Susan D. Shenkin

Birth weight and cognitive ability in childhood: a systematic review.

Individual differences in cognitive ability may in part have prenatal origins. In high-risk (low birth weight/premature) babies, birth weight correlates positively with cognitive test scores in childhood, but it is unclear whether this holds for those with birth weights in the normal range. The authors systematically reviewed literature on the relationship between normal birth weight (more than 2,500 g) and childhood intelligence in term (37-42-week gestation) deliveries. Six studies met the inclusion criteria, and the authors present a comprehensive narrative review of these studies. There was a small, consistent, positive association between birth weight and childhood cognitive ability, even when corrected for confounders. Parental social class accounted for a larger proportion of the variance than birth weight, and these 2 variables were largely independent.

Birth weight and cognitive function at age 11 years: the Scottish Mental Survey 1932

AIMS To examine the relation between birth weight and cognitive function at age 11 years, and to examine whether this relation is independent of social class. METHODS Retrospective cohort study based on birth records from 1921 and cognitive function measured while at school at age 11 in 1932. Subjects were 985 live singletons born in the Edinburgh Royal Maternity and Simpson Memorial Hospital in 1921. Moray House Test scores from the Scottish Mental Survey 1932 were traced on 449 of these children. RESULTS Mean score on Moray House Test increased from 30.6 at a birth weight of <2500 g to 44.7 at 4001–4500 g, after correcting for gestational age, maternal age, parity, social class, and legitimacy of birth. Multiple regression showed that 15.6% of the variance in Moray House Test score is contributed by a combination of social class (6.6%), birth weight (3.8%), childs exact age (2.4%), maternal parity (2.0%), and illegitimacy (1.5%). Structural equation modelling confirmed the independent contribution from each of these variables in predicting cognitive ability. A model in which birth weight acted as a mediator of social class had poor fit statistics. CONCLUSION In this 1921 birth cohort, social class and birth weight have independent effects on cognitive function at age 11. Future research will relate these childhood data to health and cognition in old age.

Cerebral Microbleeds Are Associated With Lacunar Stroke Defined Clinically and Radiologically, Independently of White Matter Lesions

Background and Purpose— Associations among microbleeds, white matter lesions (WMLs), and small deep infarcts on imaging have been reported. Because many of these imaging infarcts were asymptomatic, the relationship of microbleeds to clinical lacunar stroke is unclear. An association between microbleeds and clinically defined lacunar stroke might suggest a common causal microangiopathy. Methods— Patients with lacunar, partial anterior circulation or posterior circulation stroke syndromes and older healthy subjects underwent MRI. Microhemorrhages, infarcts, hemorrhages, and WMLs were coded blind to clinical details. A final clinicoradiologic stroke subtype diagnosis was assigned. Results— Among 308 subjects (67 older healthy and 241 with stroke), 54 patients had microbleeds (17%). Microbleeds were twice as frequent in lacunar than cortical strokes (26% versus 13%, P=0.03) or healthy older subjects (9%) and associated with increasing WML scores (P<0.0001). Lacunar and cortical stroke subtypes and healthy older subjects had similar WML scores. Conclusions— Microbleeds are associated with lacunar stroke defined clinicoradiologically more than other stroke subtypes but not simply by association with WMLs. This suggests that microbleeds and lacunar stroke have a similar microvascular abnormality.

Tools to Detect Delirium Superimposed on Dementia: A Systematic Review

To identify valid tools to diagnose delirium superimposed on dementia.

Cognitive Correlates of Cerebral White Matter Lesions and Water Diffusion Tensor Parameters in Community-Dwelling Older People

Background: The biological basis of cognitive ageing is unknown. One underlying process might be disruption of white matter tracts connecting cortical regions. White matter lesions (WML) seen on structural MRI may disrupt cortical connections, but diffusion tensor MRI (DT-MRI) parameters – mean diffusivity () and fractional anisotropy (FA) – may reflect more subtle changes in white matter integrity. Here the relationships between WML load, DT-MRI parameters and cognition in a large cohort of elderly subjects with a very narrow age range were investigated. Methods: 105 community-dwelling volunteers underwent MRI and neuropsychological assessment. Seventy-two (68.6%) were female, and their mean age was 78.4 (SD 1.5) years. Scans were rated for WML load. and FA were measured from regions of interest in normal-appearing frontal and occipital white matter, and centrum semiovale. Results: and FA differed significantly among the three brain regions studied (p ≪ 0.01). increased with age (r = 0.22 to 0.35, p < 0.03), and was negatively correlated with FA (r = –0.20 to –0.51, p < 0.05) in all three regions. There was a trend towards increased WML load correlating with poorer cognitive function, and this was statistically significant for the Mini-Mental State Examination (ρ = –0.23, p = 0.02). was generally negatively correlated with cognitive test score, and FA was positively correlated. This pattern was more consistent for than for FA, and particularly for verbal fluency (: r = –0.22 to –0.27, p < 0.03), which measures executive function. Conclusions: DT-MRI parameters, in particular , are sensitive to early ultrastructural changes underlying cognitive ageing. Executive function may be the cognitive domain most sensitive to age-related decline in white matter tract integrity.

A Systematic Literature Review of Cerebrospinal Fluid Biomarkers in Delirium

Background: Cerebrospinal fluid (CSF) analysis has great potential to advance understanding of delirium pathophysiology. Methods: A systematic literature review of CSF studies of DSM or ICD delirium was performed. Results: In 8 studies of 235 patients, delirium was associated with: elevated serotonin metabolites, interleukin-8, cortisol, lactate and protein, and reduced somatostatin, β-endorphin and neuron-specific enolase. Elevated acetylcholinesterase predicted poor outcome after delirium and higher dopamine metabolites were associated with psychotic features. Conclusions: No clear conclusions emerged, but the current literature suggests multiple areas for further investigation with more detailed studies.

A systematic review of brain frontal lobe parcellation techniques in magnetic resonance imaging

Manual volumetric measurement of the brain’s frontal lobe and its subregions from magnetic resonance images (MRIs) is an established method for researching neural correlates of clinical disorders or cognitive functions. However, there is no consensus between methods used to identify relevant boundaries of a given region of interest (ROI) on MRIs, and those used may bear little relation to each other or the underlying structural, functional and connective architecture. This presents challenges for the analysis and synthesis of such results. We therefore performed a systematic literature review to highlight variations in the anatomical boundaries used to measure frontal regions, contextualised by up-to-date evidence from histology, hodology and neuropsychology. We searched EMBASE and MEDLINE for studies in English reporting three-dimensional boundaries for manually delineating the brain’s frontal lobe or sub-regional ROIs from MRIs. Exclusion criteria were: exclusive use of co-ordinate grid systems; insufficient detail to allow method replication; publication in grey literature only. Papers were assessed on quality criteria relating to bias, reproducibility and protocol rationale. There was a large degree of variability in the three-dimensional boundaries of all regions used by the 208 eligible papers. Half of the reports did not justify their rationale for boundary selection, and each paper met on average only three quarters of quality criteria. For the frontal lobe and each subregion (frontal pole, anterior cingulate, dorsolateral, inferior-lateral, and orbitofrontal) we identified reproducible methods for a biologically plausible target ROI. It is hoped that this synthesis will guide the design of future volumetric studies of cerebral structure.

Dementia in acute hospital inpatients: the role of the geriatrician

Dementia remains grossly underdiagnosed in the UK. Between 40 and 64% of those affected are not formally diagnosed [1–3]. Patients with dementia have high rates of hospital admission: around 6% of people with dementia are inpatients in general hospitals at a given time-point, compared with approximately 0.6% of over-65s without dementia. A recent study found that 42% of acute medical admissions of over-70s had dementia but only half had been diagnosed [2]. Patients with dementia in hospital are highly vulnerable. Prospective studies show higher mortality in people with dementia compared to those without [4] and mortality increases with dementia severity [5, 6]. For example, one study found that 24% of individuals with severe cognitive impairment died during their admission compared with 7.5% of individuals scoring over 23 on the Mini-Mental State Examination [2]. There are also increased rates of other adverse outcomes including delirium, incontinence, longer hospital stays and increased rates of new institutionalisation [7]. Every individual admitted to hospital receives an admission assessment including documentation of past medical history, a systems enquiry and physical examination to ensure relevant and co-existing pathology is not missed. Cognitive screening, analogous to the physical examination, is particularly important in de novo detection of dementia and indeed is universally recommended for all inpatients aged over 65 [8]. Yet the 2011 National Audit of Dementia Care in General Hospitals showed that having a relevant policy did not correlate with actual practice, for example 75% of hospitals advised mental state assessments but only 43% of casenotes examined had evidence of this being carried out [9]. This means that in the UK alone tens of thousands of people with undiagnosed dementia are admitted to and discharged from general hospitals without any cognitive testing or other cognition-specific assessments, with the consequence that their dementia remains undetected and untreated. Policymakers increasingly recognise the importance of detecting and effectively managing dementia in hospital inpatients [9–13]. More generally, there is consensus that appropriate diagnosis of dementia benefits patients [7]. The advantages of diagnosis and subsequent treatment include access to drug treatments, appropriate multidisciplinary care and allowing patients and carers to plan for the future. Indeed, patients generally welcome the idea of knowing the diagnosis [14]. Because hospital patients with dementia are relatively more likely to have contact with a geriatrician, undiagnosed dementia is present in a large proportion of patients under their care in both acute and rehabilitation settings. Why then do geriatricians not routinely aim to detect previously undiagnosed dementia in their inpatients? Obstacles to dementia diagnosis in primary care are well recognised [15] but less is known about secondary care. Many clinicians, including geriatricians, hesitate to diagnose dementia [16] because of the possibility of an incorrect diagnosis causing unnecessary anxiety and social withdrawal, concerns about paternalism, stigma, medication side-effects, further strain on families and, perhaps, greater demands on services [15]. Others hesitate because of fears it will complicate the process of discharge and appropriate placement [17]. Additionally, the current structure of training in medicine of the elderly (MoE) in the UK does not universally include training in the assessment and diagnosis of cognitive disorders; therefore, professional under-confidence in this domain will also hamper recognition and diagnosis. These are all important considerations, but with care and adequate training, most can be overcome or mitigated. Ethical guidance also highlights the interests of carers— who may be keen for a diagnosis to be made [18]. What practical steps might be taken? With respect to dementia detection in the general hospital there are two main challenges. The first is identifying individuals already diagnosed with dementia and ensuring they receive appropriately tailored care including delirium prevention and close liaison with family. Establishing the presence or absence of a prior formal diagnosis of dementia in general hospitals can be time consuming. Terms such as ‘confusion’ or ‘cognitive impairment’ often appear in general hospital notes or letters from general practitioners, but it is unclear how these labels have been arrived at. Prior cognitive testing results may be present in the notes but it is often not known if the patient had delirium at the time of testing. The separation of psychiatric and general medical records in many hospitals impedes simple transcription of clinical These proportions were calculated from the following UK estimates: 140,000 hospital beds, approximately two-thirds occupied by older adults, 10 million adults over 65, 600,000 individuals with dementia and a hospital prevalence of dementia of approximately 25%.

CT and Clinical Predictors of Fatigue at One Month after Stroke

Background: Fatigue is a common and distressing consequence of stroke, and the aetiology of post-stroke fatigue (PSF) is poorly understood. It is unclear whether chronic brain changes [cerebral atrophy and white matter lesions (WML)], stroke lesion location or certain clinical features are related to its development. The aim of this study was to identify, in patients with acute stroke, whether features in different brain regions on routine CT imaging or routinely collected clinical features predicted PSF at 1 month. Methods: In total, 107 patients (62% male) with acute ischaemic or haemorrhagic stroke were assessed for fatigue (Fatigue Assessment Scale), anxiety and depression (Hospital Anxiety and Depression Scale) at 1 month. Admission brain CT was rated using a structured scoring system for (i) severity of atrophy and (ii) severity of WML in different regions of the brain, and (iii) site of acute and previous vascular lesions. Results: Cerebral atrophy of mild or greater severity was present in 84 patients (77.5%) and WML of mild or greater severity was present in 54 patients (50.5%) in at least one of the evaluated brain regions. There was no association between PSF and severity of atrophy or WML, or presence of acute or previous vascular lesions. We used the Oxfordshire Community Stroke Project (OCSP) classification to explore the possible influence of lesion location because a minority of the patients (37.4%) had visible acute lesions. Fatigue scores were higher in patients with clinically diagnosed posterior strokes (p = 0.046), in females (p = 0.05) and in those with higher depression and anxiety scores (ρ = 0.52; p < 0.001 and ρ = 0.49; p < 0.001, respectively). Structural CT variables were not significant predictors of fatigue (log FAS) in a linear regression which controlled for age, sex, pre-stroke fatigue, OCSP classification, depression and anxiety. The significant predictors of fatigue were depression (β = 0.30; p = 0.007) and anxiety (β = 0.28; p = 0.013; adjusted R2 = 0.254). Stroke subtype (according to the OCSP classification) was marginally predictive (β = 0.17; p = 0.05) and sex was not statistically significant (β = 0.15; p = 0.08). Conclusions: Features on routine post-stroke CT do not appear to associate with fatigue at 1 month. However, clinically diagnosed posterior strokes as well as female gender, anxiety and depression may be linked with fatigue. Therefore, clinical vigilance rather than CT features should be used to predict fatigue early after stroke. Further research is needed in this area to establish whether biological mechanisms underlie the development of PSF.

Development of a smartphone application for the objective detection of attentional deficits in delirium.

BACKGROUND Delirium is an acute, severe deterioration in mental functioning. Inattention is the core feature, yet there are few objective methods for assessing attentional deficits in delirium. We previously developed a novel, graded test for objectively detecting inattention in delirium, implemented on a computerized device (Edinburgh Delirium Test Box (EDTB)). Although the EDTB is effective, tests on universally available devices have potential for greater impact. Here we assessed feasibility and validity of the DelApp, a smartphone application based on the EDTB. METHODS This was a preliminary case-control study in hospital inpatients (aged 60-96 years) with delirium (N = 50), dementia (N = 52), or no cognitive impairment (N = 54) who performed the DelApp assessment, which comprises an arousal assessment followed by counting of lights presented serially. Delirium was assessed using the Confusion Assessment Method and Delirium Rating Scale-Revised-98 (DRS-R98), and cognition with conventional tests of attention (e.g. digit span) and the short Orientation-Memory-Concentration Test (OMCT). RESULTS DelApp scores (maximum score = 10) were lower in delirium (scores (median(IQR)): 6 (4-7)) compared to dementia (10 (9-10)) and control groups (10 (10-10), p-values < 0.001). Receiver operating characteristic (ROC) analyses revealed excellent accuracy of the DelApp for discriminating delirium from dementia (AUC = 0.93), and delirium from controls (AUC = 0.99, p-values < 0.001). DelApp and DRS-R98 severity scores were moderately well correlated (Kendalls tau = -0.60, p < 0.001). OMCT scores did not differ between delirium and dementia. CONCLUSIONS The DelApp test showed good performance, supporting the utility of objectively measuring attention in delirium assessment. This study provides evidence of the feasibility of using a smartphone test for attentional assessment in hospital inpatients with possible delirium, with potential applications in research and clinical practice.