A Call for Research on the Validity of the Age-of-Onset Criterion Application in Older Adults Being Evaluated for ADHD: A Review of the Literature in Clinical and Cognitive Psychology

Roughly 3% of adults aged 50 years or older experience significant symptoms of attention-deficit/hyperactivity disorder (ADHD). They are often diagnosed for the first time in later adulthood, because ADHD is a relatively new diagnosis with only recent awareness of later-life cases, and because many symptomatic adults have high early-life functioning due to supportive environmental and social structures. Current Diagnostic and Statistical Manual of Mental Disorders-5 criteria require evidence of symptom onset prior to age 12, which rests on self-report in older adults for whom ancillary sources are unavailable or unreliable. In this review, we summarize evidence from several bodies of literature which suggest this criterion may be invalid in older adults. The authors hypothesize that demonstrating childhood symptom onset in older adults is not feasible (i.e., no awareness of ADHD prior to 1970; no good current ancillary sources of childhood behaviors), unreliable (i.e., severely flawed retrospective self-report) and unethical (i.e., unreasonable denial of support to people who need it, with demonstrated poor outcomes associated with untreated ADHD in adults). The authors outline additional research that is needed to establish the validity of self-reported childhood symptom onset in this under-studied demographic, including the identification of contextual factors (perhaps unique to late life) that are associated with the emergence of ADHD symptoms in older adulthood; determining the impact of memory biases on recall of childhood symptoms in older adults with ADHD; quantifying self-perception deficits; and investigating the usefulness of executive functioning rating scales to complement diagnostic assessment in older adults.     

ABA Versus TEACCH: The Case for Defining and Validating Comprehensive Treatment Models in Autism

The authors analyzed the results of a social validation survey to determine if autism service providers including special education teachers, parents, and administrators demonstrate a preference for the intervention components of Applied Behavior Analysis or Training and Education of Autistic and other Communication Handicapped Children. They also investigated the comprehensiveness of these treatment models for use in public school programs. The findings indicate no clear preference for either model, but a significantly higher level of social validity for components inherent in both approaches. The authors discuss the need for research to define what is meant by comprehensive programming in autism.     

Timing of do-not-resuscitate orders for hospitalized older adults who require a surrogate decision-maker

OBJECTIVES: To examine the frequency of surrogate decisions for in‐hospital do‐not‐resuscitate (DNR) orders and the timing of DNR order entry for surrogate decisions. DESIGN: Retrospective cohort study. SETTING: Large, urban, public hospital. PARTICIPANTS: Hospitalized adults aged 65 and older over a 3‐year period (1/1/2004–12/31/2006) with a DNR order during their hospital stay. MEASUREMENTS: Electronic chart review provided data on frequency of surrogate decisions, patient demographic and clinical characteristics, and timing of DNR orders. RESULTS: Of 668 patients, the ordering physician indicated that the DNR decision was made with the patient in 191 cases (28.9%), the surrogate in 389 (58.2%), and both in 88 (13.2%). Patients who required a surrogate were more likely to be in the intensive care unit (62.2% vs 39.8%, P<.001) but did not differ according to demographic characteristics. By hospital Day 3, 77.6% of patient decisions, 61.9% of surrogate decisions, and 58.0% of shared decisions had been made. In multivariable models, the number of days from admission to DNR order was higher for surrogate (odds ratio (OR)=1.97, P<.001) and shared decisions (OR=1.48, P=.009) than for patient decisions. The adjusted hazard ratio for hospital death was higher for patients with surrogate than patient decisions (2.61, 95% confidence interval (CI)=1.56–4.36). Patients whose DNR orders were written on Day 6 or later were twice as likely to die in the hospital (OR=2.20, 95% CI=1.45–3.36) than patients with earlier DNR orders. CONCLUSION: For patients who have a DNR order entered during their hospital stay, order entry occurs later when a surrogate is involved. Surrogate decision‐making may take longer because of the greater ethical, emotional, or communication complexity of making decisions with surrogates than with patients.     

RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents

Neuronal nicotinic α7 acetylcholine receptors (α7nAChRs) are expressed primarily in the brain and are implicated in modulating many cognitive functions (e.g., attention, working and episodic memory). Not surprisingly, much effort has been committed to the development of molecules acting at α7nAChRs as potential therapies for a variety of central nervous system diseases (e.g., Alzheimer's). N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-1H-indazole-3-carboxamide hydrochloride (RG3487) binds potently to the human α7nAChR (K(i) = 6 nM), in which it acts as a partial agonist (63-69% of acetylcholine) as assessed by whole-cell patch-clamp recordings in both oocytes and QM7 cell lines. RG3487 activates human α7nAChRs with an EC(50) of 0.8 μM (oocytes) and 7.7 μM (QM7 cells). RG3487 also exhibits antagonist properties at the serotonin 3 receptor [IC(50) = 2.8 nM (oocytes), 32.7 nM (N1E-115 cells)]. In vivo, RG3487 improved object recognition memory in rats after acute [minimally effective dose (MED) 1.0 mg/kg p.o.] or repeated (10 day) administration at brain and plasma concentrations in the low-nanomolar range. Spatial learning deficits in age-impaired rats were reversed after RG3487 administration (MED: 0.03 mg/kg i.p.) as evaluated in the Morris water maze task. In the prepulse inhibition (PPI) of startle model of sensorimotor gating, RG3487 improved apomorphine-induced deficits in PPI performance (MED: 0.03 mg/kg i.p.) and reversed phencyclidine-induced impairments in an attentional set-shifting model of executive function (MED: ≤0.03 mg/kg i.p.). Cumulative evidence from these studies indicates RG3487 is a novel and potent α7nAChR partial agonist that improves cognitive performance and sensorimotor gating.