Classification Criteria and Rates of Persistent Postconcussive Symptoms in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To provide a systematic review of studies examining the proportion of children with persistent postconcussive symptoms (PPCS) and to examine potential moderators of prevalence. STUDY DESIGN: Searches were conducted in MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Central Register of Controlled Trials on April 16, 2020. Criteria for study inclusion were children aged <18 years with concussion or mild traumatic brain injury, operational definition of PPCS, assessment of postconcussive symptoms at least 4 weeks postinjury, sample sizes and proportion with PPCS available, and study published in English. Definition of PPCS, sample size, proportion of participants identified with PPCS, child sex and age at injury, time postinjury, premorbid symptoms, diagnosis (concussion or mild traumatic brain injury), and study publication year were extracted from each article. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Thirteen studies, with a total of 5307 participants, were included in our analysis. The proportion of children identified with PPCS was 35.1% (weighted average; 95% CI, 26.3%-45.0%). The prevalence of PPCS was higher in older and female children who presented for care at concussion clinics, and in more recent publications. CONCLUSIONS: Approximately one-third of children with concussion/mild traumatic brain injury will experience PPCS. Age, sex, and point of care could help identify children at high risk for PPCS.

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.

Characterizing mild cognitive impairment to predict incident dementia in adults with bipolar disorder: What should the benchmark be?

Objective: Although mild cognitive impairment (MCI) is generally considered a risk state for dementia, its prevalence and association with dementia are impacted by the number of tests and cut-points used to assess cognition and define "impairment," and sources of norms. Here, we investigate how these methodological variations impact estimates of incident dementia in adults with bipolar disorder (BD), a vulnerable population with pre-existing cognitive deficits and increased dementia risk. Method: Neuropsychological data from 148 adults with BD and 13,610 healthy controls (HC) were drawn from the National Alzheimer's Coordinating Center. BD participants' scores were standardized against published norms and again using regression-based norms generated from HC within the same catchment area as individual BD patients ("site-specific norms"), varying the number of within-domain tests (one vs. two) and the cut-points (-1 vs. -1.5 SD) used to operationalize MCI. Results: Site-specific norms were more sensitive to incident dementia (88.6%-94.3%) than published norms (74.3%-88.6%), but only when using a "single test" definition of impairment. Specificity (22.1%-74.3%), accuracy (37.8%-68.9%), and positive predictive values (26.1%-38.3%) were overall poor. Applying a "single test" definition of impairment resulted in better negative predictive values using site-specific (92.3%-93.3%) than published norms (83.6%-86.2%), and a substantial increase in relative risk of incident dementia relative to published norms. Conclusions: Neuropsychologists should define "impairment" as scores below -1.0 or -1.5 SD on at least two within-domain measures when using published norms to interpret cognitive performance in adults with BD.

Cerebrovascular and Neurodegenerative Pathologies in Long-Term Stable Mild Cognitive Impairment.

BACKGROUND: Mild cognitive impairment (MCI) is considered by some to be a prodromal phase of a progressive disease (i.e., neurodegeneration) resulting in dementia; however, a substantial portion of individuals (ranging from 5-30%) remain cognitively stable over the long term (sMCI). The etiology of sMCI is unclear but may be linked to cerebrovascular disease (CVD), as evidence from longitudinal studies suggest a significant proportion of individuals with vasculopathy remain stable over time. OBJECTIVE: To quantify the presence of neurodegenerative and vascular pathologies in individuals with long-term (>5-year) sMCI, in a preliminary test of the hypothesis that CVD may be a contributor to non-degenerative cognitive impairment. We expect frequent vasculopathy at autopsy in sMCI relative to neurodegenerative disease, and relative to individuals who convert to dementia. METHODS: In this retrospective study, using data from the National Alzheimer's Coordinating Center, individuals with sMCI (n = 28) were compared to those with MCI who declined over a 5 to 9-year period (dMCI; n = 139) on measures of neurodegenerative pathology (i.e., Aß plaques, neurofibrillary tangles, TDP-43, and cerebral amyloid angiopathy) and CVD (infarcts, lacunes, microinfarcts, hemorrhages, and microbleeds). RESULTS: Alzheimer's disease pathology (Aß plaques, neurofibrillary tangles, and cerebral amyloid angiopathy) was significantly higher in the dMCI group than the sMCI group. Microinfarcts were the only vasculopathy associated with group membership; these were more frequent in sMCI. CONCLUSION: The most frequent neuropathology in this sample of long-term sMCI was microinfarcts, tentatively suggesting that silent small vessel disease may characterize non-worsening cognitive impairment.

ADHD and Neurodegenerative Disease Risk: A Critical Examination of the Evidence.

In this review, we undertake a critical appraisal of eight published studies providing first evidence that a history of attention-deficit/hyperactivity disorder (ADHD) may increase risk for the later-life development of a neurodegenerative disease, in particular Lewy body diseases (LBD), by up to five-fold. Most of these studies have used data linked to health records in large population registers and include impressive sample sizes and adequate follow-up periods. We identify a number of methodological limitations as well, including potential diagnostic inaccuracies arising from the use of electronic health records, biases in the measurement of ADHD status and symptoms, and concerns surrounding the representativeness of ADHD and LBD cohorts. Consequently, previously reported risk associations may have been underestimated due to the high likelihood of potentially missed ADHD cases in groups used as "controls", or alternatively previous estimates may be inflated due to the inclusion of confounding comorbidities or non-ADHD cases within "exposed" groups that may have better accounted for dementia risk. Prospective longitudinal studies involving well-characterized cases and controls are recommended to provide some reassurance about the validity of neurodegenerative risk estimates in ADHD.