J. L. Cummings

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

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.

Diagnostic Procedures for Parkinson's Disease Dementia : Recommendations from the Movement Disorder Society Task Force

A preceding article described the clinical features of Parkinsons disease dementia (PD‐D) and proposed clinical diagnostic criteria for “probable” and “possible” PD‐D. The main focus of this article is to operationalize the diagnosis of PD‐D and to propose pratical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time‐consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD‐D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD‐D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence‐based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.

Diagnostic criteria for psychosis in Parkinson's disease: Report of an NINDS, NIMH work group

There are no standardized diagnostic criteria for psychosis associated with Parkinsons disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we propose provisional criteria for PDPsy in the style of the Diagnostic and Statistical Manual of Mental Disorders IV‐TR. PDPsy has a well‐characterized temporal and clinical profile of hallucinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psychosis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinsons disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospatial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxication. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic criteria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and contain descriptions of the full range of characteristic symptoms, chronology of onset, duration of symptoms, exclusionary diagnoses, and associated features such as dementia. These criteria require validation and may be refined, but form a starting point for studies of the epidemiology and pathophysiology of PDPsy, and are a potential indication for therapy development.

A study of the Lund‐Manchester research criteria for frontotemporal dementia Clinical and single‐photon emission CT correlations

We evaluated the Lund-Manchester research criteria (LMRC) for frontotemporal dementia (FTD). With single-photon emission CT, we diagnosed 30 patients with FTD. These patients were compared with 30 with a research diagnosis of Alzheimers disease (AD). We scored every patient on each LMRC item and compared the two groups. A discriminant function showed that loss of personal awareness, hyperorality, stereotyped and perseverative behavior, progressive reduction of speech, and preserved spatial orientation differentiated 100% of FTD and AD subjects. Items relating to affect and physical findings were not different in FTD versus AD. Loss of personal awareness, eating, perseverative behavior, and reduction of speech are the LMRC items that most clearly differentiate FTD from AD.

A quantitative MRI study of vascular dementia

We studied the MRI and clinical factors associated with dementia following stroke by quantifying ventricle-to-brain ratio (VBR), anatomic region of infarction, and cortical, subcortical, and white matter areas of infarction in 24 stroke patients with dementia and 29 nondemented stroke patients. The factors that most strongly correlated with dementia were total white matter lesion (WML) area, left WML, VBR, right WML, age, left cortical infarction area, left parietal infarction area, and total infarction area. Using discriminant analysis, these factors correctly classified 28 of 29 nondemented patients and 18 of 24 demented patients. Both cortical and white matter total infarction area measurements were strongly associated with dementia in stroke patients, suggesting that these factors strongly influenced the development of dementia following stroke. There was a strong association between dementia and left but not right-hemisphere infarction area. The only demographic factor that strongly associated with dementia was age.

Alzheimer's disease and Parkinson's disease Comparison of speech and language alterations

Speech and language alterations were assessed in 51 patients with Parkinsons disease (PD) and 10 patients with dementia of the Alzheimer type (DAT). Thirty-five of the PD patients had no evidence of intellectual impairment on a conventional mental status questionnaire and 16 of the PD patients had dementia syndromes of comparable severity to the DAT patients. DAT produced significantly greater language disturbances, including anomia, decreased information content of spontaneous speech, and diminished word list generation. PD patients had significantly decreased phrase length, impaired speech melody, dysarthria, and agraphia. The results suggest that the dementia of PD is distinguishable from that of DAT: PD patients have prominent motor speech abnormalities, whereas DAT patients exhibit more profound language alterations.

Speech and language alterations in multi‐infarct dementia

Speech and language functions were assessed in 18 patients with multi-infarct dementia (MID) and 14 with dementia of the Alzheimer type (DAT). The age range and dementia severity of the two groups were comparable. We used a speech and language battery assessing 37 elements of verbal output to characterize alterations in the patients. MID patients had more abnormalities of motor aspects of speech, whereas DAT patients had empty speech, more marked anomia, and relative sparing of motor speech functions. The results demonstrate that speech and language differ in MID and DAT. In addition, MID patients exhibited common clinical features despite the heterogeneity of the syndrome.

ADCS Prevention Instrument Project: overview and initial results.

One objective of the Alzheimers Disease Cooperative Study (ADCS) is to develop new or improved instruments and assessment methods for evaluating treatment efficacy in Alzheimer disease (AD) clinical trials. The ADCS Instrument Committee has previously helped to define the state of the art in assessment for AD and Mild Cognitive Impairment clinical trials. We are now entering an exciting era of primary prevention trials to evaluate promising treatments that may delay disease onset and there is a need to develop appropriate instruments for these trials. The ADCS instrument committee has undertaken a project to develop instruments for prevention studies that assess domains known to be important in AD. Prevention trials are long and require large numbers of subjects, making them costly and requiring a high burden of participation for subjects. The current study focused on developing instruments that can be completed at home and in the clinic. The instruments are being evaluated in a cohort of nondemented elderly participating in a 4-year longitudinal study that simulates the design of a primary prevention trial. This report describes the design, baseline characteristics, and some longitudinal outcomes of the study cohort through the completion of the first 2 years of follow-up. We also describe the assessment domains to be measured with our new experimental instruments. This study recruited 644 subjects, 75 years of age and older. Participation in a “book club” that provided free books of interest to elders was offered as a recruitment incentive. Approximately 23% had some mild cognitive symptoms consistent with a Clinical Dementia Rating of 0.5. All subjects received a standardized in-clinic evaluation at baseline, which is repeated annually for 4 years to identify cases suspected of developing dementia and to measure longitudinal change on established clinical assessments. Subjects completed a set of self-administered experimental instruments at home or in the clinic designed to assess cognitive function and behavior, global change, activities of daily living, quality of life, and resource use. An additional “mail-in cognitive function questionnaire” was obtained separately by mail, 1 month before the other assessments. To evaluate the feasibility, efficiency, and validity of the home-based instruments in comparison with acquiring the same information during a clinic visit, subjects were randomized to 1 of 2 conditions in which the baseline and annual follow-up assessments are completed either at home (“home group”) or at the study site during their clinic visits (“clinic group”). This initial report describes the ongoing 4-year longitudinal study and provides baseline results, which confirm the feasibility of obtaining home-based clinical information via mail or telephone. Initial results for the experimental instruments and for the book club are reported in separate accompanying articles.

Multiple system atrophy presenting with language impairment

Multiple system atrophy (MSA) typically presents with parkinsonism, cerebellar ataxia, corticospinal dysfunction, and autonomic failure.1 We describe a case of pathologically confirmed MSA with semantic language impairment. A 55-year-old right-handed psychiatrist presented with language difficulties since age 50. He had shrinking vocabulary, spelling, and reading difficulties, loss of foreign language skills, and difficulty with comprehension of complex conversations. His speech was fluent, grammatically correct, with occasional anomic pauses and substitution of low-frequency words with general words (e.g., “thing” and “it”). He had hyperreflexia in the right arm and leg, right-sided Babinski, writers cramp, and mildly impaired fine motor skills in the right hand. Neuropsychological evaluation revealed anomia (Boston Naming Test [BNT] score 35/60, <1%), intact verbal fluency (FAS 88%), surface dysgraphia (“curteus” instead of “courteous,” “medeval” instead of “medieval”), surface dyslexia (could not read “subtlety”), and moderate retrieval-type verbal memory deficit. His receptive vocabulary skills were below expectation given his advanced education (Peabody Picture Vocabulary Test, 48%). His performance …