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This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimers disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)-parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

BackgroundThe reliability of the Progressive Supranuclear Palsy Rating Scale (PSPRS) using teleneurology has not been assessed.ObjectivesTo test whether removing items inadequately assessed by video would impact measurement of PSP severity and progression.MethodsWe performed secondary analyses of two data sets: the phase 2/3 trial of Davunetide in PSP and a large single-center cohort. We examined two modifications of the PSPRS: (1) removing neck rigidity, limb rigidity, and postural stability (25 items; mPSPRS-25) and (2) also removing three ocular motor items and limb dystonia (21 items; mPSPRS-21). Proportional agreement relative to the possible total scores was measured using the intraclass correlation coefficient, compared to the original PSPRS baseline values and change over 6 and 12 months. We examined the ability of both scales to predict survival in the single-center cohort using proportional hazards models.ResultsThe mPSPRS-25 showed excellent agreement (0.99; P

ObjectiveTo evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB).MethodsSupine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales.ResultsA total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72).ConclusionsOH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.

Background and purposeDespite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization.MethodsThe Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members.ResultsSurvey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe.ConclusionsThis survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes. They center on rigidity, bradykinesia, postural instability, gait freezing, supranuclear ocular motor impairment, dysarthria, dysphagia, incontinence, sleep disorders, frontal cognitive dysfunction, and a variety of behavioral changes. CBS presents with prominent and usually asymmetric dystonia, apraxia, myoclonus, pyramidal signs, and cortical sensory loss. The symptoms and deficits of PSP and CBS are amenable to a variety of treatment strategies but most physicians, including many neurologists, are reluctant to care for patients with these conditions because of unfamiliarity with their multiplicity of interacting symptoms and deficits. CurePSP, the organization devoted to support, research, and education for PSP and CBS, created its CurePSP Centers of Care network in North America in 2017 to improve patient access to clinical expertise and develop collaborations. The directors of the 25 centers have created this consensus document outlining best practices in the management of PSP and CBS. They formed a writing committee for each of 12 sub-topics. A 4-member Steering Committee collated and edited the contributions. The result was returned to the entire cohort of authors for further comments, which were considered for incorporation by the Steering Committee. The authors hope that this publication will serve as a convenient guide for all clinicians caring for patients with PSP and CBS and that it will improve care for patients with these devastating but manageable disorders.

Background: Expedient diagnosis of incipient dementia is often hindered by time constraints in primary care visits, shortage of dementia specialists, and extended waitlists for comprehensive neuropsychological evaluations. Methods: We developed the Rapid Access Memory Program (RAMP) to improve access of neuropsychological services for older adults presenting to our institutional primary care clinics with concerns of cognitive decline. RAMP provides abbreviated neurocognitive assessment, same-day patient feedback, expedited reporting to referring providers, and is financially self-supported. Here, we describe development of RAMP and clinical outcomes from the first 3 years. Results: Of 160 patients seen, dementia was diagnosed in 30% and Mild Cognitive Impairment in 50%; Alzheimer's disease was the most common suspected etiology. New psychiatric diagnosis was made in about one-third (n = 54). Most frequent recommendations involved medication adjustments (initiating cholinesterase inhibitors, deprescribing anticholinergics), safety (driving, decision-making), and specialist referrals. Additionally, 27 (17%) subsequently enrolled in local research. Conclusions: Results support feasibility and utility of RAMP for connecting older adults in primary care with neuropsychological services. [ABSTRACT FROM AUTHOR]

Poststroke movement disorders (PSMDs) are a common cause of secondary movement disorders. Although prior studies have highlighted the clinical spectrum and phenomenology of PSMDs, there are many knowledge gaps worth addressing. Some of the most important include lack of clinical definitions, variable stroke symptom latencies, and lack of biomarkers for vulnerability for or resilience against developing PSMDs. Collectively, the association between stroke localization and phenomenology is less than 30%, and the long-term clinical prognosis and treatment responses are highly variable. After summarizing the accumulated evidence regarding the phenomenology, pathophysiology, neuroimaging, and treatment of PSMDs, highlighting the many gaps and controversies including diagnostic challenges, we propose a roadmap for future research to fill these gaps and resolve the related controversies. More research is warranted concerning the phenomenology, classification, diagnostic criteria, and pathophysiology of PSMDs. Further, there is an urgent need for treatment guidelines for the management of PSMDs. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Complex visual hallucinations (VH) are a common complication of Parkinson's disease (PD). Recent studies have demonstrated relevance of face pareidolia to VH in PD and Lewy body dementia (LBD). Objective: This study examined utility of the 20‐item Noise Pareidolia Task (NPT‐20) in assessing visuoperceptual disturbances associated with VH in PD. Methods: Retrospective chart review included 46 consecutive PD patients who completed NPT‐20 during clinical neuropsychological evaluation. Results: About half the sample (43%) reported VH. PD with VH made significantly more false‐positive pareidolia errors on the NPT‐20 (p < 0.0001). A cut‐off of 2 errors yielded 40% sensitivity, 100% specificity to VH; cut‐off of 1 yielded 75% sensitivity, 81% specificity. NPT‐20 was not associated with any other clinical or demographic factor. Across groups, NPT‐20 evinced moderate correlations with visuospatial functioning and visual memory. Conclusions: Current findings support utility of the NPT‐20 for evaluating visuoperceptual disturbances associated with VH in PD. [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA‐binding protein 43 (TDP‐43), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co‐pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co‐pathologies in DLB and their cross‐sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease‐specific and disease‐nonspecific biomarkers and how co‐pathologies can impact these biomarkers. We propose a framework for integrating multi‐modal biomarker fingerprints and step‐wise selection and assessment of DLB individuals for clinical trials, monitoring target engagement, and interpreting outcomes in the setting of co‐pathologies. [ABSTRACT FROM AUTHOR]