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Bulletin vol. 34 no. 1 | 25 Of the five most cited articles in the Journal of the American Medical Association—Neurology over the last three years that focused on adult life-span research, three are of direct interest to neuropsychology and clinical neuropsychologists. In the five most cited in JAMA-Psychiatry over the last three years, two may be of the most interest to clinical neuropsychologists. In the first of the Neurology papers, Mattsson and colleagues (PMID: 28346578) in Sweden reported on neurofilament light (NFL), a blood-based biomarker. NFL is a protein that is highly expressed in myelinated axons. An increase in the blood and CSF is thought to represent axonal damage in a variety of conditions. The authors used a very sensitive assay (Simoa) to detect NFL levels in the serum in a group of healthy controls, those with AD dementia and those with MCI. High levels of NFL were seen in patients with AD and MCI compared to controls. The levels correlated with poor performance on cognitive tests and brain atrophy on imaging. This study is the first to show a peripheral, non-invasive biomarker that showed diagnostic accuracy for AD. Of caution however, the authors concluded that, "we do not envision plasma NFL as a tool to differentiate AD from other neurodegenerative diseases. Rather, it may be valuable as a general biomarker for neurodegeneration." In the second paper, Crane and colleagues (PMID: 27400367) examined the association of traumatic brain injury (TBI) with late life dementia and Parkinson disease. This study combined data from three prospective studies with a total of over 7,000 participants over 45,000 person years. The studies had obtained self-reported information on TBI earlier in life and had followed the study subjects over time. Over 1,500 had neuropathological studies after death. The authors concluded that TBI with LOC is associated with risk for Lewy body accumulation, progression of parkinsonism, and PD, but not dementia, AD, neuritic plaques, or neurofibrillary tangles. Some differences were found when duration of loss of consciousness was less than one hour. The third study, by Wang and Colleagues (PMID: 27454922), examined the use of PET ligands to look at tau in living controls and AD patients to examine the value in diagnosing or staging AD. Fifty-nine subjects with a mean age of 76 received the PET scan, as well as structural MRI and a lumbar puncture to look at CSF levels of total tau, ptau and Aβ42. The binding of [18F]- AV-1451 (the PET ligand) in the hippocampus and AD cortical signature regions accurately distinguished AD from control participants. Additionally, the cortical tau binding was elevated in the presence of Aβ. This suggests that interactions between tau and Aβ are important in the process of degeneration in AD. Aβ may intensify the spread of tauopathy and in the hippocampus, "Aβ likely transforms preexisting tauopathy to a more toxic species that results in neuronal injury." In the first of the two Psychiatry papers, Karyotaki and colleagues in Europe (PMID: 28241179) performed a meta-analysis of participant data from over 3,800 adults from 16 studies. The question was whether self-guided internet-based cognitive behavioral therapy was effective in treating depressive symptoms and which variables moderated that treatment outcome. Subjects who participated in self-guided iCBT had lower depressive symptom severity and greater treatment response compared with subjects in control conditions. Further, the intervention appeared to be effective for individuals with depressive symptoms regardless of the severity of their symptoms or their sociodemographic background. The second paper is a consensus statement on the use of ketamine in the treatment of mood disorders. Sanacora and colleagues (PMID: 28249076) provide an overview of existing knowledge about ketamine's use in treating depressive disorders and the potential risks associated with it. Among the cautions raised, besides concerns about the physiologic effects during infusion and afterwards, were the effects on mental status (e.g., possible impairments in driving, etc.) as well as frank cognitive impairment when repeated doses are given. It was suggested that cognitive assessments be considered in the case of repeated usage. This was partially based on a 2004 paper (PMID:15283951) that suggested that repeated use of ketamine produces chronic impairments in episodic memory. Louis M. French, PsyD Deputy Director, National Intrepid Center of Excellence Walter Reed National Military Medical Center Associate Professor of Neurology and Rehabilitation F. Edward Hebert School of Medicine Uniformed Services University of the Health Sciences Co-Director, Phenotyping Core Center for Neuroscience and Regenerative Medicine NIH/USUHS Most Influential Articles Published in JAMA Neurology and JAMA Psychiatry Over the Last Three Years

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