Functional and structural brain network correlates of visual hallucinations in Lewy body dementia.

Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology cases. Computational models propose that impairment of visual and attentional networks is aetiologically key to the manifestation of visual hallucinations symptomatology. However, there is still a lack of experimental evidence on functional and structural brain network abnormalities associated with visual hallucinations in Lewy body dementia. We used EEG source localization and network based statistics to assess differential topographical patterns in Lewy body dementia between 25 participants with visual hallucinations and 17 participants without hallucinations. Diffusion tensor imaging was used to assess structural connectivity between thalamus, basal forebrain and cortical regions belonging to the functionally affected network component in the hallucinating group, as assessed with network based statistics. The number of white matter streamlines within the cortex and between subcortical and cortical regions was compared between hallucinating and not hallucinating groups and correlated with average EEG source connectivity of the affected subnetwork. Moreover, modular organization of the EEG source network was obtained, compared between groups and tested for correlation with structural connectivity. Network analysis showed that compared to non-hallucinating patients, those with hallucinations feature consistent weakened connectivity within the visual ventral network, and between this network and default mode and ventral attentional networks, but not between or within attentional networks. The occipital lobe was the most functionally disconnected region. Structural analysis yielded significantly affected white matter streamlines connecting the cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating compared to not hallucinating patients. The number of streamlines in the tract between the basal forebrain and the cortex correlated with cortical functional connectivity in non-hallucinating patients, while a correlation emerged for the white matter streamlines connecting the functionally affected cortical regions in the hallucinating group. This study proposes, for the first time, differential functional networks between hallucinating and not hallucinating Lewy body dementia patients, and provides empirical evidence for existing models of visual hallucinations. Specifically, the outcome of the present study shows that the hallucinating condition is associated with functional network segregation in Lewy body dementia and supports the involvement of the cholinergic system as proposed in the current literature.

Weighted network measures reveal differences between dementia types: An EEG study.

The diagnosis of dementia with Lewy bodies (DLB) versus Alzheimer's disease (AD) can be difficult especially early in the disease process. However, one inexpensive and non-invasive biomarker which could help is electroencephalography (EEG). Previous studies have shown that the brain network architecture assessed by EEG is altered in AD patients compared with age-matched healthy control people (HC). However, similar studies in Lewy body diseases, that is, DLB and Parkinson's disease dementia (PDD) are still lacking. In this work, we (a) compared brain network connectivity patterns across conditions, AD, DLB and PDD, in order to infer EEG network biomarkers that differentiate between these conditions, and (b) tested whether opting for weighted matrices led to more reliable results by better preserving the topology of the network. Our results indicate that dementia groups present with reduced connectivity in the EEG α band, whereas DLB shows weaker posterior-anterior patterns within the ß-band and greater network segregation within the θ-band compared with AD. Weighted network measures were more consistent across global thresholding levels, and the network properties reflected reduction in connectivity strength in the dementia groups. In conclusion, ß- and θ-band network measures may be suitable as biomarkers for discriminating DLB from AD, whereas the α-band network is similarly affected in DLB and PDD compared with HC. These variations may reflect the impairment of attentional networks in Parkinsonian diseases such as DLB and PDD.

Neural correlates of attention-executive dysfunction in lewy body dementia and Alzheimer's disease.

Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto-parieto-occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention-executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases.

Support and information needs following a diagnosis of dementia with Lewy bodies.

BACKGROUND: There is a lack of knowledge regarding the information and support needs of people with dementia with Lewy bodies (DLB) and their families around the time of diagnosis. METHODS: A volunteer sample of patients with DLB and their family members completed a web survey hosted by the UK based Lewy Body Society in May 2014. This focused on past experiences of information and support received and what information and support needs would have been beneficial at the time of diagnosis. RESULTS: One hundred and twenty five adults responded to the survey. The majority were first degree relatives or spouses of people with DLB (n = 107, 86%). Approximately 50% (n = 61) reported they had not received any tangible support at diagnosis. Thirteen categories of information needs were identified. CONCLUSIONS: People with DLB and their family members are currently inadequately supported at diagnosis. There is a need to address information needs related to symptomology, medication and prognosis, including provision of emotional and instrumental social support. Seeking the views of recipients of information and support is important in ensuring relevance and appropriateness prior to the development of interventions to improve the knowledge and coping skills of people with DLB and caregivers.

Patient and Informant Views on Visual Hallucinations in Parkinson Disease.

OBJECTIVE: Visual hallucinations (VHs) are a very personal experience, and it is not clear whether information about them is best provided by informants or patients. Some patients may not share their hallucinatory experiences with caregivers to avoid distress or for fear of being labeled insane, and others do not have informants at all, which limits the use of informant-based questionnaires. The aim of this study was to compare patient and caregiver views about VHs in Parkinson disease (PD), using the North-East Visual Hallucinations Interview (NEVHI). METHODS: Fifty-nine PD patient-informant pairs were included. PD patients and informants were interviewed separately about VHs using the NEVHI. Informants were additionally interviewed using the four-item version of the Neuropsychiatric Inventory. Inter-reliability and concurrent validity of the different measures were compared. RESULTS: VHs were more commonly reported by patients than informants. The inter-rater agreement between NEVHI-patient and NEVHI-informant was moderate for complex VHs (Cohen's kappa = 0.44; 95% confidence interval [CI]: 0.13-0.75; t = 3.43, df = 58, p = 0.001) and feeling of presence (Cohen's kappa = 0.35; 95% CI: 0.00-0.70; t = 2.75, df = 58, p = 0.006), but agreement was poor for illusions (Cohen's kappa = 0.25; 95% CI: -0.07-0.57; t = 2.36, df = 58, p = 0.018) and passage hallucinations (Cohen's kappa = 0.16; 95% CI: -0.04-0.36; t = 2.26, df = 58, p = 0.024). CONCLUSION: When assessing VHs in PD patients, it is best to rely on patient information, because not all patients share the details of their hallucinations with their caregivers.

The assessment of cognition in visually impaired older adults.

BACKGROUND: visual and cognitive impairments are common in later life. Yet there are very few cognitive screening tests for the visually impaired. OBJECTIVE: to screen for cognitive impairment in the visually impaired. METHODS: case-control study including 150 elderly participants with visual impairment (n = 74) and a control group without visual impairment (n = 76) using vision-independent cognitive tests and cognitive screening tests (MMSE and clock drawing tests (CDT)) which are in part vision dependent. RESULTS: the scoring of the two groups did not differ in the vision-independent cognitive tests. Visually impaired patients performed poorer than controls in the vision-dependent items of the MMSE (T = 7.3; df: 148; P < 0.001) and in CDT (T = 3.1; df: 145; P = 0.003). No group difference was found when vision-independent items were added to MMSE and CDT. The test score gain by the use of vision-independent items correlated with the severity of visual impairment (P < 0.002). CONCLUSION: visually impaired patients benefit from cognitive tests, which do not rely on vision. The more visually impaired the greater the benefit.

The feasibility and acceptability of a psychosocial intervention to support people with dementia with Lewy bodies and family care partners.

OBJECTIVES: Psychosocial support for people with dementia with Lewy bodies (DLB) and family care partners is frequently lacking, despite the need expressed by those with lived experience. Our objective was to examine the feasibility and acceptability of an intervention designed to build coping capability. DESIGN: The design was non-randomised with all participants receiving the intervention. SETTING: The setting was a Memory Assessment and Management Service in the Northeast of England. PARTICIPANTS: Participants comprised 19 dyads consisting of a person with DLB and a family care partner. INTERVENTION: The intervention was group-based, with weekly sessions attended for up to four successive weeks. It was informed by Social Cognitive Theory. MEASUREMENTS: Data were collected on recruitment, attendance and attrition, self-efficacy, mood, stress and participant experience. RESULTS: Recruitment was achieved with minimal attrition and three successive groups were delivered. Care partners felt more in control and able to cope in at least 3 of 13 areas with 73% feeling this way in eight or more areas. Three themes were identified from post-intervention interviews: people like us, outcomes from being a group member and intervention design. CONCLUSIONS: A DLB-specific group intervention is acceptable to people with DLB and family care partners, and recruitment is feasible within a specialist service. Participation may enhance understanding of this condition and reduce social isolation. It may improve care partners' coping capability particularly if targeted towards those with low prior understanding of DLB and more stress. Means of evaluating outcomes for people with DLB need further development.

Exploring Bottom-Up Visual Processing and Visual Hallucinations in Parkinson's Disease With Dementia.

Visual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls (n = 21) and PDD patients (n = 34) with a range of VH severities. PDD patients showed increased N2 latency relative to controls, but no significant differences in VEP measures were found for patients reporting complex VH (CVH) (n = 17) compared to those without VH. Our VEP findings support previous reports of declining visual system physiology in PDD and some evidence of visual system differences between patients with and without VH. However, we did not replicate previous findings of a major relationship s between the integrity of the visual pathway and VH.

Electroencephalographic derived network differences in Lewy body dementia compared to Alzheimer's disease patients.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) require differential management despite presenting with symptomatic overlap. Currently, there is a need of inexpensive DLB biomarkers which can be fulfilled by electroencephalography (EEG). In this regard, an established electrophysiological difference in DLB is a decrease of dominant frequency (DF)-the frequency with the highest signal power between 4 and 15 Hz. Here, we investigated network connectivity in EEG signals acquired from DLB patients, and whether these networks were able to differentiate DLB from healthy controls (HCs) and associated dementias. We analysed EEG recordings from old adults: HCs, AD, DLB and Parkinson's disease dementia (PDD) patients. Brain networks were assessed with the minimum spanning tree (MST) within six EEG bands: delta, theta, high-theta, alpha, beta and DF. Patients showed lower alpha band connectivity and lower DF than HCs. DLB and PDD showed a randomised MST compared with HCs and AD in high-theta and alpha but not in DF. The MST randomisation in DLB and PDD reflects decreased brain efficiency as well as impaired neural synchronisation. However, the lack of network topology differences at the DF between all dementia groups and HCs may indicate a compensatory response of the brain to the neuropathology.

Reduced occipital GABA in Parkinson disease with visual hallucinations.

OBJECTIVE: To investigate the relationship between visual hallucinations in Parkinson disease (PD) and levels of γ-aminobutyric acid (GABA) in the primary visual cortex. METHODS: We utilized magnetic resonance spectroscopy to investigate occipital GABA levels in 36 participants with PD, 19 with and 17 without complex visual hallucinations, together with 20 healthy controls without hallucinations. In addition, we acquired T1-weighted MRI, whole-brain fMRI during a visual task, and diffusion tensor imaging. RESULTS: We found lower GABA+/creatine in PD with visual hallucinations (0.091 ± 0.010) vs those without (0.101 ± 0.010) and controls (0.099 ± 0.010) (F2,49 = 4.5; p = 0.016). Reduced gray matter in the hallucinations group was also observed in the anterior temporal lobe. Although there were widespread reductions in white matter integrity in the visual hallucinations group, this was no longer significant after controlling for cognitive function. CONCLUSIONS: The data suggest that reduced levels of GABA are associated with visual hallucinations in PD and implicate changes to the ventral visual stream in the genesis of visual hallucinations. Modulation of visual cortical excitability through, for example, pharmacologic intervention, may be a promising treatment avenue to explore.

Quantitative electroencephalography as a marker of cognitive fluctuations in dementia with Lewy bodies and an aid to differential diagnosis.

OBJECTIVE: We investigated for quantitative EEG (QEEG) differences between Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) patients and healthy controls, and for QEEG signatures of cognitive fluctuations (CFs) in DLB. METHODS: We analysed eyes-closed, resting state EEGs from 18 AD, 17 DLB and 17 PDD patients with mild dementia, and 21 age-matched controls. Measures included spectral power, dominant frequency (DF), frequency prevalence (FP), and temporal DF variability (DFV), within defined EEG frequency bands and cortical regions. RESULTS: DLB and PDD patients showed a leftward shift in the power spectrum and DF. AD patients showed greater DFV compared to the other groups. In DLB patients only, greater DFV and EEG slowing were correlated with CFs, measured by the clinician assessment of fluctuations (CAF) scale. The diagnostic accuracy of the QEEG measures was 94% (90.4-97.9%), with 92.26% (80.4-100%) sensitivity and 83.3% (73.6-93%) specificity. CONCLUSION: Although greater DFV was only shown in the AD group, within the DLB group a positive DFV - CF correlation was found. QEEG measures could classify DLB and AD patients with high sensitivity and specificity. SIGNIFICANCE: The findings add to an expanding literature suggesting that EEG is a viable diagnostic and symptom biomarker in dementia, particularly DLB.

Structural Brain Correlates of Attention Dysfunction in Lewy Body Dementias and Alzheimer's Disease.

Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of dementia that have different clinical profiles but are both commonly associated with attentional deficits. The aim of this study was to investigate efficiency of different attentional systems in LBD and AD and its association with brain structural abnormalities. We studied reaction time (RT) data from 45 LBD, 31 AD patients and 22 healthy controls (HCs) using the Attention Network Test (ANT) to assess the efficiency of three different attentional systems: alerting, orienting and executive conflict. Voxel-based morphometry (VBM) was used to investigate relations between different attention components and cortical volume. Both dementia groups showed slower overall RTs than controls, with additional slowing in LBD relative to AD. There was a significant alerting effect in controls which was absent in the dementia groups, the executive conflict effect was greater in both dementia groups compared to controls, but the orienting effect did not differ between groups. Mean RT in AD was negatively correlated with occipital gray matter (GM) volume and in LBD orienting efficiency was negatively related to occipital white matter (WM) volume. Given that previous studies in less impaired patients suggest a maintenance of the alerting effect, the absent alerting effect in our study suggests a loss of alerting efficiency with dementia progression. While orienting was largely preserved, it might be related to occipital structural abnormalities in LBD. Executive function was markedly impaired in both dementia groups, however, the absence of relations to brain volume suggests that it might be more related to functional rather than macrostructural pathophysiological changes.

Visual complaints and visual hallucinations in Parkinson's disease.

BACKGROUND: Visual symptoms are common in Parkinson's disease (PD) and are frequently under-diagnosed. The detection of visual symptoms is important for differential diagnosis and patient management. AIM: To establish the prevalence of recurrent visual complaints (RVC) and recurrent visual hallucinations (RVH) and to investigate their interaction in PD patients and controls. METHODS: This cross-sectional study included 88 PD patients and 90 controls. RVC and RVH were assessed with a visual symptom questionnaire and the North-East-Visual-Hallucinations-Interview (NEVHI). RESULTS: Double vision (PD vs. CONTROLS: 18.2% vs. 1.3%; p < 0.001), misjudging objects when walking (PD vs. CONTROLS: 12.5% vs. 1.3%; p < 0.01), words moving whilst reading (PD vs. CONTROLS: 17.0% vs. 1.3%; p < 0.001) and freezing in narrow spaces (PD vs. CONTROLS: 30.7% vs. 0%; p < 0.001) were almost exclusively found in PD patients. The same was true for recurrent complex visual hallucinations and illusions (PD vs. CONTROLS: both 17.0% vs. 0%; p < 0.001). Multiple RVC (43.2% vs. 15.8%) and multiple RVH (29.5% vs. 5.6%) were also more common in PD patients (both p < 0.001). RVC did not predict recurrent complex visual hallucinations; but double vision (p = 0.018, R(2) = 0.302) and misjudging objects (p = 0.002, R(2) = 0.302) predicted passage hallucinations. Misjudging objects also predicted the feeling of presence (p = 0.010, R(2) = 0.321). CONCLUSIONS: Multiple and recurrent visual symptoms are common in PD. RVC emerged as risk factors predictive of the minor forms of hallucinations, but not recurrent complex visual hallucinations.

A semi-structured interview to assess visual hallucinations in older people.

OBJECTIVE: Visual hallucinations are under-reported by patients and are often undiscovered by health professionals. There is no gold standard available to assess hallucinations. Our objective was to develop a reliable, valid, semi-structured interview for identifying and assessing visual hallucinations in older people with eye disease and cognitive impairment. METHODS: We piloted the North-East Visual Hallucinations Interview (NEVHI) in 80 older people with visual and/or cognitive impairment (patient group) and 34 older people without known risks of hallucinations (control group). The informants of 11 patients were interviewed separately. We established face validity, content validity, criterion validity, inter-rater agreement and the internal consistency of the NEVHI, and assessed the factor structure for questions evaluating emotions, cognitions, and behaviours associated with hallucinations. RESULTS: Recurrent visual hallucinations were common in the patient group (68.8%) and absent in controls (0%). The criterion, face and content validities were good and the internal consistency of screening questions for hallucinations was high (Cronbach alpha: 0.71). The inter-rater agreements for simple and complex hallucinations were good (Kappa 0.72 and 0.83, respectively). Four factors associated with experiencing hallucinations (perceived control, pleasantness, distress and awareness) were identified and explained a total variance of 73%. Informants gave more 'don't know answers' than patients throughout the interview (p = 0.008), especially to questions evaluating cognitions and emotions associated with hallucinations (p = 0.02). CONCLUSIONS: NEVHI is a comprehensive assessment tool, helpful to identify the presence of visual hallucinations and to quantify cognitions, emotions and behaviours associated with hallucinations.