Clinical Diagnostic Criteria for Dementia with Lewy Bodies

Diffuse Lewy body disease (DLBD)

Kosaka et al. [1], Dickson et al. [2], Lennox et al. [3]

Lewy body dementia (LBD)

Gibb et al. [4]

Lewy body variant of Alzheimer’s disease (LBVAD)

Hansen et al. [6], Förstl et al. [7]

Senile dementia of LB type (SDLT)

Perry et al. [8]

Dementia associated with cortical Lewy bodies (DCLB)

Byrne et al. [5]

Dementia with Lewy bodies (DLB)

McKeith et al. [9, 10]

Neurocognitive disorder with Lewy bodies (NCDLB)

APA [11]

Although the first case reports specifically describing patients with dementia and LBs appeared as early as 1961 when Okazaki reported on two elderly men presenting with cognitive decline and who subsequently developed severe rigidity [12], it was another two decades before Kosaka et al. [1] reported the first significant series of 34 cases, noting a 3:1 male predominance, with memory disturbance as the presenting feature in 67 %, psychotic states in 17 % and dizziness due to orthostatic hypotension in 17 %. Progressive dementia with muscular rigidity occurred eventually in 80 %, although only 25 % of cases were diagnosed with parkinsonism. The first substantial listing of these Japanese cases in the Western literature was in 1987 by Gibb et al. [4] who added four new UK cases. The following year, Burkhardt et al. [13] listed 34 additional cases from the USA and carried out a simple meta-analysis. The most common presentation was a “neurobehavioural syndrome”; memory impairment and other cognitive deficits were typical; all but one eventually becoming demented. Psychotic features such as depression, hallucinations and paranoia were seen in ten patients (29 %), two being psychotic for many years before developing other symptoms. Parkinsonian features, the most common of which was rigidity, were usually overshadowed by dementia; in only five cases (15 %) were no extrapyramidal features present. Duration of illness was very variable (1–20 years) with an end state of severe dementia, rigidity, akinetic mutism, quadriparesis in flexion and emaciation. The most common reported cause of death was aspiration pneumonia. Based upon these observations, Burkhardt et al. were the first to attempt a general description of the clinical syndrome associated with diffuse Lewy body disease, distinguishing it as separate from PD with dementia. They concluded that “DLBD (diffuse Lewy body disease) should be suspected in any elderly patient who presents with a rapidly progressive dementia, followed in short order by rigidity and other parkinsonian features. Myoclonus may be present”[13].

Crystal et al. [14] in a paper entitled “Antemortem diagnosis of diffuse Lewy body disease” criticised this approach on the grounds that “extrapyramidal features occur in many patients with severe AD and since dementia occurs in many subjects with PD, the clinical criteria for the diagnosis of DLBD remain unclear”. The authors proposed alternative criteria of “progressive dementia with gait disorder, psychiatric symptoms and a burst pattern on EEG at the time of moderate dementia”. No particular characteristics of the pattern of cognitive impairment were noted.

Although these early clinical definitions were important in drawing attention to the existence of DLBD and describing some of its salient characteristics, neither could be regarded as satisfactory for clinical diagnostic purposes, since they were not operationalised in a way which would allow acceptable inter-rater reliability [15]. Despite the emphasis on motor disability, these early attempts did make a clear distinction between the DLBD group and patients with PD who later developed dementia, a proposition which has been maintained in the DLB consensus criteria and which de facto has encouraged the development of diagnostic criteria for PD dementia along a separate but parallel path.

5.1.2 Development of Operationalised Criteria Based Upon Individual Cohorts

At around the same time that US investigators were reporting the cases above, the Nottingham, UK, group reported the clinical characteristics of 15 new cases in considerable detail, the largest single-site series published at that time [16] and which led to the first formal proposal of operationalised criteria for dementia associated with cortical Lewy bodies (DCLB) [5]. Seven were men, the mean age at onset was 72 years and the mean duration of illness 5.5 years. Forty per cent presented with symptoms and signs of idiopathic PD, with cognitive impairment occurring 1–4 years later. A further 20 % had parkinsonism and mild cognitive impairment at presentation, and the remaining 40 % showed motor features later in their illnesses, gait disturbance and postural abnormalities being most common. These latter cases presented with neuropsychiatric features only, in various combinations of cognitive impairment, paranoid delusions and visual or auditory hallucinations. Fourteen of the 15 were demented before death, the exception presenting with classical PD and later becoming depressed, irritable and mildly forgetful with frequent falls. Fluctuating cognition with episodic confusion for which no adequate underlying cause could be found was observed in 80 % of the Nottingham cases. Byrne also drew attention to the frequent occurrence of depression (20 %) and psychosis (33 %). In retrospect many of these cases would now be classified as having PD dementia rather than DLB.

Also around the same time, the Newcastle upon Tyne group identified 14 UK cases with the neuropathological features of “senile dementia of Lewy body type” (SDLT) [8] accounting for 15 % of a series of dementia autopsies. These SDLT cases had been regarded during lifetime as clinically atypical, “causing much diagnostic perplexity”. Acute onset, fluctuating course, more rapid deterioration, early and prominent hallucinatory and behavioural disturbances and associated mild parkinsonian features were present. Two further Newcastle series were reported soon after [17, 18], and depressive symptoms, unexplained falls, observed disturbances of consciousness and excessive sensitivity to side effects of neuroleptic medication were added to the list of clinical characteristics with potential to distinguish DLB pathology cases from AD.

Based upon these observations, new clinical diagnostic criteria proposed with an emphasis upon cognitive dysfunction and neuropsychiatric features which could occur in the absence of extrapyramidal motor signs, and an attempt was made to describe the typical course of illness. “The first stage is often recognised only in retrospect and may extend back 1–3 years pre-presentation with occasional minor episodes of forgetfulness, sometimes described as lapses of concentration or “switching off”. A brief period of delirium is sometimes noted for the first time, often associated with genuine physical illness and/or surgical procedures. Disturbed sleep, nightmares and daytime drowsiness often persist after recovery.

Progression to the second stage frequently prompts psychiatric or medical referral. A more sustained cognitive impairment is established, albeit with marked fluctuations in severity. Recurrent confusional episodes are accompanied by vivid hallucinatory experiences, visual misidentification syndromes and topographical disorientation. Extensive medical screening is usually negative. Attentional deficits are apparent as apathy, and daytime somnolence and sleep behaviour disorder may be severe. Gait disorder and bradykinesia are often overlooked, particularly in elderly subjects. Frequent falls occur due either to postural instability or syncope.

The third and final stage often begins with a sudden increase in behavioural disturbance, leading to requests for sedation or hospital admission by perplexed and exhausted carers. The natural course from this point is variable and obscured by the high incidence of adverse reactions to neuroleptic medication. For patients not receiving, or tolerating neuroleptics, a progressive decline into severe dementia with dysphasia and dyspraxia occurs over months or years, with death usually due to cardiac or pulmonary disease. During this terminal phase, patients show continuing behavioural disturbance including vocal and motor responses to hallucinatory phenomena. Lucid intervals with some retention of recent memory function and insight may still be apparent. Neurological disability is often profound with fixed flexion deformities of the neck and trunk and severe gait impairment” [17].

5.1.3 The Lewy Body Variant of Alzheimer’s Disease

The majority of case reports and series up till this time generally made reference to the atypical clinical presentations of patients with cortical LB pathology, who generally did not easily fit any of the existing diagnostic rubrics. Exceptions to this were the reports by Hansen et al. [6] working in San Diego and Förstl et al. [7] in London, both of which described patients who met clinical criteria for possible or probable Alzheimer’s disease (AD). The Förstl series comprised four men and four women who did not differ from autopsy-confirmed AD controls in survival time, severity of cognitive impairment or presence of hallucinations or fluctuation. Five of the eight were recorded as having confusional states and five also developed pronounced parkinsonism at a later stage. They concluded that the mere presence of LB in a case of dementia did not seem to warrant the differentiation of a separate illness, particularly as rigidity appeared to be the only characteristic clinical feature. They regarded their patients as having “Lewy body variant of Alzheimer’s disease (LBVAD)”, a term which had been coined by Hansen and colleagues a few years earlier. The San Diego group had been studying clinically diagnosed AD patients meeting NINCDS-ADRDA criteria but found that 13 of 36 such cases followed to autopsy had cortical and subcortical LBs in addition to pathologically confirmed AD.

The only differences between the LBVAD and pure AD cases were that the former had a different neuropsychological profile with more severe attentional deficits, reduced verbal fluency and severely impaired visuospatial performance on block design and drawing tests. Mild extrapyramidal features with masked facies, bradykinesia and gait difficulty were also recorded. Although Hansen et al. concluded that “in some case it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological profile”, they did not extend to generating formalised diagnostic criteria [6].

5.2 Development of International Consensus Criteria

By the early 1990s, it was becoming apparent that DLB was a relatively common cause of dementia in old age and that the several research groups investigating it were adopting different terminologies which were most likely predicated on their different patient sampling biases and the relatively small size of individual case series. All of the essential clinical diagnostic elements had been described by this stage, but it was unclear how to use the information to construct a set of clinically useful diagnostic guidelines or how to conceptualise relationships between the new atypical group with AD, LBVAD or PDD. The way forward was achieved through the DLB Consortium which established itself as a collaboration of interested researchers with international and multidisciplinary membership. An account of events leading up to and including the establishment of this group has previously been published [19]. The DLB Consortium also worked closely with the International Movement Disorder Society working groups which developed criteria for the clinical diagnosis of PD dementia [20, 21] and through a boundary exercise were able to ensure a harmonised diagnostic glossary (see Fig. 5.1) across these parts of the Lewy body disease spectrum [22].

Fig. 5.1

A simple schematic shows the relationship between the terms LBD, DLB and PDD. This simple and memorable scheme should be adhered to in order to ensure consistency in diagnostic practice. This is equally important to patients and their families as it is to clinicians and researchers

5.2.1 First Report of the DLB Consortium

The consortium on DLB met for the first time in October 1995 in Newcastle upon Tyne, to agree common clinical and pathological methods and nomenclature based upon the evidence and opinion available [9]. DLB was recommended as an appropriate, generic term for those previously used by different groups and “because it acknowledges the presence of LB without specifying their relative importance in symptom formation with respect to other degenerative or vascular pathology that is simultaneously present”. This seems to have been a sensible decision given subsequent advances in our understanding of α-synuclein pathology and neuritic/synaptic disruption in these patients. Lewy bodies per se are almost certainly not the cause of neuronal dysfunction and may indeed represent a neuroprotective response. Although much of the first consensus paper was devoted to describing pathological sampling and staining and scoring methods [9], it also described in some detail the particular characteristics of the cognitive impairments of DLB as differing from the dementia syndrome of AD, in which memory deficits predominate. In DLB, attentional deficits and prominent visuospatial dysfunction are the main features [23, 24], and amnestic deficits are often less evident, especially in the early stages. Probable DLB could be diagnosed according to this system (Table 5.2) if any two of the three key symptoms were present, namely, fluctuation, visual hallucinations or spontaneous motor features of parkinsonism, and possible DLB could be diagnosed if only one was present.

Table 5.2

Consensus criteria for the clinical diagnosis of probable and possible DLB – report of the first consortium meeting [9]

1. The central feature required for a diagnosis of DLB is progressive cognitive decline of sufficient magnitude to interfere with normal social and occupational function. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention and of frontal–subcortical skills and visuospatial ability may be especially prominent

2. Two of the following core features are essential for a diagnosis of probable DLB, and one is essential for possible DLB:

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