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

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.

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

I read the article by Rowe et al.1 with interest. Diagnosing Alzheimer disease (AD) in a preclinical phase would enable early implementation of therapeutic interventions which might have long-term benefits.

PET technology by using the Pittsburgh compound (PiB) allows detection of amyloid deposits in the brain.1,2 Pathologic studies indicate that amyloid deposition is present in cortical regions of all patients with AD even before the onset of dementia.3 One application of PiB-PET may be all that is necessary to identify the neuropathologic changes of AD in clinically normal individuals prior to the development of cognitive changes. These individuals would be considered to have preclinical AD.

PET studies performed with PiB in cognitively intact subjects have shown that between 15 and 22% of them had abnormal scans.1,2 The objective is to determine who and when someone will become demented. It is and will be unclear because the proportion of subjects with cerebral amyloid deposits is, and will be, higher than the proportion of people with clinical AD.

Otherwise, it is impossible to understand pathologic observations which indicate that more than 30% of older persons over age 75 die without any clinical evidence of dementia despite showing amyloid deposits and pathologic changes characteristic of AD.3 Presumably all of them would have abnormal PiB-PET scans. Amyloid deposition is not synonymous with clinical AD unless we assume that everyone with an abnormal PiB-PET scan would develop AD.

Even in this case, many of them (70% according to pathologic data and prevalence estimates of AD) will die without dementia in the …

Imaging beta-amyloid burden in aging and dementia.

Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long-term hospitalization, misuse of medication, and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis, and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social, and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological, and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPSD.

/pdf/behavioral-and-psychological-symptoms-of-dementia-2h16hvl9b8.pdf

Behavioral and Psychological Symptoms of Dementia

Dementia with Lewy bodies is relatively common cause of degenerative dementia in older people. This debilitating disorder is comprised of core features including dementia, fluctuating cognition, motor parkinsonism, and visual hallucinations, as well as other symptoms such as rapid eye movement sleep behavior disorder, olfactory dysfunction, autonomic dysfunction, sensitivity to neuroleptics, anxiety, depression, and delusions. Pharmacotherapy, so far exclusively symptomatic, should be implemented with caution and only when symptoms are disturbing and after non-pharmacological interventions fail. Treatment with acetylcholinesterase inhibitors (AChEi), such as donepezil and rivastimine, is considered a first line therapy. There is substantial evidence that AChEi address cognitive as well as behavioral symptoms without substantially increasing parkinsonism. Dopaminergic treatment for motor symptoms requires balancing risk of worsened psychosis and is consider only moderately beneficial.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(03)00619-7.pdf

Dementia With Lewy Bodies

OBJECTIVE: This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies. METHOD: The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer’s Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer’s disease studied prospectively during life. RESULTS: The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy bod...

Catherine Joachim

Papers

Neuropathological Substrates of Psychiatric Symptoms in Prospectively Studied Patients With Autopsy-Confirmed Dementia With Lewy Bodies