-clonic seizures. Her amnesia was stable throughout her illness. RESULTS: Our patient had impairment of verbal and visual memory tasks with reduced learning. Her amnesic syndrome was secondary to asymmetric bilateral hippocampal atrophy with gliosis involving the mesial temporal structures-all secondary to primary WD of the brain. CONCLUSIONS: WD may present as an amnesic syndrome and needs to be thought of as a treatable cause of cognitive dysfunction in young adults.

Effect of hot versus cold climates on power output, muscle activation, and perceived fatigue during a dynamic 100-km cycling trial.

The purpose of this study was to examine the influence of environmental temperature on power output, muscle activation, body temperature, and perceived physical strain during a dynamic self-paced 100-km cycling trial. Nine endurance-trained male cyclists (mean + or - s: age 31 + or - 6 years; VO(2max) 62.1 + or - 8.5 ml x kg(-1) x min(-1)) completed two 100-km experimental trials, interspersed with five 1-km and four 4-km high-intensity epochs, in hot (34 degrees C) and cold (10 degrees C) environments. Measurements consisted of power output, rectal and skin temperature, muscle activation of vastus lateralis, biceps femoris and soleus, ratings of perceived exertion, thermal sensation and pain intensity in the quadriceps. Power output and muscle activation of the biceps femoris and soleus were lower in the hot trial (22 km; P < 0.05) prior to significant (P < 0.05) differences in rectal temperature [38.8 degrees C (cold) vs. 39.1 degrees C (hot)] at 42 km. Muscle activation of the vastus lateralis, biceps femoris, and soleus was significantly (P < 0.001) correlated with power output and thermal sensation (r > 0.68) but not with perceived pain or exertion. Thus, a hyperthermic-induced anticipatory reduction of muscle activation may have occurred during the hot exercise trials only. Fatigue and pacing during prolonged dynamic exercise in the cold appears to be influenced by factors dissociated from hyperthermic-induced stress.

The relationship between memory complaints, perceived quality of life and mental health in apolipoprotein Eepsilon4 carriers and non-carriers.

Apolipoprotein E epsilon4 (APOE-epsilon4) is a major genetic risk factor for Alzheimer's disease. In this study, we addressed the question of whether possession of the APOE-epsilon4 allele results in adverse effects on perceived health-related quality of life (HRQL) and on symptoms of depression and anxiety in people with subjective memory complaints (SMC). 138 healthy, community-dwelling elderly volunteers, aged 52 to 85, were assessed for HRQL, depression, and anxiety. The participants were classified as i) APOE-epsilon4 carriers or ii) non-carriers with a) SMC or b) without memory complaints. The possible interactions of APOE genotype, gender, and SMC on HRQL, depression, and anxiety were investigated statistically. SMC was significantly associated with poorer outcomes on measures of depression, trait anxiety, and mental health. APOE-epsilon4 carriers did not significantly differ from non-carriers on HRQL, depression, and anxiety. However, significant interaction was found between APOE-epsilon4 genotype and SMC on depression. These findings are important from a health perspective and suggest that memory complaints are associated with markers of mental health and quality of life that are independent of possession of the APOE-epsilon4 allele, despite the importance of this polymorphism in the risk of AD and other health problems.

Olfactory dysfunction is associated with subjective memory complaints in community-dwelling elderly individuals.

Olfactory dysfunction has been reported in clinical and preclinical phases of Alzheimer's disease. Subjective memory complaints have been proposed as a potential early indicator for increased risk of Alzheimer's disease, but have also been associated with depression, personality characteristics, and health problems. In this study, we aimed to determine which of these putative markers can predict memory complaints in community-dwelling elderly individuals, focusing on olfactory symptoms. A cohort of 144 elderly volunteers (42 males and 102 females), aged 50 to 86, was recruited from an ongoing longitudinal study. Participants were assessed for olfactory capacities (threshold, discrimination, and identification), subjective memory complaints, depression, and cognitive functions. Subjective memory complaints were significantly associated with olfactory discrimination and identification but not with threshold. Olfactory functions and depressive symptoms were both significantly associated with subjective memory complaints. In addition, memory complainers were significantly worse than non-complainers with respect to olfactory discrimination, identification, and overall olfactory functioning. The findings suggest that olfactory capacity may be a potentially significant biomarker for identifying community-dwelling elderly with memory complaints who are at increased risk for age-related cognitive decline and Alzheimer's disease.

Fluoro-2-deoxy-D-glucose (FDG)-PET in APOEepsilon4 carriers in the Australian population.

Apolipoprotein E-epsilon4 (APOEepsilon4) has been associated with increased risk of developing Alzheimer's disease (AD) and regional cerebral glucose hypometabolism, as measured by fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). We report here preliminary data from studies that aim to determine whether cerebral glucose hypometabolism is observed in APOEepsilon4 positive, cognitively intact individuals between the ages of 50 and 80, and whether there is an additional impact of subjective memory complainer (SMC) status on glucose metabolism determined by NeuroStat analysis. FDG-PET was conducted in 30 community dwelling, APOE-epsilon4 carriers without clinical evidence of dementia and objective cognitive impairment as assessed using a neuropsychological battery. Neurological soft-signs (NSS) were also assessed. Glucose hypometabolism was demonstrated in the anterior and posterior cingulate cortex and in the temporal association cortices in APOEepsilon4 carriers compared to the normative NeuroStat database. This pattern was particularly evident in APOEepsilon4 heterozygous individuals. SMC showed hypometabolism in the aforementioned brain regions, whereas non-SMC showed no significant pattern of glucose hypometabolism. FDG-PET with NeuroStat analysis showed that APOEepsilon4 carriers have mild glucose hypometabolism in areas associated with AD. SMC may be associated with AD-related differences in regional cerebral glucose metabolism. These findings are currently being investigated in a larger group of APOEepsilon4 carriers.

Luteinizing hormone levels are positively correlated with plasma amyloid-beta protein levels in elderly men.

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.