Premotor-Motor Interhemispheric Inhibition Is Released during Movement Initiation in Older but Not Young Adults

Neural interactions between contralateral motor regions are thought to be instrumental in the successful preparation, and execution, of volitional movements. Here we investigated whether healthy ageing is associated with a change in functional connectivity, as indicated by the ability to modulate interhemispheric interactions during movement preparation in a manner that assists rapid movement responses. Thirteen young (mean age 22.2 years) and thirteen older (68.5 years) adults rapidly abducted their left index finger as soon as possible in response to a visual imperative signal, presented 500 ms after a visual warning signal.Interactions between left dorsal premotor cortex (LPMd) and right primary motor cortex (RM1) and between left primary motor cortex (LM1) and RM1 were investigated at six time points between the warning signal and the volitional response using paired-pulse transcranial magnetic stimulation. Relative to the inhibitory interactions measured at rest, both young and older adults released LM1-RM1 inhibition beginning 250 ms after the warning signal, with no significant differences between groups. LPMd-RM1 interactions became facilitatory (from the onset of the imperative signal onwards) in the older, but not the young, group. Regression analyses revealed that for the older adults, modulation of LPMd-RM1 interactions early in the preparation period was associated with faster responses, suggesting that specifically timed modulation of these pathways may be a compensatory mechanism to offset, at least in part, slowing of motor responses. The results suggest a greater reliance on premotor regions during the preparation of simple motor actions with advancing age.     

Kinematic Analysis of the Neck and Upper Extremities During Walking in Healthy Young Adults

The objective of this paper is to quantify the local stabilities of the neck and upper extremities (right/left shoulders and right/left elbows), and investigate differences between linear and nonlinear measurements of the associated joint motions and differences in the local stability between the upper and lower extremities. This attempt involves the calculation of a nonlinear parameter, Lyapunov Exponent (LE), and a linear parameter, Range of Motion (ROM), during treadmill walking in conjunction with a large population of healthy subjects. Joint motions of subjects were captured using a three-dimensional motion-capture system. Then mathematical chaos theory and the Rosenstein algorithm were employed to calculate LE of joints as the extent of logarithmic divergence between the neighboring state-space trajectories of flexion-extension angles. LEs computed over twenty males and twenty females were 0.037±0.023 for the neck, 0.043±0.021 for the right shoulder, 0.045±0.030 for the left shoulder, 0.032±0.021 for the right elbow, and 0.034±0.026 for the left elbow. Although statistically significant difference in the ROM was observed between all pairs of the neck and upper extremity joints, differences in the LE between all pairs of the joints as well as between males and females were not statistically significant. Between the upper and lower extremities, LEs of the neck, shoulder, and elbow were significantly smaller than those of the hip (∼0.064) and the knee (∼0.062). These results indicate that a statistical difference in the local stability between the upper extremity joints is not significant. However, the different result between the ROM and LE gives a strong rationale for applying both linear and nonlinear tools together to the evaluation of joint movement. The LEs of the joints calculated from a large population of healthy subjects could provide normative values for the associated joints and can be used to evaluate the recovery progress of patients with joint related diseases.     

Biological Markers of Auditory Gap Detection in Young,Middle-Aged,and Older Adults

The capability of processing rapid fluctuations in the temporal envelope of sound declines with age and this contributes to older adults'' difficulties in understanding speech. Although, changes in central auditory processing during aging have been proposed as cause for communication deficits, an open question remains which stage of processing is mostly affected by age related changes. We investigated auditory temporal resolution in young, middle-aged, and older listeners with neuromagnetic evoked responses to gap stimuli with different leading marker and gap durations. Signal components specific for processing the physical details of sound stimuli as well as the auditory objects as a whole were derived from the evoked activity and served as biological markers for temporal processing at different cortical levels. Early oscillatory 40-Hz responses were elicited by the onsets of leading and lagging markers and indicated central registration of the gap with similar amplitude in all three age groups. High-gamma responses were predominantly related to the duration of no-gap stimuli or to the duration of gaps when present, and decreased in amplitude and phase locking with increasing age. Correspondingly, low-frequency activity around 200 ms and later was reduced in middle aged and older participants. High-gamma band, and long-latency low-frequency responses were interpreted as reflecting higher order processes related to the grouping of sound items into auditory objects and updating of memory for these objects. The observed effects indicate that age-related changes in auditory acuity have more to do with higher-order brain functions than previously thought.     

Identifying Stride-To-Stride Control Strategies in Human Treadmill Walking

Variability is ubiquitous in human movement, arising from internal and external noise, inherent biological redundancy, and from the neurophysiological control actions that help regulate movement fluctuations. Increased walking variability can lead to increased energetic cost and/or increased fall risk. Conversely, biological noise may be beneficial, even necessary, to enhance motor performance. Indeed, encouraging more variability actually facilitates greater improvements in some forms of locomotor rehabilitation. Thus, it is critical to identify the fundamental principles humans use to regulate stride-to-stride fluctuations in walking. This study sought to determine how humans regulate stride-to-stride fluctuations in stepping movements during treadmill walking. We developed computational models based on pre-defined goal functions to compare if subjects, from each stride to the next, tried to maintain the same speed as the treadmill, or instead stay in the same position on the treadmill. Both strategies predicted average behaviors empirically indistinguishable from each other and from that of humans. These strategies, however, predicted very different stride-to-stride fluctuation dynamics. Comparisons to experimental data showed that human stepping movements were generally well-predicted by the speed-control model, but not by the position-control model. Human subjects also exhibited no indications they corrected deviations in absolute position only intermittently: i.e., closer to the boundaries of the treadmill. Thus, humans clearly do not adopt a control strategy whose primary goal is to maintain some constant absolute position on the treadmill. Instead, humans appear to regulate their stepping movements in a way most consistent with a strategy whose primary goal is to try to maintain the same speed as the treadmill at each consecutive stride. These findings have important implications both for understanding how biological systems regulate walking in general and for being able to harness these mechanisms to develop more effective rehabilitation interventions to improve locomotor performance.     

Correlation of Six-Minute Walking Performance with Quality of Life is Domain- and Gender-Specific in Healthy Older Adults

We analyzed the relationship between performance on the 6-min walk test (6MWT) and health-related quality of life (HRQoL) in older subjects. Our secondary aim was to determine the distance to be completed on the 6MWT for the subject to achieve a score of 50 on the Short Form (36) Health Survey (SF-36). Associations were tested using linear correlation and multivariate linear regression. Participants were 130 healthy older individuals. The predictive performance of the 6MWT based on an SF-36 score of 50 was assessed using a receiver operating characteristic curve and its area under curve (AUC). Associations were observed between physical functioning, role-emotional, social functioning, vitality, general health score, and 6MWT performance in women, after adjusting for confounding variables (coefficients: 0.57, 0.38, 0.40, and 0.46, respectively; p < 0.05). No association was found for men. The distance for the 6MWT to predict an SF-36 score of 50 was 481 m for men in the physical functioning (AUC: 0.79) and role-physical (AUC: 0.84) domains, and 420 m for women in role-emotional (AUC: 0.75), role-physical (AUC: 0.80), and general health (AUC: 0.80) domains. Our results indicate that superior 6MWT performance may be associated with better HRQoL in several domains in only healthy older women. No association between 6MWT performance and role-emotional, mental health, or vitality domains was found. We suggest that a score of 50 is represented by a 6MWT distance of 481 m for men and 420 m for women, at least in the role-physical domain.     

Facebook Use Predicts Declines in Subjective Well-Being in Young Adults

Over 500 million people interact daily with Facebook. Yet, whether Facebook use influences subjective well-being over time is unknown. We addressed this issue using experience-sampling, the most reliable method for measuring in-vivo behavior and psychological experience. We text-messaged people five times per day for two-weeks to examine how Facebook use influences the two components of subjective well-being: how people feel moment-to-moment and how satisfied they are with their lives. Our results indicate that Facebook use predicts negative shifts on both of these variables over time. The more people used Facebook at one time point, the worse they felt the next time we text-messaged them; the more they used Facebook over two-weeks, the more their life satisfaction levels declined over time. Interacting with other people “directly” did not predict these negative outcomes. They were also not moderated by the size of people''s Facebook networks, their perceived supportiveness, motivation for using Facebook, gender, loneliness, self-esteem, or depression. On the surface, Facebook provides an invaluable resource for fulfilling the basic human need for social connection. Rather than enhancing well-being, however, these findings suggest that Facebook may undermine it.     

Oxygen Therapy Use in Older Adults with Chronic Obstructive Pulmonary Disease

Rationale

Oxygen therapy improves survival and function in severely hypoxemic chronic obstructive pulmonary disease (COPD) patients based on two landmark studies conducted over 40 years ago. We hypothesize that oxygen users in the current era may be very different. We examined trends and subject characteristics associated with oxygen therapy use from 2001–2010 in the United States.

Methods

We examined Medicare beneficiaries with COPD who received oxygen from 2001 to 2010. COPD subjects were identified by: 1) ≥2 outpatient visits >30 days apart within one year with an encounter diagnosis of COPD; or 2) an acute care hospitalization with COPD as the primary or secondary discharge diagnosis. Oxygen therapy and sustained oxygen therapy were defined as ≥1 and ≥11 claims for oxygen, respectively, in the durable medical equipment file in a calendar year. Primary outcome measures were factors associated with oxygen therapy and sustained oxygen therapy over the study period.

Results

Oxygen therapy increased from 33.7% in 2001 to 40.5% in 2010 (p-value of trend <0.001). Sustained oxygen therapy use increased from 19.5% in 2001, peaked in 2008 to 26.9% and declined to 18.5% in 2010. The majority of subjects receiving oxygen therapy and sustained oxygen therapy were female. Besides gender, factors associated with any oxygen use or sustained oxygen therapy were non-Hispanic white race, low socioeconomic status and ≥2 comorbidities.

Conclusions

Any oxygen use among fee-for service Medicare beneficiaries with COPD is high. Current users of oxygen are older females with multiple comorbidities. Decline in sustained oxygen therapy use after 2008 may be related to reimbursement policy change.     

Physical Demand but Not Dexterity Is Associated with Motor Flexibility during Rapid Reaching in Healthy Young Adults

Healthy humans are able to place light and heavy objects in small and large target locations with remarkable accuracy. Here we examine how dexterity demand and physical demand affect flexibility in joint coordination and end-effector kinematics when healthy young adults perform an upper extremity reaching task. We manipulated dexterity demand by changing target size and physical demand by increasing external resistance to reaching. Uncontrolled manifold analysis was used to decompose variability in joint coordination patterns into variability stabilizing the end-effector and variability de-stabilizing the end-effector during reaching. Our results demonstrate a proportional increase in stabilizing and de-stabilizing variability without a change in the ratio of the two variability components as physical demands increase. We interpret this finding in the context of previous studies showing that sensorimotor noise increases with increasing physical demands. We propose that the larger de-stabilizing variability as a function of physical demand originated from larger sensorimotor noise in the neuromuscular system. The larger stabilizing variability with larger physical demands is a strategy employed by the neuromuscular system to counter the de-stabilizing variability so that performance stability is maintained. Our findings have practical implications for improving the effectiveness of movement therapy in a wide range of patient groups, maintaining upper extremity function in old adults, and for maximizing athletic performance.     

Control of Fingertip Forces in Young and Older Adults Pressing against Fixed Low- and High-Friction Surfaces

Mobile computing devices (e.g., smartphones and tablets) that have low-friction surfaces require well-directed fingertip forces of sufficient and precise magnitudes for proper use. Although general impairments in manual dexterity are well-documented in older adults, it is unclear how these sensorimotor impairments influence the ability of older adults to dexterously manipulate fixed, low-friction surfaces in particular. 21 young and 18 older (65+ yrs) adults produced maximal voluntary contractions (MVCs) and steady submaximal forces (2.5 and 10% MVC) with the fingertip of the index finger. A Teflon covered custom-molded splint was placed on the fingertip. A three-axis force sensor was covered with either Teflon or sandpaper to create low- and high-friction surfaces, respectively. Maximal downward forces (F_z) were similar (p = .135) for young and older adults, and decreased by 15% (p<.001) while pressing on Teflon compared to sandpaper. Fluctuations in F_z during the submaximal force-matching tasks were 2.45× greater (p<.001) for older adults than in young adults, and reached a maximum when older adults pressed against the Teflon surface while receiving visual feedback. These age-associated changes in motor performance are explained, in part, by altered muscle activity from three hand muscles and out-of-plane forces. Quantifying the ability to produce steady fingertip forces against low-friction surfaces may be a better indicator of impairment and disability than the current practice of evaluating maximal forces with pinch meters. These age-associated impairments in dexterity while interacting with low-friction surfaces may limit the use of the current generation of computing interfaces by older adults.     

Natural Experience Modulates the Processing of Older Adult Faces in Young Adults and 3-Year-Old Children

Just like other face dimensions, age influences the way faces are processed by adults as well as by children. However, it remains unclear under what conditions exactly such influence occurs at both ages, in that there is some mixed evidence concerning the presence of a systematic processing advantage for peer faces (own-age bias) across the lifespan. Inconsistency in the results may stem from the fact that the individual’s face representation adapts to represent the most predominant age traits of the faces present in the environment, which is reflective of the individual’s specific living conditions and social experience. In the current study we investigated the processing of younger and older adult faces in two groups of adults (Experiment 1) and two groups of 3-year-old children (Experiment 2) who accumulated different amounts of experience with elderly people. Contact with elderly adults influenced the extent to which both adult and child participants showed greater discrimination abilities and stronger sensitivity to configural/featural cues in younger versus older adult faces, as measured by the size of the inversion effect. In children, the size of the inversion effect for older adult faces was also significantly correlated with the amount of contact with elderly people. These results show that, in both adults and children, visual experience with older adult faces can tune perceptual processing strategies to the point of abolishing the discrimination disadvantage that participants typically manifest for those faces in comparison to younger adult faces.     

Anodal tDCS over the Motor Cortex on Prepared and Unprepared Responses in Young Adults

Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been proposed as a possible therapeutic rehabilitation technique for motor impairment. However, despite extensive investigation into the effects of anodal tDCS on motor output, there is little information on how anodal tDCS affects response processes. In this study, we used a cued go/nogo task with both directional and non-directional cues to assess the effects of anodal tDCS over the dominant (left) primary motor cortex on prepared and unprepared motor responses. Three experiments explored whether the effectiveness of tDCS varied with timing between stimulation and test. Healthy, right-handed young adults participated in a double-blind randomised controlled design with crossover of anodal tDCS and sham stimulation. In Experiment 1, twenty-four healthy young adults received anodal tDCS over dominant M1 at least 40 mins before task performance. In Experiment 2, eight participants received anodal tDCS directly before task performance. In Experiment 3, twenty participants received anodal tDCS during task performance. In all three experiments, participants responded faster to directional compared to non-directional cues and with their right hand. However, anodal tDCS had no effect on go/nogo task performance at any stimulation – test interval. Bayesian analysis confirmed that anodal stimulation had no effect on response speed. We conclude that anodal tDCS over M1 does not improve response speed of prepared or unprepared responses of young adults in a go/nogo task.     

Strokes in Young Adults

Occlusion of the internal carotid or middle cerebral artery was seen in 44 young adults of both sexes from a rural population in Ceylon over a period of four years. None had hypertension, diabetes, prediabetes, or hypercholesterolaemia. There were 19 men with internal carotid occlusions, most being due to atherosclerotic thrombosis. The high incidence of atherosclerosis in these patients on a marginal diet remains an enigma, and we suggest that carbohydrate-induced hyperlipidaemia might be an important aetiological factor. There were 13 men with middle cerebral occlusions, the aetiology of which remains obscure. Occult embolism or atherothrombosis are suggested as possible causative factors. Of the 12 women five had middle cerebral artery occlusions in the last trimester of pregnancy and two had internal carotid artery occlusions in the puerperium. The pattern of ischaemic strokes in women aged 15-45 was similar to that observed in Western countries, though our patients differed ethnologically and in dietary habits.     

Step-to-Step Variability in Treadmill Walking: Influence of Rhythmic Auditory Cueing

While walking, human beings continuously adjust step length (SpL), step time (SpT), step speed (SpS = SpL/SpT) and step width (SpW) by integrating both feedforward and feedback mechanisms. These motor control processes result in correlations of gait parameters between consecutive strides (statistical persistence). Constraining gait with a speed cue (treadmill) and/or a rhythmic auditory cue (metronome), modifies the statistical persistence to anti-persistence. The objective was to analyze whether the combined effect of treadmill and rhythmic auditory cueing (RAC) modified not only statistical persistence, but also fluctuation magnitude (standard deviation, SD), and stationarity of SpL, SpT, SpS and SpW. Twenty healthy subjects performed 6×5 min. walking tests at various imposed speeds on a treadmill instrumented with foot-pressure sensors. Freely-chosen walking cadences were assessed during the first three trials, and then imposed accordingly in the last trials with a metronome. Fluctuation magnitude (SD) of SpT, SpL, SpS and SpW was assessed, as well as NonStationarity Index (NSI), which estimates the dispersion of local means in the times series (SD of 20 local means over 10 steps). No effect of RAC on fluctuation magnitude (SD) was observed. SpW was not modified by RAC, what is likely the evidence that lateral foot placement is separately regulated. Stationarity (NSI) was modified by RAC in the same manner as persistent pattern: Treadmill induced low NSI in the time series of SpS, and high NSI in SpT and SpL. On the contrary, SpT, SpL and SpS exhibited low NSI under RAC condition. We used relatively short sample of consecutive strides (100) as compared to the usual number of strides required to analyze fluctuation dynamics (200 to 1000 strides). Therefore, the responsiveness of stationarity measure (NSI) to cued walking opens the perspective to perform short walking tests that would be adapted to patients with a reduced gait perimeter.     

Cognitive and Typing Outcomes Measured Simultaneously with Slow Treadmill Walking or Sitting: Implications for Treadmill Desks

Purpose

This study compared cognitive (attention, learning, and memory) and typing outcomes during slow treadmill walking or sitting. Seventy-five healthy individuals were randomly assigned to a treadmill walking group (n=37; 23 female) or sitting group (n=38; 17 female).

Methods

The treadmill walking group completed a series of tests while walking at 1.5 mph. The sitting group performed the same tests while sitting at a standard desk. Tests performed by both groups included: the Rey Auditory Verbal Learning Test and a modified version of the Paced Auditory Serial Attention Test. In addition, typing performance was evaluated.

Results

Participants in the treadmill walking group performed worse on the Rey Auditory Verbal Learning Test for total learning than the sitting group; the main effect was significant (F(1,73)=4.75, p=0.03, η _p ²=0.06); however, short- and long-delay recall performance did not differ between groups (p>0.05). For the Paced Auditory Serial Attention Test, total number of correct responses was lower in the treadmill walking group relative to the sitting group; the main effect was significant (F(1,73)=4.97, p=0.03, η _p ²=0.06). The performance of both groups followed the same learning slope (Group x Trial interactions were not significant) for the Rey Auditory Verbal Learning Test and Paced Auditory Serial Attention Test. Individuals in the treadmill walking group performed significantly worse for all measures of typing (p<0.05).

Conclusion

Walking on a treadmill desk may result in a modest difference in total learning and typing outcomes relative to sitting, but those declines may not outweigh the benefit of the physical activity gains from walking on a treadmill.     

The Ethics of Deprescribing in Older Adults

Deprescribing is the term used to describe the process of withdrawal of an inappropriate medication supervised by a clinician. This article presents a discussion of how the Four Principles of biomedical ethics (beneficence, non-maleficence, autonomy, and justice) that may guide medical practitioners’ prescribing practices apply to deprescribing medications in older adults. The view of deprescribing as an act creates stronger moral duties than if viewed as an omission. This may explain the fear of negative outcomes which has been reported by prescribers as a barrier to deprescribing. Respecting the autonomy of older adults is complex as they may not wish to be active in the decision-making process; they may also have reduced cognitive function and family members may therefore have to step in as surrogate decision-makers. Informed consent is intended as a process of information giving and reflection, where consent can be withdrawn at any time. However, people are rarely updated on the altered risks and benefits of their long-term medications as they age. Cessation of inappropriate medication use has a large financial benefit to the individual and the community. However, the principle of justice also dictates equal rights to treatment regardless of age.     

Physical Activity in Non-Frail and Frail Older Adults

Introduction

Physical activity (PA) is important for healthy ageing. Better insight into objectively measured PA levels in older adults is needed, since most previous studies employed self-report measures for PA assessment, which are associated with overestimation of PA.

Aim

This study aimed to provide insight in objectively measured indoor and outdoor PA of older adults, and in PA differences by frailty levels.

Methods

Data were collected among non-frail (N = 74) and frail (N = 10) subjects, aged 65 to 89 years. PA, measured for seven days with accelerometers and GPS-devices, was categorized into three levels of intensity (sedentary, light, and moderate-to-vigorous PA).

Results

Older adults spent most time in sedentary and light PA. Subjects spent 84.7%, 15.1% and 0.2% per day in sedentary, light and moderate-to-vigorous PA respectively. On average, older adults spent 9.8 (SD 23.7) minutes per week in moderate-to-vigorous activity, and 747.0 (SD 389.6) minutes per week in light activity. None of the subjects met the WHO recommendations of 150 weekly minutes of moderate-to-vigorous PA. Age-, sex- and health status-adjusted results revealed no differences in PA between non-frail and frail older adults. Subjects spent significantly more sedentary time at home, than not at home. Non-frail subjects spent significantly more time not at home during moderate-to-vigorous activities, than at home.

Conclusions

Objective assessment of PA in older adults revealed that most PA was of light intensity, and time spent in moderate-to-vigorous PA was very low. None of the older adults met the World Health Organization recommendations for PA. These levels of MVPA are much lower than generally reported based on self-reported PA. Future studies should employ objective methods, and age specific thresholds for healthy PA levels in older adults are needed. These results emphasize the need for effective strategies for healthy PA levels for the growing proportion of older adults.     

Greater BOLD Variability in Older Compared with Younger Adults during Audiovisual Speech Perception

Older adults exhibit decreased performance and increased trial-to-trial variability on a range of cognitive tasks, including speech perception. We used blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to search for neural correlates of these behavioral phenomena. We compared brain responses to simple speech stimuli (audiovisual syllables) in 24 healthy older adults (53 to 70 years old) and 14 younger adults (23 to 39 years old) using two independent analysis strategies: region-of-interest (ROI) and voxel-wise whole-brain analysis. While mean response amplitudes were moderately greater in younger adults, older adults had much greater within-subject variability. The greatly increased variability in older adults was observed for both individual voxels in the whole-brain analysis and for ROIs in the left superior temporal sulcus, the left auditory cortex, and the left visual cortex. Increased variability in older adults could not be attributed to differences in head movements between the groups. Increased neural variability may be related to the performance declines and increased behavioral variability that occur with aging.     

Haematinic Deficiency and Macrocytosis in Middle-Aged and Older Adults

Objective

To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults.

Methods

A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT).

Results

The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%).

Conclusions

Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.