Clinical Criteria for DLB

The presentation of DLB is usually one of both cortical and subcortical cognitive symptoms and signs, with worse visuospatial, executive and attentional dysfunction than is usually seen in AD. In the clinical series of Farina et al. [3], cognitive disturbances were reported at onset in 49% of their sample of 102 patients. Molano et al. [4] described memory loss in three of their eight mild cognitive impairment (MCI) patients of the DLB type (all eight of these MCI cases eventually had autopsy verification of their DLB). The other five cases had non-amnestic MCI (attention and executive problems were the most common early cognitive complaints). All of their patients had exhibited MCI complaints for 1–3 years before they met criteria for dementia, and they displayed the four associated symptoms of (1) REM sleep disorder, (2) parkinsonism, (3) visual hallucinations, and/or (4) fluctuations in attention. According to the fourth consensus report of the Dementia with Lewy Bodies Consortium, these four symptoms (besides dementia) are now considered to be the core clinical features of DLB [5]. Two or more of these four core features need to be present in order to make the diagnosis of probable DLB.

Diagnosis of Dementia

Dementia is defined as a decline in cognitive function of sufficient severity to impair one’s usual daily activities [5]. The severity of cognitive impairment can be assessed in the clinic with screening tests such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment [6, 7]. Functional status can be evaluated with the Lawton-Brody Instrumental Activities of Daily Living (IADL) Scale or the Performance Assessment of Self-Care Skills [8]. Besides memory loss, the three cognitive domains most likely to be affected in early DLB are attention, visuospatial function and executive function [2, 4]. Cagnin et al. [9] compared DLB and AD patients and found that DLB patients showed poorer performance on the pentagon copying test and slower speeds on various visual processing tasks.

Other DLB Symptoms

There are other clinical features that distinguish DLB from AD. For example, DLB patients have been shown to be uniquely sensitive to neuroleptic drugs, since they are more likely to develop the neuroleptic malignant syndrome (NMS) in response to typical antipsychotic agents, such as haloperidol, or high-potency atypical agents, such as olanzapine [2, 10]. NMS is a hyperthermia syndrome that can be associated with worsening of signs of parkinsonism and rhabdomyolysis. Other symptoms of DLB include orthostatic hypotension, systematized delusions, excessive daytime sedation, anxiety, and depression [5]. DLB should be diagnosed when dementia precedes or appears concurrently with parkinsonism. If a patient with PD develops dementia a year or more after the onset of the parkinsonism, then this is called PDD.

Imaging Diagnosis of DLB

During the MCI stages of both MCI-DLB and amnestic MCI, hippocampal measurements on volumetric magnetic resonance imaging (MRI) scans show that the volumes are still within the normal range [11]. Once dementia develops in these two patient populations, differences appear in hippocampal volumes: atrophy becomes more evident in those with AD, while volumes are more likely to remain in the normal range in DLB patients [11]. Hippocampal volumes may eventually become reduced over time in the DLB group, but at a much slower rate compared to that seen in AD. Complicating the diagnosis of DLB is the fact that most DLB cases also have concurrent AD changes at autopsy [12,13,14]. Sagittal views of volumetric MRI scans have demonstrated one feature that is similar in both DLB and AD patients: 25% atrophy in the basal forebrain [15]. Since many DLB patients exhibit poor visuospatial function, it is not surprising that perfusion single-photon emission computed tomography (SPECT) scans of DLB patients sometimes show reduced occipital perfusion, whereas occipital perfusion in AD patients is usually normal [16]. In both AD and DLB, there is usually reduced perfusion in both temporal and parietal lobes on perfusion SPECT images. Graff-Radford et al. [17] reported that DLB patients often have a unique sign on fluorodeoxyglucose positron-emission tomography (FDG-PET) called the “cingulate island sign,” which means that there is higher glucose metabolism in the posterior cingulate, compared to that which is seen in AD patients. By contrast, in early AD, there is reduced metabolism in the posterior cingulate [18]. When perfusion SPECT and FDG-PET scans were compared for their sensitivity and specificity in distinguishing AD from DLB, FDG-PET scans were found to be superior [19]. Amyloid PET imaging, which has shown increased beta-amyloid deposition in 68% of DLB patients, is not particularly useful in distinguishing AD from DLB patients, since both have significant amounts of amyloid deposits [20]. Dopamine transporter (DAT) scans are positive in both PD and DLB patients, but they can be helpful in distinguishing DLB from AD patients [5].