Whole genome sequencing in transposition of the great arteries and associations with clinically relevant heart, brain and laterality genes.

BACKGROUND: The most common cyanotic congenital heart disease (CHD) requiring management as a neonate is transposition of great arteries (TGA). Clinically, up to 50% of TGA patients develop some form of neurodevelopmental disability (NDD), thought to have a significant genetic component. A "ciliopathy" and links with laterality disorders have been proposed. This first report of whole genome sequencing in TGA, sought to identify clinically relevant variants contributing to heart, brain and laterality defects. METHODS: Initial whole genome sequencing analyses on 100 TGA patients focussed on established disease genes related to CHD (n = 107), NDD (n = 659) and heterotaxy (n = 74). Single variant as well as copy number variant analyses were conducted. Variant pathogenicity was assessed using the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines. RESULTS: Fifty-five putatively damaging variants were identified in established disease genes associated with CHD, NDD and heterotaxy; however, no clinically relevant variants could be attributed to disease. Notably, case-control analyses identified significantly more predicted-damaging, silent and total variants in TGA cases than healthy controls in established CHD genes (P < .001), NDD genes (P < .001) as well as across the three gene panels (P < .001). CONCLUSION: We present compelling evidence that the majority of TGA is not caused by monogenic rare variants and is most likely oligogenic and/or polygenic in nature, highlighting the complex genetic architecture and multifactorial influences on this CHD sub-type and its long-term sequelae. Assessment of variant burden in key heart, brain and/or laterality genes may be required to unravel the genetic contributions to TGA and related disabilities.

Lifetime cigarette smoking is associated with striatal volume measures.

Nicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers' brains have smaller cortical grey matter volumes and/or lower densities compared with non-smokers'. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community-based sample of 'young-old' individuals. Brain volumes were measured using a semi-automated method in 315 participants aged 64-70 years who were selected from a larger randomly sampled cohort and who consented to a magnetic resonance imaging scan. Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age, sex, intracranial and total brain volumes and general physical and mental health measures. Greater lifetime use of cigarettes (measured in pack-years) was associated with smaller left nucleus accumbens area volume (P = 0.018) and larger left putamen volume (P = 0.025). Greater putaminal volume was also associated with a lower age at smoking initiation (P = 0.004). In this generally healthy cohort, lifetime use of cigarettes is significantly associated with striatal volume measures. These changes could indicate predisposing factors for nicotine addiction, or an effect of chronic nicotine exposure or a combination of both.

Effect of model choice in genetic association studies: DRD4 exon III VNTR and cigarette use in young adults.

A major concern with the vast literature associating the highly polymorphic 48 bp VNTR in exon III of the human dopamine receptor D4 gene (DRD4) with various behavioral phenotypes is the lack of concordance between studies. Part of the problem arises from the absence of a universally accepted scheme for pooling the large number of low frequency genotypes into appropriate categories. Here, we investigated the effect of different pooling strategies and genetic models on the reported association between DRD4-exIII-VNTR polymorphism and cigarette smoking. Genotyping was performed on a large randomly selected community-based sample of 2,274 individuals aged 20-24 years. Participants were grouped into sub-samples based on their genotypes to test specific genetic models. Multiple regression analyses were used to assess the relationship between DRD4-exIII-VNTR genotype and cigarette smoking measures while controlling for confounders. While smoking status and age at start of smoking were not associated with the genotype, a significantly (P = 0.006) higher rate of cigarette consumption was observed among carriers of the 7-repeat (7r) allele. Thus, 7r carriers were not more likely to be smokers but if they did smoke they consumed significantly more cigarettes per day than 4r carriers. Unlike previous studies this association was observed only when comparing carriers of the 7r with the 4r but not the other repeat alleles. Our study demonstrates the need for caution when grouping functionally different DRD4-exIII-VNTR alleles in association studies. It particularly highlights the requirement for better functional characterization of the DRD4-exIII-VNTR alleles for interpreting results from association studies.

Ecological and health risk assessment of trace metals in water collected from Haripur gas blowout area of Bangladesh.

The study aims to assess the trace metals and physicochemical properties of water in the adjacent to the Sylhet gas blowout area. Trace metals were analyzed using atomic absorption spectrophotometer, whereas physicochemical parameters were evaluated in-situ state using portable instruments and also in the laboratory. Trace metals Pb, Cd, and Ni were found in the water samples higher than the acceptable limit by WHO standards, whereas the concentration of Cu and Zn were within acceptable limit, respectively. The correlation coefficient matrix and factor loading analysis spectacle that the interrelationship among the physicochemical parameters, trace elements, as well as other ions are moderate to strongly corellated which reflecting the homogeneous source of origin. According to contamination factor, Nemerow multi-factor index, pollution load index, and also, potential ecological risk index, the water of the region is quite polluted in case of Pb, Cd, and Ni but unpolluted for Cu and Zn. The water quality index indicates that treatment of water is required before using it for domestic purposes. The health quotient and hazard index results are less than standard value 1 suggesting that there is no noncarcinogenic risk in the area. The carcinogenic analysis shows that the lifetime incremental cancer risk mean value of Cd and Ni are fairly insignificant and Pb is more significant for children to cause health problem. The ILCR value of Cd and Ni are insignificant whereas Pb is significant to pose health risk for adults. Physicochemical parameters revealed that the water was slightly acidic and soft in nature implying to avoid the water from this area for drinking purposes. At the end, it can be concluded that this study will be useful for the residence as well as the policymaker to take the protective surveillance measures around the areas.

Epidemiologic investigation and targeted vaccination initiative in response to an outbreak of meningococcal disease among illicit drug users in Brooklyn, New York.

BACKGROUND: An outbreak of serogroup C meningococcal disease that involved illicit drug users and their contacts occurred in Brooklyn, New York, during 2005 and 2006. METHODS: The objectives of this study were to identify the population at risk for meningococcal disease, describe efforts to interrupt disease transmission, and assess the impact of a vaccine initiative. Descriptive and molecular epidemiological analysis was used to define the extent of the outbreak and the common risk factors among outbreak-related cases. A vaccine initiative that used community-based service providers was targeted to illicit drug users and their close contacts. The vaccine initiative was assessed through cessation of outbreak-related cases and the reduction in carriage rate. RESULTS: The investigation identified 23 outbreak-related cases of serogroup C meningococcal disease; 17 isolates were indistinguishable and 4 isolates were closely related according to pulsed-field gel electrophoresis. Two additional culture-negative cases had epidemiological links to laboratory-confirmed cases. The median age of patients with outbreak-related cases was 41 years, and 19 (83%) of 23 patients reported an association with illicit drug use. There were 7 outbreak-related deaths. Vaccination was administered to 2763 persons at 29 community locations, including methadone treatment centers, syringe-exchange programs, and soup kitchens. Three additional cases of meningococcal disease due to strains with the same pulsed-field gel electrophoresis pattern were identified after the vaccination initiative. CONCLUSIONS: Community-based outbreaks of meningococcal disease are difficult to control, and the decision to vaccinate is not straightforward. Current national guidelines for implementing a vaccination campaign are not strict criteria and cannot be expected to accommodate the myriad of factors that occur in community-based invasive meningococcal disease outbreaks, such as the inability to enumerate the population at risk.

Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease.

The identification of novel genetic variants contributing to the widespread in the age of onset (AOO) of Alzheimer's disease (AD) could aid in the prognosis and/or development of new therapeutic strategies focused on early interventions. We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia, Colombia. These individuals belong to the world largest multigenerational and extended pedigree segregating AD as a consequence of a dominant fully penetrant mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the late 1970s. To shed light on the genetic underpinning that could explain the large spread of the age of onset (AOO) of AD, 64 single nucleotide polymorphisms (SNP) associated with neuroanatomical, cardiovascular, and cognitive measures in AD were genotyped. Standard quality control and filtering procedures were applied, and single- and multi-locus linear mixed-effects models were used to identify AOO-associated SNPs. A full two-locus interaction model was fitted to define how identified SNPs interact to modulate AOO. We identified two key epistatic interactions between the APOE*E2 allele and SNPs ASTN2-rs7852878 and SNTG1-rs16914781 that delay AOO by up to ~ 8 years (95% CI 3.2-12.7, P = 1.83 × 10-3) and ~ 7.6 years (95% CI 3.3-11.8, P = 8.69 × 10-4), respectively, and validated our previous finding indicating that APOE*E2 delays AOO of AD in PSEN1 E280 mutation carriers. This new evidence involving APOE*E2 as an AOO delayer could be used for developing precision medicine approaches and predictive genomics models to potentially determine AOO in individuals genetically predisposed to AD.

Gene expression analysis in post-embryonic pericardial cells of Drosophila.

Increasing evidence suggests conservation of cardiovascular molecules between vertebrates and invertebrates. Vertebrate Rudhira, an evolutionary conserved WD40 protein is expressed during primitive erythropoiesis, neoangiogenesis and tumors. We report here the expression profile of the Drosophila ortholog of Rudhira (DRudh) in the fly life cycle. DRudh is expressed specifically in all post-embryonic pericardial cells (PCs) and garland cells (GCs). This is the first report of a cytoplasmic marker highly specific to post-embryonic PCs. Embryonic PCs belong to three distinct genetic classes based on Odd-skipped (Odd), Even-skipped (Eve) and Tinman (Tin) expression. To identify which among these three classes of PCs expresses DRudh in post-embryonic stages, we analyzed expression of embryonic PC markers in the post-embryonic stages. Unlike in the embryo all larval PCs show an identical gene expression profile. While Odd and Eve expression is mutually exclusive in the embryonic PCs, these two markers are co-expressed in larval PCs but show a distinct subcellular localization. Tin is not expressed in any post-embryonic PC. Additionally larval PCs also express the GATA factor, Serpent (Srp) and the extracellular matrix protein, Pericardin (Prc). While PC number is known to decrease post-embryogenesis, which of the Odd or Eve lineage embryonic PCs persists is not known. Co-expression of the two distinct lineage markers only in post-embryonic stages indicates a complex temporal regulation of gene expression in PCs.

Late Onset Alzheimer's Disease Risk Variants in Cognitive Decline: The PATH Through Life Study.

Recent genome wide association studies have identified a number of single nucleotide polymorphisms associated with late onset Alzheimer's disease (LOAD). We examined the associations of 24 LOAD risk loci, individually and collectively as a genetic risk score, with cognitive function. We used data from 1,626 non-demented older Australians of European ancestry who were examined up to four times over 12 years on tests assessing episodic memory, working memory, vocabulary, and information processing speed. Linear mixed models were generated to examine associations between genetic factors and cognitive performance. Twelve SNPs were significantly associated with baseline cognitive performance (ABCA7, MS4A4E, SORL1), linear rate of change (APOE, ABCA7, INPP5D, ZCWPW1, CELF1), or quadratic rate of change (APOE, CLU, EPHA1, HLA-DRB5, INPP5D, FERMT2). In addition, a weighted genetic risk score was associated with linear rate of change in episodic memory and information processing speed. Our results suggest that a minority of AD related SNPs may be associated with non-clinical cognitive decline. Further research is required to verify these results and to examine the effect of preclinical AD in genetic association studies of cognitive decline. The identification of LOAD risk loci associated with non-clinical cognitive performance may help in screening for individuals at greater risk of cognitive decline.

Regional Brain Volumes and ADHD Symptoms in Middle-Aged Adults: The PATH Through Life Study.

OBJECTIVE: We investigated whether volumetric differences in ADHD-associated brain regions are related to current symptoms of inattention and hyperactivity in healthy middle-aged adults and whether co-occurring anxiety/depression symptoms moderate these relationships. METHOD: ADHD Self-Report Scale and Brief Patient Health Questionnaire were used to assess current symptoms of inattention, hyperactivity, anxiety, and depression in a population-based sample ( n = 269). Brain volumes, measured using a semi-automated method, were analyzed using multiple regression and structural equation modeling to evaluate brain volume-inattention/hyperactivity symptom relationships for selected regions. RESULTS: Volumes of the left nucleus accumbens and a region overlapping the dorsolateral prefrontal cortex were positively associated with inattention symptoms. Left hippocampal volume was negatively associated with hyperactivity symptoms. The brain volume-inattention/hyperactivity symptom associations were stronger when anxiety/depression symptoms were controlled for. CONCLUSION: Inattention and hyperactivity symptoms in middle-aged adults are associated with different brain regions and co-occurring anxiety/depression symptoms moderate these brain-behavior relationships.

Association of genetic risk factors with cognitive decline: the PATH through life project.

We examined the association of 28 single nucleotide polymorphisms (SNPs), previously associated with dementia or cognitive performance, with tests assessing episodic memory, working memory, vocabulary, and perceptual speed in 1689 nondemented older Australians of European ancestry. In addition to testing each variant individually, we assessed the collective association of the 12-risk SNPs for late-onset Alzheimer's disease using weighted and unweighted genetic risk scores. Significant associations with cognitive performance were observed for APOE ε4 allele, ABCA7-rs3764650, CR1-rs3818361, MS4A4E-rs6109332, BDNF-rs6265, COMT-rs4680, CTNNBL-rs6125962, FRMD4A-rs17314229, FRMD4A-rs17314229, intergenic SNP chrX-rs12007229, PDE7A-rs10808746, SORL1-rs668387, and ZNF224-rs3746319. In addition, the weighted genetic risk score was associated with worse performance on episodic memory. The identification of genetic risk factors, that act individually or collectively, may help in screening for people with elevated risk of cognitive decline and for understanding the biological pathways that underlie cognitive decline.

Retrospective assessment of childhood ADHD symptoms for diagnosis in adults: validity of a short 8-item version of the Wender-Utah Rating Scale.

The Wender-Utah Rating Scale (WURS) is a widely used self-report instrument for retrospective assessment of childhood ADHD. However, many WURS items are not specific to ADHD. Here, we investigated the effect of excluding these items on the performance of the WURS in predicting adult ADHD based on previous diagnosis and current clinically significant symptoms. The study was conducted on a sample of adults (n = 1014; 48 % male) participating in a family-based investigation of ADHD. Participants completed the 61-item WURS questionnaire and the 66-item Conners Adult ADHD Rating Scale. Receiver operating characteristic (ROC) curves were used to compare the performance of the eight-item WURS (WURS-8) and the longer WURS-25 in predicting previous ADHD diagnosis and current clinically significant ADHD symptoms. WURS-8 and WURS-25 have approximately the same power to predict adult ADHD, based on either previous diagnosis or current symptoms (area under the ROC curves >0.8). WURS-8 performs at least as well as the longer WURS-25 in predicting adult ADHD. This 8-item questionnaire is thus a valid instrument and is especially useful for screening for ADHD in large epidemiological samples.

Associations between corpus callosum size and ADHD symptoms in older adults: The PATH through life study.

Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed deviations of the corpus callosum in children and adolescents. However, little is known about the link between callosal morphology and symptoms of inattention or hyperactivity in adulthood, especially later in life. Here, we investigated in a large population-based sample of 280 adults (150 males, 130 females) in their late sixties and early seventies whether ADHD symptoms correlate with callosal thickness. In addition, we tested for significant sex interactions, which were followed by correlation analyses stratified by sex. Within males, there were significant negative correlations with respect to inattention and hyperactivity in various callosal regions, including the anterior third, anterior and posterior midbody, isthmus, and splenium. A thinner corpus callosum may be associated with fewer fibers or less myelination of fibers. Thus, the observed negative correlations suggest impaired inter-hemispheric communication channels necessary to sustain motor control and attention, which may contribute to symptoms of hyperactivity, impulsivity and/or inattention. Interestingly, within females, callosal thickness was positively related to hyperactivity in a small area within the rostral body, suggesting a sexually dimorphic neurobiology of ADHD symptoms. Altogether, the present results may reflect a lasting relationship between callosal morphology and ADHD symptoms throughout life.

Preventing skin cancer: findings of the Task Force on Community Preventive Services On reducing Exposure to Ultraviolet Light.

Rates of skin cancer, the most common cancer in the United States, are increasing. The most preventable risk factor for skin cancer is unprotected ultraviolet (UV) exposure. Seeking to identify effective approaches to reducing the incidence of skin cancer by improving individual and community efforts to reduce unprotected UV exposure, the Task Force on Community Preventive Services conducted systematic reviews of community interventions to reduce exposure to ultraviolet light and increase protective behaviors. The Task Force found sufficient evidence to recommend two interventions that are based on improvements in sun protective or "covering-up" behavior (wearing protective clothing including long-sleeved clothing or hats): educational and policy approaches in two settings--primary schools and recreational or tourism sites. They found insufficient evidence to determine the effectiveness of a range of other population-based interventions and recommended additional research in these areas: educational and policy approaches in child care centers, secondary schools and colleges, recreational or tourism sites for children, and workplaces; interventions conducted in health-care settings and targeted to both providers and children's parents or caregivers; media campaigns alone; and community wide multicomponent interventions. This report also presents additional information regarding the recommended community interventions, briefly describes how the reviews were conducted, provides resources for further information, and provides information that can help in applying the interventions locally. The U.S. Preventive Services Task Force conducted a systematic review of counseling by primary care clinicians to prevent skin cancer (CDC. Counseling to prevent skin cancer: recommendation and rationale of the U.S. Preventive Services Task Force. MMWR 2003;52[No. RR-15]:13-17), which is also included in this issue, the first jointly released findings from the Task Force on Community Preventive Services and the U.S. Preventive Services Task Force.

Interactive effect of APOE genotype and blood pressure on cognitive decline: the PATH through life study.

The apolipoprotein E (APOE) *ε4 allele and hypertension are two of the most prevalent risk factors for cognitive decline in later life. Here we investigate whether cognitive decline is affected by interaction between these two risk factors. Specifically, we examine whether APOE*ε4 moderates the association between high blood pressure and cognition in later life. Cognitive function was assessed at three time points over a period of 8 years in 1,474 cognitively normal, community-dwelling adults aged 60-64 years at baseline. Blood pressure and APOE genotype were assessed at baseline. Blood pressure was measured categorically as 'Hypertension' and continuously as 'Mean Arterial Pressure' (MAP). Multilevel models were used to investigate main and interactive effects of APOE genotype and both hypertension and MAP on the rate of change of episodic memory, working memory, verbal ability, perceptual speed, and global cognition. The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition. However, its inclusion in the model did not increase the amount of outcome variation explained beyond that already explained by the effect of time. In contrast, the APOE-MAP interaction had no effect on the rate of decline in any of these domains of cognitive performance. These results provide tentative evidence that APOE genotype moderates the association between high blood pressure and cognitive decline in later life.

ADHD symptoms and cognitive abilities in the midlife cohort of the PATH through life study.

OBJECTIVE: ADHD is a lifelong condition, but it remains understudied in older adults. We examined the effects of ADHD-related inattention and hyperactivity symptoms on cognitive abilities in middle-age adults. METHOD: ADHD symptoms and cognitive abilities were accessed in a population-based sample (N = 2,091). Multiple regression analyses evaluated the effect of dimensional and categorical measures of ADHD on performance in cognitive tests. RESULTS: ADHD symptoms are negatively associated with measures of reaction time, processing speed, task-switching, mental flexibility, and an aggregate measure of cognition. Inattention and hyperactive symptoms have reciprocal effects on performance in some cognitive tasks. Significant subclinical effects are present. CONCLUSION: Our demonstration that cognitive effects of ADHD symptoms are present in the middle-age population provides the impetus to investigate whether these effects contribute to cognitive decline in late age and whether identification and treatment of ADHD symptoms in middle age might be effective in reducing late-age cognitive decline.

Interventions to prevent skin cancer by reducing exposure to ultraviolet radiation: a systematic review.

The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

Attention Deficit/Hyperactivity Disorder symptoms and cognitive abilities in the late-life cohort of the PATH through life study.

Attention Deficit/Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder that has not been well studied in older adults. In this study we examined relationships between ADHD symptoms and cognitive ability and compared them between middle-age (MA; 48-52 years) and older-age (OA; 68-74 years) adults sampled from the same population. ADHD, mood disorder symptoms and cognitive abilities were assessed in a large population-based sample (n = 3443; 50% male). We measured current ADHD symptoms using the adult ADHD Self-Report Scale (ASRS), which we found to have the same underlying structure in both cohorts. Older adults reported significantly lower levels of ADHD symptoms and 2.2% of the OA cohort scored equal or above the ASRS cut-off score of 14 (which has been previously associated with ADHD diagnosis) compared with 6.2% of MA adults. Symptom levels were not significantly different between males and females. Using multi-group structural equation modelling we compared ADHD symptom-cognitive performance relationships between the two age groups. Generally higher ADHD symptoms were associated with poorer cognitive performance in the MA cohort. However, higher levels of inattention symptoms were associated with better verbal ability in both cohorts. Surprisingly, greater hyperactivity was associated with better task-switching abilities in older adults. In the OA cohort ADHD symptom-cognition relationships are indirect, mediated largely through the strong association between depression symptoms and cognition. Our results suggest that ADHD symptoms decrease with age and that their relationships with co-occurring mood disorders and cognitive performance also change. Although symptoms of depression are lower in older adults, they are much stronger predictors of cognitive performance and likely mediate the effect of ADHD symptoms on cognition in this age group. These results highlight the need for age-appropriate diagnosis and treatment of comorbid ADHD and mood disorders.

Cognitive ability, intraindividual variability, and common genetic variants of catechol-O-methyltransferase and brain-derived neurotrophic factor: a longitudinal study in a population-based sample of older adults.

Genetic differences play a significant role in generating individual differences in cognitive abilities. Studies have linked common polymorphisms (valine to methionine substitution; VAL/MET) in the catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) to cognitive differences between individuals. However, not all studies support these associations and hence, the impact of these polymorphisms on cognition is unclear. Here, we investigated the effect of COMT VAL158MET and BDNF VAL66MET polymorphisms and their interaction on cognitive performance measured longitudinally over 8 years in a population-based sample of older adults (60-64 years at baseline; n = 400). We used multilevel models to examine differences between individuals with different genotypes in performance on psychometric tests while controlling for age, sex, and education. We observed significant main and interaction effects of COMT and BDNF genotypes on reaction time (RT) and intraindividual variability in RT (IIV-RT). Subjects with at least one copy of the COMT*MET allele (which is associated with higher prefrontal dopamine) had significantly faster RT (both simple and choice RT) and less IIV-RT in both tasks than those without the COMT*MET allele when they also carried one or more BDNF*MET alleles (which is associated with lower activity-dependent BDNF secretion). However, RT and IIV-RT did not differ significantly between the COMT genotypes in the absence of the BDNF*MET allele. These polymorphisms had no significant effect on within person change in RT or IIV-RT. Our findings indicate that the interaction between common variants of COMT and BDNF explain individual differences in RT and IIV-RT but do not explain age-related decline in these abilities.

A population-based study of attention deficit/hyperactivity disorder symptoms and associated impairment in middle-aged adults.

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent childhood psychiatric condition. It frequently persists into adulthood and can have serious health and other adverse consequences. The majority of previous adult ADHD studies have focused on young adults so that relatively little is known about ADHD symptoms and their effects in mid and late life. In addition, effects of subclinical levels of attention deficit and hyperactivity have not been studied in detail. In this study we investigated ADHD symptoms and related impairment in a large population-based sample of middle-aged Australian adults (n = 2091; 47% male). Applying the WHO adult ADHD Self Report Screener (ASRS) we observed that 6.2% of participants had scores that were previously associated with ADHD diagnosis. No significant gender difference in the distribution of ASRS scores was observed. Multiple regression analyses indicated strong positive correlations between symptoms of ADHD and depression/anxiety and significant negative associations (p<0.01) with employment, financial stress, relationship quality, health and well-being measures in this age group. Importantly, associations were highly significant even when few ADHD symptoms were reported. Compared to the hyperactivity component, the inattention trait was particularly strongly associated and remained significant after controlling for depression/anxiety symptoms. Our study confirms previous findings and significantly adds to existing literature especially for an age-group that has not been well-studied. Our results suggest that ADHD symptoms continue to be associated with ill-health and functional impairment in mid-life and are, therefore, likely to be a major, previously unrecognized source of late-life morbidity with associated social and economic costs. Thus, there is a compelling need for better understanding and development of age-appropriate approaches to the diagnosis and treatment of ADHD in mid- to late-life.