[Comparaison du déclin fonctionnel entre des patients atteints de démence à corps de Lewy et de la maladie d'Alzheimer]. / Functional decline in Lewy body dementia compared to Alzheimer disease.

Lewy body dementia (LBD) is the second most frequent neurodegenerative disorder after Alzheimer disease (AD). In this study, we compared functional decline between LBD and AD patients, considering motor dysfunction, over an 18-month follow-up period. We included all patients >70 years of age, with initial MMSE ≥ 20 and a diagnosis of possible or probable LBD or AD, who consulted at the memory centre of the Pitié-Salpêtrière hospital. Statistical analyses were performed using univariate tests and multivariate linear regression. Thirty-seven AD and 36 LBD patients were included, with a median age of 81 and a median MMSE score of 24/30. Global ADL Katz score decreased significantly for LBD people, compared to AD patients: -0.40 ± 0.75 versus 0 ± 0.24; p=0.003. Global IADL score decreased in the two populations but without a significant difference between the two groups: -1.71 ± 2.19 in LBD versus -1.32 (± 1.55); p=0.38. This study shows a significant decrease in autonomy in LBD patients over time that was faster than that in AD patients, related, in particular, to bathing, dressing and personal care.

Dementia with Lewy bodies and gait neural basis: a cross-sectional study.

BACKGROUND: Dementia with Lewy Bodies (DLB) is responsible for cognitive-behavioural disorders but also for gait disorders. The latter are thought to be related to parkinsonism, but the neural bases of these disorders are not well known, especially in the early stages. The aim of this study was to investigate by volumetric Magnetic Resonance Imaging the neuronal basis of gait disorders in DLB patients, compared to Healthy Elderly Controls and Alzheimer's Disease patients. METHODS: Clinical examination with motor assessment including 10-meter walking speed, one-leg balance and Timed Up and Go test, a comprehensive neuropsychological evaluation and 3D brain Magnetic Resonance Imaging were performed on 84 DLB patients, 39 Alzheimer's Disease patients and 22 Healthy Elderly Controls. We used Statistical Parametric Mapping 12 to perform a one-sample t-test to investigate the correlation between each gait score and gray matter volume (P ≤ 0.05 corrected for family-wise error). RESULTS: We found a correlation for DLB patients between walking speed and gray matter decrease (P < 0.05, corrected for family-wise error) in caudate nuclei, anterior cingulate cortex, mid-cingulate cortex, hippocampi, supplementary motor area, right cerebellar cortex and left parietal operculum. We found no correlation with Timed Up and Go test and one-leg balance. CONCLUSION: Gait disorders are underpinned by certain classical regions such as the cerebellum and the supplementary motor area. Our results suggest there may be a motivational and emotional component of voluntary gait in DLB subjects, underpinned by the cingulate cortex, a spatial orientation component, underpinned by hippocampi and suggest the involvement of brain processing speed and parkinsonism, underpinned by the caudate nuclei. TRIAL REGISTRATION: The study protocol has been registered on ClinicalTrials.gov. (NCT01876459) on June 12, 2013.

Neuropsychological and neuroanatomical underpinnings of the face pareidolia errors on the noise pareidolia test in patients with mild cognitive impairment and dementia due to Lewy bodies.

OBJECTIVE: Prior research on the Noise Pareidolia Test (NPT) has demonstrated its clinical utility in detecting patients with mild cognitive impairment and dementia due to Lewy Body Disease (LBD). However, few studies to date have investigated the neuropsychological factors underlying pareidolia errors on the NPT across the clinical spectrum of LBD. Furthermore, to our knowledge, no research has examined the relationship between cortical thickness using MRI data and NPT subscores. As such, this study sought to explore the neuropsychological and neuroanatomical factors influencing performance on the NPT utilizing the National Alzheimer's Coordinating Center Lewy Body Dementia Module. METHODS: Our sample included participants with normal cognition (NC; n = 56), LBD with mild cognitive impairment (LBD-MCI; n = 97), and LBD with dementia (LBD-Dementia; n = 94). Archival data from NACC were retrospectively analyzed for group differences in neuropsychological test scores and cognitive and psychiatric predictors of NPT scores. Clinicoradiological correlates between NPT subscores and a small subsample of the above LBD participants were also examined. RESULTS: Analyses revealed significant differences in NPT scores among groups. Regression analysis demonstrated that dementia severity, attention, and visuospatial processing contributed approximately 24% of NPT performance in LBD groups. Clinicoradiological analysis suggests a potential contribution of the right fusiform gyrus, but not the inferior occipital gyrus, to NPT pareidolia error scores. CONCLUSIONS: Our findings highlight the interplay of attention and visuoperceptual functions in complex pareidolia in LBD. Further investigation is needed to refine the utility of NPT scores in clinical settings, including identifying patients at risk for visual illusions and hallucinations.

Visual dysfunction in dementia with Lewy bodies.

PURPOSE OF REVIEW: To review the literature on visual dysfunction in dementia with Lewy bodies (DLB), including its mechanisms and clinical implications. RECENT FINDINGS: Recent studies have explored novel aspects of visual dysfunction in DLB, including visual texture agnosia, mental rotation of 3-dimensional drawn objects, and reading fragmented letters. Recent studies have shown parietal and occipital hypoperfusion correlating with impaired visuoconstruction performance. While visual dysfunction in clinically manifest DLB is well recognized, recent work has focused on prodromal or mild cognitive impairment (MCI) due to Lewy body pathology with mixed results. Advances in retinal imaging have recently led to the identification of abnormalities such as parafoveal thinning in DLB. Patients with DLB experience impairment in color perception, form and object identification, space and motion perception, visuoconstruction tasks, and illusions in association with visual cortex and network dysfunction. These symptoms are associated with visual hallucinations, driving impairment, falls, and other negative outcomes.

Distinct grey and white matter changes are associated with the phenomenology of visual hallucinations in Lewy Body Disease.

Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.

High pulse wave velocity is associated with enlarged perivascular spaces in dementia with Lewy bodies.

Previous studies have demonstrated associations between enlarged perivascular spaces (EPVS) and dementias such as Alzheimer's disease. However, an association between EPVS and dementia with Lewy bodies (DLB) has not yet been clarified. We performed a cross-sectional analysis of our prospective study cohort of 109 participants (16 with DLB). We assessed cognitive function, pulse wave velocity (PWV), and brain magnetic resonance imaging features. The relationships between EPVS and DLB were evaluated using multivariable logistic regression analyses. Compared with the non-dementia group, the DLB group was more likely to have EPVS in the basal ganglia. Compared with participants without EPVS, those with EPVS were older and had cognitive impairment and high PWV. In multivariable analyses, EPVS in the basal ganglia was independently associated with DLB. High PWV was also independently associated with EPVS in both the basal ganglia and centrum semiovale. High PWV may cause cerebrovascular pulsatility, leading to accelerated EPVS in DLB participants.

Advanced qEEG analyses discriminate between dementia subtypes.

BACKGROUND: Dementia is caused by neurodegenerative conditions and characterized by cognitive decline. Diagnostic accuracy for dementia subtypes, such as Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease with dementia (PDD), remains challenging. METHODS: Here, different methods of quantitative electroencephalography (qEEG) analyses were employed to assess their effectiveness in distinguishing dementia subtypes from healthy controls under eyes closed (EC) and eyes open (EO) conditions. RESULTS: Classic Fast-Fourier Transform (FFT) and autoregressive (AR) power analyses differentiated between all conditions for the 4-8 Hz theta range. Only individuals with dementia with Lewy Bodies (DLB) differed from healthy subjects for the wider 4-15 Hz frequency range, encompassing the actual dominant frequency of all individuals. FFT results for this range yielded wider significant discriminators vs AR, also detecting differences between AD and DLB. Analyses of the inclusive dominant / peak frequency range (4-15 Hz) indicated slowing and reduced variability, also discriminating between synucleinopathies vs controls and AD. Dissociation of periodic oscillations and aperiodic components of AR spectra using Fitting-Oscillations-&-One-Over-F (FOOOF) modelling delivered a reliable and subtype-specific slowing of brain oscillatory peaks during EC and EO for all groups. Distinct and robust differences were particularly strong for aperiodic parameters, suggesting their potential diagnostic power in detecting specific changes resulting from age and cognitive status. CONCLUSION: Our findings indicate that qEEG methods can reliably detect dementia subtypes. Spectral analyses comprising an integrated, multi-parameter EEG approach discriminating between periodic and aperiodic components under EC and EO conditions may enhance diagnostic accuracy in the future.

Abnormal Cerebrovascular Activity, Perfusion, and Glymphatic Clearance in Lewy Body Diseases.

Cerebrovascular activity is not only crucial to optimal cerebral perfusion, but also plays an important role in the glymphatic clearance of interstitial waste, including α-synuclein. This highlights a need to evaluate how cerebrovascular activity is altered in Lewy body diseases. This review begins by discussing how vascular risk factors and cardiovascular autonomic dysfunction may serve as upstream or direct influences on cerebrovascular activity. We then discuss how patients with Lewy body disease exhibit reduced and delayed cerebrovascular activity, hypoperfusion, and reductions in measures used to capture cerebrospinal fluid flow, suggestive of a reduced capacity for glymphatic clearance. Given the lack of an existing framework, we propose a model by which these processes may foster α-synuclein aggregation and neuroinflammation. Importantly, this review highlights several avenues for future research that may lead to treatments early in the disease course, prior to neurodegeneration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Multidimensional assessment of social cognition using non-immersive virtual reality in dementia with Lewy bodies and Alzheimer's disease: an exploratory study.

INTRODUCTION: Few studies have focused on social cognition in dementia with Lewy bodies (DLB), even though some brain structures being well known as underlying social cognitive processes are directly impacted in this disease. Furthermore, social cognition processes have been mostly studied independently using evaluations with poor ecological validity. We aimed at studying the ability of a new naturalistic and multidimensional social cognition task to reveal impairments in DLB patients. We chose to compare the profile of these patients with that of Alzheimer's disease (AD) patients, for which social cognition is better preserved. METHOD: Fifteen patients (DLB: n = 7; AD: n = 8) and 28 healthy controls underwent the REALSoCog task. They encountered several social situations (e.g. control versus transgressions) in a non-immersive virtual city environment allowing the assessment of moral cognition, cognitive and affective theory of mind (ToM), emotional empathy and behavioral intentions. RESULTS: The main results showed (i) a lower ability to detect transgressions in DLB patients, particularly conventional ones, whereas moral cognition seemed better preserved in AD patients; (ii) a cognitive ToM impairment in both DLB and AD patients, while affective ToM is impaired only in DLB patients; (iii) a decreased emotional empathy specifically observed in DLB patients; (iv) more inappropriate behavioral intentions, mainly in DLB patients, but also in some AD patients. CONCLUSIONS: This study suggests the feasibility and potential interest of the REALSoCog task in revealing social cognition deficits, particularly for DLB patients by showing different social patterns as compared to AD patients. These results offer interesting clinical perspectives to develop more naturalistic tasks in such populations and for clinical differential diagnosis. Limitations and future perspectives are discussed.

Cognitive trajectories preluding the onset of different dementia entities: a descriptive longitudinal study using the NACC database.

OBJECTIVE: To describe the 10-year preclinical cognitive trajectories of older, non-demented individuals towards the onset of the four most prevalent types of dementia, i.e., Alzheimer's disease(AD), Lewy body(LBD), vascular(VD) and frontotemporal dementia(FTD). METHODS: Our analysis focused on data from older (≥ 60years) NACC (National Alzheimer's Coordinating Center) participants. Four distinct presymptomatic dementia groups (AD-LBD-VD-FTD) and a comparison group of cognitively unimpaired(CU) participants were formed. Comprehensive cognitive assessments involving verbal episodic memory, semantic verbal fluency, confrontation naming, mental processing speed - attention and executive function - cognitive flexibility were conducted at baseline and on an approximately yearly basis. Descriptive analyses (adjusted general linear models) were performed to determine and compare the yearly cognitive scores of each group throughout the follow-up. Exploratory analyses were conducted to estimate the rates of cognitive decline. RESULTS: There were 3343 participants who developed AD, 247 LBD, 108 FTD, 155 VD and 3398 composed the CU group. Participants with AD performed worse on episodic memory than those with VD and LBD for about 3 to 4 years prior to dementia onset (the FTD group documented an intermediate course). Presymptomatic verbal fluency and confrontation naming trajectories differentiated quite well between the FTD group and the remaining dementia entities. Participants with incident LBD and VD performed worse than those with AD on executive functions and mental processing speed-attention since about 5 years prior to the onset of dementia, and worse than those with FTD more proximally to the diagnosis of the disorder. CONCLUSIONS: Heterogeneous cognitive trajectories characterize the presymptomatic courses of the most prevalent dementia entities.

Progressive QTc prolongation and reduced heart rate variability in dementia with Lewy bodies compared to Alzheimer's disease.

INTRODUCTION: Autonomic dysfunction (AuD) is a significant clinical challenge in patients with Dementia with Lewy Bodies (DLB). Manifestations of AuD such as orthostatic hypotension (OH) is associated with falls and decreased quality of life. Cardiac autonomic denervation is an early phenomenon in DLB and a potential contributor to OH. This retrospective study was undertaken to explore whether routine ECG tracings could be used to identify signs of autonomic dysfunction in DLB. METHODS: 18 patients with DLB and 18 age-matched patients with Alzheimer's disease (AD) were included. ECGs and clinical data were analyzed retrospectively for heart rate variability (HRV) and QTc interval prolongation. RESULTS: During an average of 10 years observation time (first to last ECG recording), the QTc interval increased in the DLB group, but not in the AD group. HRV was significantly lower at end of follow-up in the DLB group than in the AD group. DLB patients with OH had greater QTc prolongation. CONCLUSION: Longitudinal ECG analysis indicates that signs of AuD in DLB are reflected on routine ECG tracings. If confirmed in larger cohorts, this could influence risk stratification and help direct preventive measures.

Electroencephalographic spectro-spatial covariance patterns related to phenoconversion in isolated rapid eye movement sleep behavior disorder and their longitudinal trajectories in α-synucleinopathies.

STUDY OBJECTIVES: This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD) patients and explore their longitudinal trajectories within α-synucleinopathies. METHODS: We assessed 47 participants, including 35 patients with iRBD and 12 healthy controls (HC), through baseline eye-closed resting EEGs. Patients with iRBD underwent follow-up EEG assessments and 18 patients with iRBD converted (12 to Parkinson's disease (PD), 6 to dementia with Lewy bodies [DLB]) during follow-up. We derived EEG spectro-spatial covariance patterns for PD-RBD and DLB-RBD from converters and HC. Correlations with motor and cognitive function, baseline distinctions among iRBD converters and nonconverters, and longitudinal trajectories were examined. RESULTS: At baseline, converters exhibited higher PD-RBD and DLB-RBD beta2 pattern scores compared to nonconverters (each area under curve [AUC] = 0.7751). The delta and alpha spatial patterns effectively distinguished both PD and DLB converters from HC, with the alpha pattern showing high discriminative power (AUC = 0.9097 for PD-RBD, 0.9306 for DLB-RBD). Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III scores correlated positively with PD-RBD and DLB-RBD delta patterns (Spearman's rho = 0.688, p = 0.00014; rho = 0.539, p = 0.0055, respectively), with age and sex as cofactors. Distinct trajectories emerged during follow-up among PD converters, DLB converters, and iRBD nonconverters. CONCLUSIONS: Unique EEG spectro-spatial patterns specific to PD-RBD and DLB-RBD offer potential as predictive markers for phenoconversion to α-synucleinopathies in iRBD.

Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study.

We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6-22 and HR: 3.6, 95% CI: 1.1-12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2-6), trouble swallowing (HR 2.5, 95% CI: 1.4-4.5) and changes in speech (HR:2.4, 95% CI:1.1-4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1-5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2-38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6-46), preserved olfaction (HR: 8.7, 95% CI: 1.7-45), anhidrosis (HR: 1.8, 95% CI: 1-3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1-2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.

EEG-based machine learning models for the prediction of phenoconversion time and subtype in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies and eventually phenoconverts to overt neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Associations of baseline resting-state electroencephalography (EEG) with phenoconversion have been reported. In this study, we aimed to develop machine learning models to predict phenoconversion time and subtype using baseline EEG features in patients with iRBD. METHODS: At baseline, resting-state EEG and neurological assessments were performed on patients with iRBD. Calculated EEG features included spectral power, weighted phase lag index, and Shannon entropy. Three models were used for survival prediction, and four models were used for α-synucleinopathy subtype prediction. The models were externally validated using data from a different institution. RESULTS: A total of 236 iRBD patients were followed up for up to 8 years (mean 3.5 years), and 31 patients converted to α-synucleinopathies (16 PD, 9 DLB, 6 MSA). The best model for survival prediction was the random survival forest model with an integrated Brier score of 0.114 and a concordance index of 0.775. The K-nearest neighbor model was the best model for subtype prediction with an area under the receiver operating characteristic curve of 0.901. Slowing of the EEG was an important feature for both models. CONCLUSIONS: Machine learning models using baseline EEG features can be used to predict phenoconversion time and its subtype in patients with iRBD. Further research including large sample data from many countries is needed to make a more robust model.

Quantitative EEG in the Differential Diagnosis of Dementia Subtypes.

OBJECTIVE: Most neurodegenerative dementias present with substantial overlap in clinical features. Therefore, differential diagnosis is often a challenging task necessitating costly and sometimes invasive diagnostic procedures. A promising, non-invasive and cost-effective method is the widely available electroencephalography (EEG). METHODS: Twenty-three subjects with Alzheimer's disease (AD), 28 subjects with dementia with Lewy bodies (DLB), 15 subjects with frontotemporal dementias (FTDs), and 22 healthy controls (HC) were enrolled. Nineteen channel computerized EEG recordings were acquired. Mean relative powers were calculated using the standard frequency bands. Theta/alpha ratio (TAR), theta/beta ratio (TBR), a spectral index of (alpha + beta)/(theta + delta) and an alpha reactivity index (alpha in eyes-open condition/alpha in eyes-closed condition) were also calculated. Receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy. RESULTS: For the comparison of EEG measures across groups, we performed a multivariate ANOVA followed by univariate ANOVAs controlling for the effects of age, with post hoc tests. Theta power and TBR were increased in DLB compared to other groups. Alpha power was decreased in DLB compared to HC and FTD; and in AD compared to FTD. Beta power was decreased in DLB compared to AD and HC. Furthermore, regional analyses demonstrated a unique pattern of theta power increase in DLB; affecting frontal, central, parietal, occipital, and temporal regions. In AD, theta power increased compared to HC in parietal, occipital, and right temporal regions. TAR was increased in DLB compared to other groups; and in AD compared to HC. Finally, alpha reactivity index was higher in DLB compared to HC and FTD. In AD, EEG slowing was associated with cognitive impairment, while in DLB, this was associated with higher DLB characteristics. In the ROC analyses to distinguish DLB from FTD and AD, measures of EEG slowing yielded high area under curve values, with good specificities. Also, decreased alpha reactivity could distinguish DLB from FTD with good specificity. EEG slowing in DLB showed a diffuse pattern compared to AD, where a posterior and temporal slowing predominated. CONCLUSION: We showed that EEG slowing was satisfactory in distinguishing DLB patients from AD and FTD patients. Notably, this slowing was a characteristic finding in DLB patients, even at early stages, while it paralleled disease progression in AD. Furthermore, EEG slowing in DLB showed a diffuse pattern compared to AD, where a posterior and temporal slowing predominated. These findings align with the previous evidence of the diencephalic dysfunction in DLB.

Young-onset dementia with Lewy Bodies presenting with apathy and alexithymia.

A diagnosis of young-onset dementia can pose a significant challenge for the clinician. We present a young patient with a very unusual presentation of Dementia with Lewy Bodies. The lack of motor symptoms and his marked apathy delayed his diagnosis. His symptoms were thought to be due to depression based on normal structural imaging and the psychiatric nature of his presentation. An extensive work-up was performed. Evidence of a structural neurodegenerative process was provided by the HMPAO-SPECT. Cardiac MIBG confirmed the diagnosis.

Neuroimaging alterations in dementia with Lewy bodies and neuroimaging differences between dementia with Lewy bodies and Alzheimer's disease: An activation likelihood estimation meta-analysis.

AIMS: The aim of this study was to identify brain regions with local, structural, and functional abnormalities in dementia with Lewy bodies (DLB) and uncover the differences between DLB and Alzheimer's disease (AD). The neural networks involved in the identified abnormal brain regions were further described. METHODS: PubMed, Web of Science, OVID, Science Direct, and Cochrane Library databases were used to identify neuroimaging studies that included DLB versus healthy controls (HCs) or DLB versus AD. The coordinate-based meta-analysis and functional meta-analytic connectivity modeling were performed using the activation likelihood estimation algorithm. RESULTS: Eleven structural studies and fourteen functional studies were included in this quantitative meta-analysis. DLB patients showed a dysfunction in the bilateral inferior parietal lobule and right lingual gyrus compared with HC patients. DLB patients showed a relative preservation of the medial temporal lobe and a tendency of lower metabolism in the right lingual gyrus compared with AD. The frontal-parietal, salience, and visual networks were all abnormally co-activated in DLB, but the default mode network remained normally co-activated compared with AD. CONCLUSIONS: The convergence of local brain regions and co-activation neural networks might be potential specific imaging markers in the diagnosis of DLB. This might provide a pathway for the neural regulation in DLB patients, and it might contribute to the development of specific interventions for DLB and AD.

Impact of neurodegenerative diseases on human adult hippocampal neurogenesis.

Disrupted hippocampal performance underlies psychiatric comorbidities and cognitive impairments in patients with neurodegenerative disorders. To understand the contribution of adult hippocampal neurogenesis (AHN) to amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, dementia with Lewy bodies, and frontotemporal dementia, we studied postmortem human samples. We found that adult-born dentate granule cells showed abnormal morphological development and changes in the expression of differentiation markers. The ratio of quiescent to proliferating hippocampal neural stem cells shifted, and the homeostasis of the neurogenic niche was altered. Aging and neurodegenerative diseases reduced the phagocytic capacity of microglia, triggered astrogliosis, and altered the microvasculature of the dentate gyrus. Thus, enhanced vulnerability of AHN to neurodegeneration might underlie hippocampal dysfunction during physiological and pathological aging in humans.

Progression of Clinical Features in Lewy Body Dementia Can Be Detected Over 6 Months.

OBJECTIVE: This study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), including global cognition, parkinsonism, recurrent visual hallucinations, cognitive fluctuations, and sleep disturbance. METHODS: One hundred sixteen patients with Lewy body dementia (DLB = 72, PDD = 44) underwent assessment at baseline and 3 and 6 months as part of a prospective multicenter randomized controlled trial. Linear mixed models were constructed for core outcome measures using the Mini-Mental State Examination (MMSE), motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III), Dementia Cognitive Fluctuations Scale (DCFS), and Neuropsychiatric Inventory (NPI). RESULTS: Within the time frame of our study (6 months), we were able to identify a significant cognitive decline of 1.3 points on the MMSE (p = 0.002) and significant worsening of motor parkinsonism with an increase in UPDRS-III score of 3.2 points (p = 0.018). Fluctuation severity also increased using the DCFS with a 6-month change in score of 1.3 points (p = 0.001). Uniquely, a signal for increased severity of sleep symptoms of 1.2 points (NPI-sleep) was also detectable (p = 0.04). Significant changes in neuropsychiatric symptoms were not detected. There was no difference in rates of change of scores between DLB and PDD. DISCUSSION: Clinically significant rates of change in core clinical features can be detected and quantified in Lewy body dementia over a relatively short period (6 months) using common clinical instruments and thus may be useful as clinical endpoints for therapeutic trials of disease-modifying and symptomatic agents.

Association of Lewy Bodies With Age-Related Clinical Characteristics in Black and White Decedents.

OBJECTIVE: The associations of Lewy bodies (LBs) with olfactory dysfunction, parkinsonism, and higher odds of dementia were assessed in Black and White community-dwelling elders and racial differences in these associations were tested. METHODS: Black decedents (n = 81) were matched 2-to-1 by age, sex, years of education, and follow-up time in the study with White decedents (n = 154) from 4 longitudinal studies of dementia and aging. Participants underwent uniform clinical examination and cognitive, motor, and olfactory testing. LBs were detected in 7 brain regions by α-synuclein immunohistochemistry and racial differences in their association with olfaction, parkinsonism, and odds of dementia were determined using regression analyses. RESULTS: The mean scores of the odor test, global parkinsonism signs, and global cognition were lower in Black than White decedents; the frequency of dementia was similar in both groups. The frequency of LBs was similar in Black and White decedents (∼25%), as was the frequency of LBs in individual brain regions, while the mean LB counts/mm2 were similar in all regions except the cingulate cortex, which showed higher mean LB counts in Black decedents. In regression analyses, LBs were associated with impaired olfaction (-2.23, 95% confidence interval [CI] -3.45 to -1.01) and higher odds of dementia (odds ratio 3.0, 95% CI 1.10-8.17) in both racial groups; an association with parkinsonism was stronger in Black than White decedents. CONCLUSIONS: The frequency, distribution, and clinical manifestations of LBs are similar in Black and White elders.