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

INTRODUCTION The clinical features of dementia with Lewy bodies (DLB) during wakefulness are well known. Other than rapid eye movement (REM) sleep behavior disorder, only limited data exists on other sleep disturbances and disorders in DLB. We sought to characterize the polysomnographic (PSG) findings in a series of DLB patients with sleep-related complaints. METHODS Retrospective study of patients with DLB who underwent clinical PSG at Mayo Clinic, Rochester or Mayo Clinic, Jacksonville over an almost 11-year span for evaluation of dream enactment behavior, excessive nocturnal movements, sleep apnea, hypersomnolence, or insomnia. The following variables were analyzed: respiratory disturbance index (RDI) in disordered breathing events/hour, periodic limb movement arousal index, arousals for no apparent reason (AFNAR), total arousal index, presence of REM sleep without atonia, and percent sleep efficiency. RESULTS Data on 78 patients (71 male, 7 female) were analyzed. The mean age was 71±8 years. Seventy-five (96%) patients had histories of recurrent dream enactment during sleep with 83% showing confirmation of REM sleep without atonia±dream enactment during PSG. Mean RDI=11.9±5.8, periodic limb movement arousal index =5.9±8.5, arousals for no apparent reason index=10.7±12.0, and total arousal index=26.6±17.4. Sleep efficiency was <80% in 72% of the sample, <70% in 49%, and <60% in 24%. In patients who did not show evidence of significant disordered breathing (23 with RDI<5), 62% of arousals were AFNARs. In those patients who had significant disordered breathing (55 with RDI≥5), 36% of arousals were AFNARs. Six patients underwent evaluations with PSG plus multiple sleep latency test. Two patients had mean initial sleep latencies of <5 minutes, and both had RDI<5. No patient had any sleep onset REM periods. Nineteen patients have undergone neuropathologic examination, and 18 have had limbic-predominant or neocortical-predominant Lewy body pathology. One had progressive supranuclear palsy, but no REM sleep was recorded in prior PSG. CONCLUSIONS In patients with DLB and sleep-related complaints, several sleep disturbances in addition to REM sleep behavior disorder are frequently present. In this sample, about 3/4 had a significant number of arousals not accounted for by a movement or breathing disturbance, and the primary sleep disorders do not seem to entirely account for the poor sleep efficiency in DLB, especially in those without a significant breathing disorder. Further studies are warranted to better understand the relationship between disturbed sleep, arousal, and DLB; such characterization may provide insights into potential avenues of treatment of symptoms that could impact quality of life.

/pdf/polysomnographic-findings-in-dementia-with-lewy-bodies-2yzs3sxiwx.pdf

Polysomnographic findings in dementia with Lewy bodies.

Study Objectives:This study involves a replication and extension of a previous one reported by Hurwitz et al (1991) on the treatment of certain parasomnias with hypnosis.Methods:Thirty-six patients...

The treatment of parasomnias with hypnosis: a 5-year follow-up study.

Comorbidities in a community sample of narcolepsy

Objective To describe a patient with diencephalic and mesencephalic presentation of a Ma1 and Ma2 antibody–associated paraneoplastic neurological disorder. Design Case report. Setting The Colorado Neurological Institute Movement Disorders Center in Englewood, Colorado, and the Mayo Clinic in Rochester, Minnesota. Patient A 55-year-old man with a paraneoplastic neurological disorder characterized by rapid eye movement sleep behavior disorder, narcolepsy, and a progressive supranuclear palsy–like syndrome in the setting of tonsillar carcinoma. Intervention Immunotherapy for paraneoplastic neurological disorder, surgery and radiotherapy for cancer, and symptomatic treatment for parkinsonism and sleep disorders. Main Outcome Measures Polysomnography, multiple sleep latency test, and neurological examination. Results The cancer was detected at a limited stage and treatable. After oncological therapy and immunotherapy, symptoms stabilized. Treatment with modafinil improved daytime somnolence. Conclusions Rapid onset and progression of multifocal deficits may be a clue to paraneoplastic etiology. Early treatment of a limited stage cancer (with or without immunotherapy) may possibly slow progression of neurological symptoms. Symptomatic treatment may be beneficial.

https://jamanetwork.com/journals/jamaneurology/articlepdf/802749/nob05039_521_524.pdf

Narcolepsy, REM sleep behavior disorder, and supranuclear gaze palsy associated with Ma1 and Ma2 antibodies and tonsillar carcinoma

Lewy body variant of Alzheimer's disease (AD) identified by postmortem ubiquitin staining in a previously reported case of AD associated with REM sleep behavior disorder.

Michael H. Silber

Papers

Polysomnographic findings in dementia with Lewy bodies.

The treatment of parasomnias with hypnosis: a 5-year follow-up study.

Comorbidities in a community sample of narcolepsy

Narcolepsy, REM sleep behavior disorder, and supranuclear gaze palsy associated with Ma1 and Ma2 antibodies and tonsillar carcinoma

Lewy body variant of Alzheimer's disease (AD) identified by postmortem ubiquitin staining in a previously reported case of AD associated with REM sleep behavior disorder.