Dimitrios Adamis

A longitudinal study of motor subtypes in delirium: Relationship with other phenomenology, etiology, medication exposure and prognosis

OBJECTIVE Motor subtypes have promise as a means of identifying clinically relevant delirium subgroups. Little is known about their relationship to etiologies, medication exposure, and outcomes. METHODS Consecutive cases of DSM-IV delirium in palliative care patients were assessed twice-weekly throughout their delirium episodes using the Delirium Motor Subtype Scale (DMSS), Delirium Etiology Checklist (DEC) and Delirium Rating Scale Revised-98 (DRS-R98). RESULTS 100 patients [mean age 70.2 ± 10.5] were assessed on 303 visits [range 2-9]. Over the entire episode, mean DRS-R98 Severity scores were 16.2 ± 5.7. The mean number of etiologies per case was 3.4 ± 1.2. Motor subtypes were no subtype throughout (6%), hypoactive subtype throughout (28%), mixed subtype throughout (18%), hyperactive subtype throughout (10%) and variable subtype (38%). DRS-R98 Total and Severity scales differed significantly across categories (highest in mixed) but only motor, sleep-wake cycle, perceptual and language disturbance items differed. The Generalized Estimating Equations (GEE) approach was used to explore the relationship between subtype profile and symptoms, medication exposure and etiology. This showed that apart from motor items, only delusions, affective lability, metabolic disturbance and CVA related to any subtype. Cross-sectional assessments indicated greater use of benzodiazepine and antipsychotics in hyperactive patients but GEE analyses did not identify major associations between motor subtype and medication exposure. Patients with sustained hypoactive subtype were significantly more likely to die within one month of study entry. CONCLUSIONS Motor profile in delirium is relatively consistent over episode course and relates more closely to delirium phenomenology than to etiology or medication exposure. Motor subtypes have comparable disturbance of key diagnostic features such as cognitive and thought process abnormalities. Although mixed subtype is the most phenomenologically intense, hypoactives have the poorest prognosis.

Features of subsyndromal and persistent delirium

BACKGROUND Longitudinal studies of delirium phenomenology are lacking. AIMS We studied features that characterise subsyndromal delirium and persistent delirium over time. METHOD Twice-weekly evaluations of 100 adults with DSM-IV delirium using the Delirium Rating Scale-Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). The generalised estimating equation method identified symptom patterns distinguishing full syndromal from subsyndromal delirium and resolving from persistent delirium. RESULTS Participants (mean age 70.2 years (s.d. = 10.5)) underwent 323 assessments (range 2-9). Full syndromal delirium was significantly more severe than subsyndromal delirium for DRS-R98 thought process abnormalities, delusions, hallucinations, agitation, retardation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance, orientation and memory. Persistent full syndromal delirium had greater disturbance of DRS-R98 thought process abnormalities, delusions, agitation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance and orientation. CONCLUSIONS Full syndromal delirium differs from subsyndromal delirium over time by greater severity of many cognitive and non-cognitive symptoms. Persistent delirium involves increasing prominence of recognised core diagnostic features and cognitive impairment.

A brief review of the history of delirium as a mental disorder

We review the most important concepts about delirium, from ancient times until the twentieth century. We also focus on the question of how these concepts have dealt with the particular problems posed by prognosis and outcome. Althought different terms have been used, a robust description of delirium has existed since antiquity — at some times as a symptom and at others as a syndrome. It is clear that, throughout the millennia, delirium has been — and still is — a highly lethal syndrome; a poor mental outcome for survivors was often noted. Not until the twentieth century was it thought that delirium was marked by a full recovery among survivors, and this was probably due to the desire for a clear distinction from dementia.

The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta‐analysis

Delirium is the most common neuropsychiatric syndrome in elderly ill patients. Previously, associations between delirium and the dopamine transporter gene (solute carrier family 6, member 3 (SLC6A3)) and dopamine receptor 2 gene (DRD2) were found. The aim of this study was to validate whether markers of the SLC6A3 and DRD2 genes are were associated with delirium in independent populations. Six European populations collected DNA of older delirious patients. Associations were determined per population and results were combined in a meta‐analysis. In total 820 medical inpatients, 185 cardiac surgery patients, 134 non‐cardiac surgery patients and 502 population‐based elderly subjects were included. Mean age was 82 years (SD 7.5 years), 598 (36%) were male, 665 (41%) had pre‐existing cognitive impairment, and 558 (34%) experienced delirium. The SLC6A3 rs393795 homozygous AA genotype was more frequent in patients without delirium in all populations. The meta‐analysis showed an Odds Ratio (OR) for delirium of 0.4 (95% confidence interval (C.I.) 0.2–0.6, P = 0.0003) for subjects with AA genotype compared to the AG and GG genotypes. SLC6A3 marker rs1042098 showed no association with delirium. In meta‐analysis the DRD2 rs6276 homozygous GG genotype showed an OR of 0.8 for delirium (95% C.I. 0.6–1.1, P = 0.24). When subjects were stratified for cognitive status the rs6276 GG genotype showed ORs of 0.6 (95% C.I. 0.4–1.0, P = 0.06) and 0.8 (95% C.I. 0.5–1.5, P = 0.51) for delirium in patients with and without cognitive impairment, respectively. In independent cohorts, a variation in the SLC6A3 gene and possibly the DRD2 gene were found to protect for delirium.

Ethical Challenges and Solutions Regarding Delirium Studies in Palliative Care

CONTEXT Delirium occurs commonly in settings of palliative care (PC), in which patient vulnerability in the unique context of end-of-life care and delirium-associated impairment of decision-making capacity may together present many ethical challenges. OBJECTIVES Based on deliberations at the Studies to Understand Delirium in Palliative Care Settings (SUNDIPS) meeting and an associated literature review, this article discusses ethical issues central to the conduct of research on delirious PC patients. METHODS Together with an analysis of the ethical deliberations at the SUNDIPS meeting, we conducted a narrative literature review by key words searching of relevant databases and a subsequent hand search of initially identified articles. We also reviewed statements of relevance to delirium research in major national and international ethics guidelines. RESULTS Key issues identified include the inclusion of PC patients in delirium research, capacity determination, and the mandate to respect patient autonomy and ensure maintenance of patient dignity. Proposed solutions include designing informed consent statements that are clear, concise, and free of complex phraseology; use of concise, yet accurate, capacity assessment instruments with a minimally burdensome schedule; and use of PC friendly consent models, such as facilitated, deferred, experienced, advance, and proxy models. CONCLUSION Delirium research in PC patients must meet the common standards for such research in any setting. Certain features unique to PC establish a need for extra diligence in meeting these standards and the employment of assessments, consent procedures, and patient-family interactions that are clearly grounded on the tenets of PC.

Delirium motor subtypes in elderly hip fracture patients: Risk factors, outcomes and longitudinal stability

OBJECTIVE Delirium is often accompanied by changes in motor activity but the longitudinal expression of these features and etiological and prognostic significance of clinical subtypes defined by motor activity is unclear. METHODS This is a prospective cohort study of elderly patients undergoing hip fracture surgery. Baseline characteristics were assessed preoperatively. During hospital admission presence of delirium was assessed daily according to CAM criteria. This study compared baseline characteristics and outcomes according to a longitudinal pattern of motor subtype expression (predominantly hyperactive, predominantly hypoactive, predominantly mixed, no motor subtype and variable). Motor subtype categorization was performed with the DRS-R98. We also investigated the longitudinal stability of motor subtypes across the delirium episode. RESULTS 62 patients had experienced in-hospital delirium postoperatively. The full course of the delirium episode could be defined for 42/62 (67.7%) patients. Of the patients with multiple days of delirium only 4/30 (13.3%) patients had a consistent motor subtype profile throughout the delirium episode, while 26/30 (86.7%) patients had a variable course. Of the patients with multiple days of delirium, 5/30 (16.7%) were predominantly hypoactive in profile, 7/30 (23.3%) predominantly hyperactive, 6/30 (20%) predominantly mixed, 1/30 (3.3%) had no motor subtype and 11/30 (36.7%) had a variable profile. Baseline characteristics and outcomes did not differ between the groups. CONCLUSION The majority of elderly hip fracture patients in this homogenous sample experienced variable expression of motor subtype over the course of their delirium episodes. The subtype categorization according to dominant motor subtype across the delirium episode identified groups with similar characteristics and outcomes.

Insulin-Like Growth Factor I and the Pathogenesis of Delirium: A Review of Current Evidence

Delirium is a frequent complication in medically ill elderly patients that is associated with serious adverse outcomes including increased mortality. Delirium risk is linked to older age, dementia, and illness that involves activation of inflammatory responses. IGF-I is increasingly postulated as a key link between environmental influences on body metabolism with a range of neuronal activities and has been described as the master regulator of the connection between brain and bodily well-being. The relationships between IGF-I and ageing, cognitive impairment and inflammatory illness further support a possible role in delirium pathogenesis. Five studies of IGF-I in delirium were identified by a systematic review. These conflicting findings, with three of the five studies indicating an association between IGF-1 and delirium occurrence, may relate to the considerable methodological differences in these studies. The relevance of IGF-I and related factors to delirium pathogenesis can be clarified by future studies which account for these issues and other confounding factors. Such work can inform therapeutic trials of IGF-I and/or growth hormone administration.

The genetics of deliria

Delirium not induced by alcohol or other psychoactive substance and alcohol withdrawal delirium (or delirium tremens) are both cerebral syndromes with similar presentations and are associated with various adverse outcomes. Recently, interest in identifying genetic predisposing factors that influence the occurrence or the outcome of delirium has become a prominent point of delirium research. We systematically searched published articles concerning genetic associations and the occurrence and outcome of delirium. Of 33 identified articles, six investigated non-alcohol withdrawal delirium, and from those six, five evaluated an association with apolipoprotein E (APOE). One association of APOE genotype with the emergence of delirium and two associations of APOE genotype with the duration of delirium were reported. The remaining 27 identified articles investigated genetic associations with alcohol withdrawal delirium and were mainly related to dopamine. Two studies reported a significant association of alcohol withdrawal delirium with the dopamine transporter gene (SLC6A3) and the dopamine receptor 3 (DRD3). Results are inconclusive, and no hard evidence exists due primarily to insufficiently powered studies and other methodological issues. Prospective studies incorporating systematic and rigorous diagnostic criteria and involving long term follow up are needed to advance understanding of this field.

Validation and psychometric properties of the Delirium Motor Subtype Scale in elderly hip fracture patients (Dutch version)

The Delirium Motor Subtype Scale (DMSS) was developed to capture all the previous different approaches to delirium motor subtyping into one new instrument and emphasize disturbances of motor activity rather than associated psychomotoric symptoms. We investigated reliability and validity of the DMSS Dutch version. Elderly patients who had undergone hip fracture surgery received the DMSS and the Delirium Rating Scale Revised-98 (DRS-R-98). A diagnosis of delirium was defined according to the Confusion Assessment Method (CAM). Among 146 patients, 46 (32%) patients were diagnosed with delirium (mean age 86.3 years; SD 5.2). The internal consistency of the DMSS was acceptable (Cronbachs alpha=0.72). If an item was removed at random the internal consistency of the scale remained the same. Similarly the concurrent validity of DMSS was good (Cohens kappa=0.73) while for each motor subtype the Cohens kappa ranged from 0.58 to 0.85. The sensitivity and specificity of DMSS to detect each subtype ranged from 0.56 to 1 and from 0.88 to 0.98, respectively. This study suggests that the Dutch version of the DMSS is a reliable and valid instrument. The DMSS has scientific validity that could allow for greater precision in further research on motor subtypes.

Concordance between the delirium motor subtyping scale (DMSS) and the abbreviated version (DMSS-4) over longitudinal assessment in elderly medical inpatients.

BACKGROUND Delirium is a common neuropsychiatric syndrome that includes clinical subtypes identified by the Delirium Motor Subtyping Scale (DMSS). We explored the concordance between the DMSS and an abbreviated 4-item version in elderly medical inpatients. METHODS Elderly general medical admissions (n = 145) were assessed for delirium using the Revised Delirium Rating scale (DRS-R98). Clinical subtype was assessed with the DMSS (which includes the four items included in the DMSS-4). Motor subtypes were generated for all patient assessments using both versions of the scale. The concordance of the original and abbreviated DMSS was examined. RESULTS The agreement between the DMSS and DMSS-4 was high, both at initial and subsequent assessments (κ range 0.75-0.91). Intraclass Correlation Coefficient (ICC) for all three raters for the DMSS was high (0.70) and for DMSS-4 was moderate (0.59). Analysis of the agreement between raters for individual DMSS items found higher concordance in respect of hypoactive features compared to hyperactive. CONCLUSIONS The DMSS-4 allows for rapid assessment of clinical subtype in delirium and has high concordance with the longer and well-validated DMSS, including over longitudinal assessment. There is good inter-rater reliability between medical and nursing staff. More consistent clinical subtyping can facilitate better delirium management and more focused research effort.