The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

https://homepage.univie.ac.at/peter.dal-bianco/memory-clinic/mcipetersen.pdf

Current concepts in mild cognitive impairment.

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Systematic review of levodopa dose equivalency reporting in Parkinson's disease

Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

/pdf/diagnosis-and-management-of-dementia-with-lewy-bodies-fourth-bauvdvbrlh.pdf

Diagnosis and management of dementia with Lewy bodies Fourth consensus report of the DLB Consortium

Para-suicidal amnestic behavior associated with chronic zolpidem use: implications for patient safety.

https://www.sleep.theclinics.com/article/S1556-407X(05)00006-8/pdf

The Investigation of Sleepiness

Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive hereditary disease of the white matter caused by duplication of the nuclear lamina protein lamin B1 on chromosome 5q23.2.1 Patients usually present in the 4th–5th decade with autonomic symptoms followed by pyramidal and cerebellar dysfunction.2 In ADLD, MRI head reveals symmetric T2-signal hyperintensities in the subcortical white matter, brainstem, and middle cerebellar peduncles.2 REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment behavior and REM sleep without atonia.3 It has been reported most commonly with synucleinopathies such as Parkinson disease and may precede the diagnosis by decades.3 To our knowledge, RBD has not been reported with leukodystrophies. Herein we report a case of ADLD presenting with RBD as the initial symptom.

Adult-onset autosomal dominant leukodystrophy presenting with REM sleep behavior disorder

Amiodarone-associated neuromyopathy: a report of four cases E. P. Flanagan, C. M. Harper, E. K. St Louis M. H. Silber and K. A. Josephs Department of Neurology, Mayo Clinic, Rochester, MN, USA Correspondence: Dr Keith A. Josephs, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA (tel.: +15075380138; fax: +15072664752; e-mail: josephs.keith@mayo.edu).

Amiodarone‐associated neuromyopathy: a report of four cases

There has been no comparison of excessive daytime sleepiness (EDS) in patients with Alzheimer's disease dementia (AD), dementia with Lewy bodies (DLB), and behavioral variant frontotemporal dementia (bvFTD). We identified patients with mild dementia who met criteria for these disorders who also had the Epworth Sleepiness Scale (ESS) completed. The sample included 17 bvFTD, 111 AD, and 31 DLB. An ESS score ≥10 was considered abnormal and consistent with EDS. Analyses with age and sex as covariates revealed higher mean ESS scores for DLB compared to the other groups (DLB 13.9 [5], bvFTD 9.6 [8], AD 8.8 [5], P < .05). An ESS score ≥10 was significantly more likely to occur in DLB compared to bvFTD or AD (DLB 81% vs bvFTD 47% vs AD 45%, P < .01). In patients with mild dementia, EDS is greatest in DLB and comparably lower in bvFTD and AD.

https://journals.sagepub.com/doi/pdf/10.1177/1533317519828046

Michael H. Silber

Papers

Para-suicidal amnestic behavior associated with chronic zolpidem use: implications for patient safety.

The Investigation of Sleepiness

Adult-onset autosomal dominant leukodystrophy presenting with REM sleep behavior disorder

Amiodarone‐associated neuromyopathy: a report of four cases

Excessive Daytime Sleepiness in Major Dementia Syndromes