Prevalence of cerebral microbleeds in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia: A systematic review and meta-analysis.

Cerebral microbleeds (CMB) are often associated with vascular risk factors and/or cerebral amyloid angiopathy and are frequently identified in people with dementia. The present study therefore aimed to estimate the pooled prevalence and associations of CMB in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), using meta-analytic methods. Sixty-five MRI studies were included after a systematic search on major electronic databases. We found that the prevalence of CMB was comparable across the three dementia subtypes (31-36%) and was highly influenced by the MRI techniques used. CMB in AD were associated with a history of hypertension and amyloid-ß burden. In contrast, CMB in DLB, despite being predominantly lobar, were associated with hypertension, but not amyloid-ß burden. These findings suggest that the underlying pathophysiology of CMB in DLB might differ from that of AD. There was substantially larger number of AD studies identified and more studies evaluating CMB in Lewy body dementias are warranted.

Tau in dementia with Lewy bodies.

OBJECTIVE: Neurofibrillary tangles are present in a proportion of people with dementia with Lewy bodies and may be associated with worse cognition. Recent advances in biomarkers for Alzheimer's disease include second-generation tau positron emission tomography as well as the detection of phosphorylated tau at threonine 181 (p-tau181) in plasma. This study aimed to investigate tau in people with dementia with Lewy bodies using a second-generation tau positron emission tomography tracer as well as plasma p-tau181. METHODS: Twenty-seven participants (mean age 74.7 ± 5.5) with clinically diagnosed probable dementia with Lewy bodies underwent comprehensive clinical assessment and positron emission tomography imaging (18F-MK6240 and 18F-NAV4694). Plasma p-tau181 levels were measured using Simoa technology. RESULTS: Five dementia with Lewy bodies participants (18.5%) had an abnormal tau positron emission tomography (increased tau uptake in the temporal meta-region-of-interest). Higher plasma p-tau181 concentrations correlated with higher tau deposition in the temporal region (ρ = 0.46, 95% confidence interval = [0.10, 0.72]) and classified abnormal tau positron emission tomography in dementia with Lewy bodies with an area under the curve of 0.95 (95% confidence interval = [0.86, 0.99]). Plasma p-tau181 also correlated positively with cortical amyloid-beta binding (ρ = 0.68, 95% confidence interval = [0.40, 0.84]) and classified abnormal amyloid-beta positron emission tomography in dementia with Lewy bodies with an area under the curve of 0.91 (95% confidence interval = [0.79, 0.99]). There was no association found between tau deposition and any of the clinical variables. CONCLUSIONS: Tau is a common co-pathology in dementia with Lewy bodies. Plasma p-tau181 correlated with abnormal tau and amyloid-beta positron emission tomography and may potentially be used as a marker to identify co-morbid Alzheimer's disease-related pathology in dementia with Lewy bodies. The clinical implications of tau in dementia with Lewy bodies need to be further evaluated in larger longitudinal studies.

Pathophysiology of dementia.

BACKGROUND: Dementia is a debilitating neurological condition that affects millions of patients and families worldwide and remains a significant public health concern. Understanding the underlying neurobiology and pathophysiology of dementia is an important step towards finding effective treatment options. OBJECTIVE: This article provides an overview of the pathophysiological processes of the most common types of dementia in older adults and highlights some of the developments in the research of biomarkers. DISCUSSION: The most common forms of late-onset dementia are Alzheimer's disease, dementia with Lewy bodies, vascular dementia and frontotemporal dementia. The pathophysiology of dementia is broadly characterised by the aggregation of misfolded proteins (such as amyloid-ß plaques and neurofibrillary tangles in Alzheimer's disease) and cerebrovascular disease. Mixed neuropathologies are frequently detected in the brains of older people with dementia and have important clinical implications.

Association between amyloid-beta deposition and cortical thickness in dementia with Lewy bodies.

OBJECTIVE: Amyloid-beta often co-exists in dementia with Lewy bodies, but its clinical relevance in dementia with Lewy bodies remains unclear. This study aimed to investigate the clinical and imaging correlates of amyloid-beta deposition in dementia with Lewy bodies, particularly its relationship with cortical thickness in Alzheimer's disease-prone regions and hippocampal volume. METHODS: Twenty-four participants with probable dementia with Lewy bodies underwent high-resolution magnetic resonance imaging and amyloid-beta positron emission tomography imaging using the radiotracer 18F-NAV4694. Amyloid-beta deposition was quantified and reported using the Centiloid method. RESULTS: Amyloid-beta positivity, defined as Centiloid > 50, was present in 45.8% of dementia with Lewy bodies participants. There were no statistically significant differences in clinical characteristics between Aß+ and Aß- dementia with Lewy bodies. Compared with the Aß- group, Aß+ dementia with Lewy bodies exhibited greater global cortical thinning as well as in the Alzheimer's disease-prone region of interest, adjusted for age, sex and years of education. A mean cortical thickness of 5.12 mm across a combined meta-region of interest has a sensitivity of 88.9% and specificity of 90.0% in discriminating Aß+ from Aß- dementia with Lewy bodies. Hippocampal volume was not different between groups. CONCLUSION: Early structural changes in cortical thickness, but not hippocampal volume, were observed in dementia with Lewy bodies with significant amyloid-beta burden. This may represent an early Alzheimer's disease-related neurodegenerative process.

Cerebral microbleeds in dementia with Lewy bodies.

INTRODUCTION: Cerebral microbleeds (CMB) are associated with cognitive impairment and hypertensive or cerebral amyloid angiopathy. The pathophysiology and clinical significance of CMB in dementia with Lewy bodies (DLB) are not well understood. Our study aimed to investigate the prevalence of CMB in DLB and to estimate the magnitudes of their clinical associations. METHODS: Twenty participants with DLB (mean age 74 ± 5 years) were included in this cross-sectional study. All participants underwent 3 T magnetic resonance imaging. CMB number and location were assessed on susceptibility-weighted imaging or quantitative susceptibility mapping. Amyloid-beta (Aß) positron emission tomography (PET) scans were also performed. Between-group comparisons were estimated using risk ratios (RR) for categorical variables, and mean differences or median regression coefficients for continuous variables. RESULTS: CMB were present in 30% of the DLB participants, with a lobar predominance observed. DLB with CMB were more likely to be on antithrombotic therapy (100%), compared to those without CMB (43%; RR 2.33 [95% CI 1.27, 4.27]). Those with CMB were also more likely to report a history of hypertension (100%) compared to those without (70%; RR 1.75 [95% CI 1.11, 2.75]). DLB core clinical features, cognition and functional status did not differ between the two groups. There was no association found between the presence of CMB and cortical Aß deposition on PET imaging. CONCLUSION: CMB are not uncommon in DLB and may be associated with hypertensive small vessel disease. Further studies into the pathophysiology and clinical implications of CMB in DLB are needed.

Prevalence and clinical associations of tau in Lewy body dementias: A systematic review and meta-analysis.

INTRODUCTION: Alzheimer's disease neuropathologies (amyloid-ß and tau) frequently co-exist to varying degrees in Lewy body dementias (LBD), which include dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). OBJECTIVES: To investigate the prevalence of tau in DLB and PDD, and its associations with clinical outcomes. METHODS: We searched the major electronic databases using the search term: ("dementia with Lewy bodies" OR "diffuse Lewy body disease" OR "Lewy body variant of Alzheimer's disease") AND ("tau protein" OR "tauopathy" OR "neurofibrillary tangle"), for relevant studies which evaluated tau in LBD. Forty-nine articles met the inclusion criteria for data extraction. Where appropriate, a random-effect meta-analysis was performed to obtain pooled estimates for prevalence and risk ratios (RR) or standardized mean differences (SMD) for clinical features, diagnostic accuracy and cognition. RESULTS: Braak neurofibrillary tangle stage ≥ III was observed in 66% (n = 1511, 95%CI 60%-73%) of DLB and 52% (n = 433, 95%CI 27%-76%) of PDD at autopsy. Abnormal CSF phosphorylated-tau levels were present in 28% (n = 925, 95%CI 25%-31%) of DLB and 15% (n = 172, 95%CI 5%-24%) of PDD cases. Higher tau burden in DLB was associated with reduced likelihood of manifesting visual hallucinations (RR 0.56; 95%CI 0.40-0.77) and motor parkinsonism (RR 0.62; 95%CI 0.40-0.98), lower diagnostic accuracy of DLB during life (RR 0.49; 95%CI 0.38-0.64) and worse cognition prior to death (SMD 0.63; 95%CI 0.46-0.81). CONCLUSIONS: Tau is common in LBD and may reduce clinical diagnostic accuracy in people with DLB. Prospective longitudinal studies are needed to understand the roles of co-morbid neuropathologies in Lewy body dementias.

Does successful treatment of overactive bladder improve co-morbidities in patients with nocturia?

OBJECTIVE: To investigate whether treatment of overactive bladder (OAB), one comorbidity of nocturia, could reduce waking to void and improve other co-existing symptoms. METHODS: A prospective cohort study was conducted at Royal Melbourne Hospital. Participants received 12 weeks of standard treatment, including lifestyle interventions and pharmacotherapy. Outcome measures were nocturia episodes, severity of urinary urgency/incontinence, sleep quality, daytime somnolence, anxiety and depression scores, quality of life and change in blood pressure. RESULTS: Twenty participants completed the study. Nocturia frequency improved by one void per night. Overactive Bladder Symptom Score, sleep quality, first uninterrupted sleep time and systolic blood pressures improved. There were no significant changes in daytime somnolence, mood or quality of life. CONCLUSIONS: In this pilot study, nocturia and other co-morbid dysfunctions appeared to improve when the severity of OAB was reduced. Treatment of OAB co-morbid with nocturia reduces urinary symptoms and may improve sleep parameters and positively impact return to health.

Dementia with Lewy bodies: Challenges in the diagnosis and management.

OBJECTIVE: Dementia with Lewy bodies is the second most common form of neurodegenerative dementia in older age yet is often under-recognised and misdiagnosed. This review aims to provide an overview of the clinical features of dementia with Lewy bodies, discussing the frequent challenges clinicians experience in diagnosing dementia with Lewy bodies, and outlines a practical approach to the clinical management, particularly in the Australian setting. METHODS: This paper is a narrative review and a semi-structured database (PubMed and MEDLINE) search strategy was implemented. Articles were screened and clinically relevant studies were selected for inclusion. RESULTS: Dementia with Lewy bodies is clinically characterised by complex visual hallucinations, spontaneous motor parkinsonism, prominent cognitive fluctuations and rapid eye movement sleep behaviour disorder. Neuropsychiatric features and autonomic dysfunction are also common. The new diagnostic criteria and specific diagnostic biomarkers help to improve detection rates and diagnostic accuracy, as well as guide appropriate management. Clinical management of dementia with Lewy bodies is challenging and requires an individualised multidisciplinary approach with specialist input. CONCLUSION: Dementia with Lewy bodies is a common form of dementia. It often presents as a diagnostic challenge to clinicians, particularly at early stages of disease, and in patients with mixed neuropathological changes, which occur in over 50% of people with dementia with Lewy bodies. Prompt diagnosis and comprehensive treatment strategies are important in improving patients' care.