Dementia Syndrome Research Articles

Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability.

Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.

A call for globally responsive screening materials to account for heterogeneity in dementia syndromes.

Effective screening for communicative ability in dementia is vital to drive theoretical understanding and optimize care responsiveness globally. Communication is central to the human experience; however, routine clinical screening for progressive communication change remains limited due to a variety of resource constraints. Other challenges include the subtlety of early communication-led symptoms, heterogeneous underlying pathologies, and a lack of culturally diverse research and tools. To address the scarcity of dedicated assessment resources, future initiatives must maximize responsiveness to and representation of our global population to appropriately respond to the rising, and vastly diverse, dementia crisis.

Anthropometric and Demographic Features Affect the Interpretation of Cerebrospinal Fluid Biomarkers in Patients with Different Dementia Syndromes and Cognitively Healthy Adults.

Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ42,Aβ40,Aβ38), tau, and phospho-tau Thr181. Overall, 81 participants were included with DLB (n = 27;11 APOE-ε4 +) or AD (n = 27;12 APOE-ε4 +), and controls (n = 27;4 APOE-ε4 +); two thirds were women. Cerebrospinal fluid evidence of amyloidosis and tauopathy was more prevalent among women with AD, while Aβ42/Aβ38 could also discriminate men with DLB from men with AD. Restructured traditional regression formulas had higher diagnostic accuracy for women with AD. Aging, higher body mass index, and APOE-ε4 alleles were associated with amyloidosis in DLB, while only in AD were higher body mass index associated with lower tau pathology load, and more alcohol use associated with higher phospho-tau Thr181/Aβ42. These findings confirm the effects of anthropometric and demographic features on cerebrospinal fluid biomarkers, and also differences in aberrant amyloidosis and tauopathy between DLB and AD.

Premorbid autistic traits in phenocopy syndrome of behavioral variant frontotemporal dementia: an autopsy revealing primary age-related tauopathy

Premorbid autistic traits in phenocopy syndrome of behavioral variant frontotemporal dementia: an autopsy revealing primary age-related tauopathy

Use of Trazodone in the Management of Psychomotor Agitation in Dementia Syndromes

Use of Trazodone in the Management of Psychomotor Agitation in Dementia Syndromes

Capgras Syndrome in Dementia: A Systematic Review of Case Studies.

In an ageing population, dementia has become an imminent healthcare emergency. Capgras syndrome, the most common delusion of misidentification (DMS), is frequently found alongside dementia. Previous research showed that Capgras syndrome has significant negative effects on people living with dementia and their carers due to its complex presentation and impact on their lives. This qualitative systematic review explores the evidence base of the effective management and treatment of Capgras syndrome in dementia. As per our knowledge, this is the first systematic review exploring the symptomatology of Capgras syndrome across different types of dementia. Additionally, it aims to identify the treatments used and their efficacy. Four databases (EMBASE, MEDLINE, PsycINFO, and CINHAL) were screened in March, 2023. Twenty-six studies met the inclusion criteria and were included in the review. Thematic analysis was performed to explore and synthesise the qualitative findings of the studies. Three conceptual themes were identified: diagnostic tools, Capgras syndrome symptomatology, and Capgras syndrome treatment. Results showed that Capgras syndrome in dementia is not diagnosed and treated in a standardised manner. Following the pharmacological intervention, 28% of cases showed resolution of symptoms, and another 28% experienced improvement. However, 7% of cases reported worsening symptoms, and 10.7% experienced no change. While some patients had positive outcomes with specific medications, others either did not respond or experienced a deterioration of their condition. The results highlight that there is no single treatment approach for Capgras syndrome in people living with dementia. This underscores the need for person-centred care, where treatment is tailored to individual needs. The review also reveals a heavy reliance on antipsychotic medications and a noticeable lack of psychosocial interventions. Given the limited benefits and significant risks associated with antipsychotics, future research should prioritise developing and testing psychosocial approaches. Additionally, establishing standardised diagnostic criteria and consistent outcome measures for Capgras syndrome in dementia is crucial for evaluating treatment effectiveness and improving care.

Neuropsychiatric presentations of common dementia syndromes: A concise review for primary care team members.

Dementia is a syndrome characterized by cognitive changes which interfere with daily functioning. Neuropsychiatric symptoms (NPS) are also pervasive and may even occur prior to any noticeable cognitive decline. Still, NPS are less associated with the early stages of the disease course, despite mounting research evidence that NPS present early and often in several dementia syndromes, even in the absence of cognitive decline (i.e., mild behavioral impairment [MBI]). Primary care teams are at the forefront of dementia care, yet they frequently report insufficient training in dementia diagnosis and management. This poses a serious problem considering that timely diagnosis of dementia is critical for optimal outcomes and maximum efficacy of intervention. We provide a concise narrative review of four dementia syndromes (Alzheimer's disease, vascular dementia, dementia with Lewy bodies, and behavioral variant frontotemporal dementia) and their associated neuropsychiatric presentations, as well as at-a-glance clinical guides, to help primary care team members recognize possible prodromal neurodegenerative disease and to prompt further workup. We also review next steps in the management of dementia and symptoms of MBI for primary care team members. As evidenced by the NPS profiles of these dementia syndromes, subacute new onset of psychiatric symptoms in an older adult should prompt consideration of an emerging dementia process and possible further workup of such, even in the absence of cognitive decline.

Soundscape augmentation as a nonpharmacological intervention to reduce the behavioural effect of dementia: a randomized controlled trial

Soundscape is an important environmental factor that influences people's behaviour and well-being. People with dementia can benefit from a personalized soundscape to improve the behavioural and psychological syndrome of dementia. This paper is based on a single-blind, repeated-measure pilot randomized clinical trial of soundscape augmentation on the treatment effect of people with severe dementia. Participants were randomized to a personalized soundscape intervention delivered in their room in the morning and evening or treatment-as-usual, with two baseline weeks and four weekly post-randomization assessments of the primary and secondary behavioural outcomes. A linear mixed effects model showed that the soundscape intervention was possible and acceptable. There were improvements in the Neuropsychiatric Inventory (resistance to care) and a significant reduction in aggression in the soundscape group. This study is the first pilot randomized controlled trial of a soundscape intervention for older adults with dementia to improve the behavioural and psychological syndrome of dementia. In this pilot study, soundscape augmentation was a feasible and effective non-pharmacological approach to reducing resistance and improving participants' behaviour. Further studies with larger samples are recommended to confirm our findings. Longitudinal studies are necessary to investigate the long-term effect of an augmented sonic environment on people with dementia.

Longitudinal changes in functional capacity in frontotemporal dementia and Alzheimer's disease

AbstractINTRODUCTIONThis study investigated the changes in functional capacity with disease progression in a well‐characterised cohort of patients diagnosed with frontotemporal dementia (FTD) and Alzheimer's disease (AD) presentations.METHODSWe recruited 126 behavioural variant FTD (bvFTD), 40 progressive nonfluent aphasia (PNFA), 64 semantic dementia (SD), 45 logopenic progressive aphasia (LPA), and 115 AD patients. Functional capacity was measured annually over ∼7 years using the Disability Assessment for Dementia.RESULTSLinear mixed effects models revealed the bvFTD group demonstrated disproportionate functional impairment at baseline and over the study period. Functional capacity among the other syndromes showed a more uniform pattern of decline, with less severe functional impairment at baseline and ∼7%–10% mean annual decline. Baseline correlations indicated different mechanisms supporting basic and complex functional proficiency among the groups.DISCUSSIONOur findings demonstrate distinct functional profiles across dementia syndromes with disease progression. Identifying progression milestones across syndromes will improve clinical management.Highlights bvFTD shows severe functional impairment at baseline and over time. PNFA, SD, LPA, AD: less severe baseline functional impairment; more uniform decline. General cognition is related to IADLs, but not BADLs, in all groups. Behavioural disturbances relate to IADLs and BADLs in bvFTD and SD. Behavioural‐ADL relations are more mixed in PNFA, LPA, and AD.

Practical Assessment of Neuropsychiatric Symptoms: Updated Reliability, Validity, and Cutoffs for the Neuropsychiatric Inventory Questionnaire

ObjectivesTo improve assessment of neuropsychiatric symptoms (NPS) by expanding the measurement properties of the Neuropsychiatric Inventory Questionnaire (NPI-Q). DesignMulticenter, longitudinal observational study. SettingSeveral Alzheimer's Disease Research Centers (ADRCs). ParticipantsIndividuals who presented to an ADRC with a collateral and completed the NPI-Q. MeasurementsThe NPI-Q total severity score, four NPI-Q subscales, dementia stage, expert NPS rating, consensus rating of dementia syndrome, global cognitive screening, collateral rating of daily functioning, and self-rating of depression. ResultsThere was strong evidence of criterion validity with both dementia stage and expert NPS rating for the NPI-Q total severity index, which informed cutoffs and interpretive ranges. Furthermore, subscales had adequate classification of dementia syndromes and appropriate convergent relationships with cognition, daily functioning, and mood. There was good-to-excellent evidence of reliability for the NPI-Q total severity index over several years, and subscales had adequate-to-good reliability. ConclusionsThis is the first study to provide empirically established cutoffs, interpretive ranges, and evidence of reliability over a period longer than a month on the NPI-Q and its subscales. This will improve assessment of NPS in clinical and research contexts. Article SummaryNeuropsychiatric symptoms of neurodegeneration are increasingly understood as early disease markers with tremendous functional impact later in disease, but are often missed or misdiagnosed. The most common measure of these symptoms, the Neuropsychiatric Inventory Questionnaire (NPI-Q), does not have clinically actionable guidance, which this article provided. We established cutscores for several conditions and test-retest reliability over longer periods for the total score and subscales using a multicenter database.

Increased nocturnal urinary cortisol levels in the elderly patients with depression, coexisting major geriatric syndromes and combined pathogenetic mechanisms

BackgroundThe mechanisms at the basis of depression are still matter of debate, but several studies in the literature suggest common pathways with dementia (genetic predispositions, metabolic and inflammatory mechanisms, neuropathological changes) and other geriatric syndromes.AimsTo evaluate the role of cortisol (as marker of the HPA, hypothalamus–pituitary–adrenal axis hyperactivity) in elderly subjects with depressive symptoms (by the means of the AGICO, AGIng and COrtisol, study), in relationship to the presence of the major geriatric syndromes.MethodsThe AGICO study enrolled patients from ten Geriatric Units in Italy. Every subject received a comprehensive geriatric assessment or CGA (including the Mini Mental State Examination or MMSE, Geriatric Depression Scale or GDS and Cornell Scale for Depression in Dementia or CSDD), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal), a CGA-derived frailty index (FI) and a modified measure of allostatic load (AL).ResultsThe MMSE scores were significantly and inversely related to the values of GDS (p < 0.001) and CSDD (p < 0.05), respectively. The patients with depressive symptoms (GDS/CSDD > 8) showed significantly increased disability, MetS, inflammation, FI and AL and significantly reduced MMSE and renal function.The diurnal and nocturnal urinary cortisol levels in the patients with depressive symptoms (GDS/CSDD > 8) were higher with respects to controls (p < 0.05 for nocturnal difference).DiscussionThe AGICO study showed that the stress response is activated in the patients with depression.ConclusionThe depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome.

AS CONTRIBUIÇÕES DA NEUROPSICOLOGIA NO TRATAMENTO NÃO MEDICAMENTOSO DAS DEMÊNCIAS EM IDOSOS

Dementia syndromes are a group of disorders characterized by a progressive and global decline in cognitive functions, such as memory, language, attention, reasoning, and judgment. These changes significantly interfere with a person’s ability to perform daily activities and interact socially. Although the use of drugs is the basis for the treatment of dementia syndromes, non-pharmacological and therapeutic treatment is an important ally in these cases. Neuropsychology presents itself as an essential resource for the implementation of non- pharmacological treatment, where it can monitor its progress and carry out cognitive rehabilitation. Neuropsychological rehabilitation presents strategies that help reduce cognitive deficits and is applied in the treatment of cognitive alterations of reasoning, attention, memory, communication, and others. This intervention aims to support individuals so that they can improve their functions in important areas of their lives. This article aims to analyze how Neuropsychology performs the treatment of dementias, presenting its interventions and therapeutic approaches. In addition, we aim to investigate how these interventions can bring benefits to the quality and independence in their activities of daily living.

A - 124 A Case of Lewy Body Dementia and Charles Bonnet Syndrome in a Patient with Bilateral Enucleation

Abstract Objective The patient presented with a history of blindness due to bilateral enucleation (age 10 and 23) and visual hallucinations for approximately 2 years. Approximately 30% of visually impaired individuals are affected by Charles Bonnet syndrome, characterized by complex visual hallucinations in visually challenged patients, possibly stemming from the brain’s attempt to fill the visual void. Additionally, she was diagnosed with Lewy Body dementia (LBD) 2 years prior by her neurologist, and she reported challenges with completing instrumental activities of daily living (IADLs). Method The patient was a left-handed 83-year-old woman, with a history of total blindness and bilateral enucleation, who presented with progressive memory loss 3–4 years prior, along with balance/gait disturbances for 1–1.5 years. The patient and her family sought neuropsychological testing to clarify her cognitive functioning in light of her physical and neurologic symptoms. Results Premorbid functioning was estimated in the low average range, with 11 years of education. Due to her total vision loss, neuropsychological evaluation was limited. Her cognitive profile was marked by impairments in immediate memory, delayed memory, recognition, executive functioning, and language. Conclusions In light of the patient’s marked cognitive deficits in memory, attention, and executive functioning, along with visual hallucinations (although also attributed to possible Charles Bonnet syndrome), balance/gait disturbances, fluctuating awareness, autonomic dysfunction (i.e., bladder/bowel control), and sleep changes (i.e., acting out dreams), her presentation is consistent with LBD, in the moderate stage of severity. Given the symptomatology, it raises the possibility the patient may be experiencing Charles Bonnet syndrome along with LBD.

Inappropriate trusting behaviour in dementia.

Inappropriate trusting behaviour may have significant social, financial and other consequences for people living with dementia. However, its clinical associations and predictors have not been clarified. Here we addressed this issue in canonical syndromes of frontotemporal dementia (FTD) and Alzheimer's disease (AD). In 34 patients with AD and 73 with FTD (27 behavioural variant (bv)FTD, 22 semantic variant primary progressive aphasia (svPPA), 24 nonfluent/agrammatic variant (nfv)PPA) we recorded inappropriate trusting and other abnormal socio-emotional behaviours using a semi-structured caregiver survey. Patients were comprehensively characterised using a general cognitive assessment and the Revised Self-Monitoring Scale (RSMS; an informant index of socioemotional awareness). Inappropriate trusting was more frequent in svPPA (55%) and bvFTD (44%) than nfvPPA (17%) or AD (24%). After adjusting for age, sex, education and Mini-Mental State Examination (MMSE) score, inappropriate trusting was significantly more likely in svPPA (odds ratio 3.61; 95% confidence interval 1.41-8.75) and bvFTD (3.01, 1.23-6.65) than AD. Significant predictors of inappropriate trusting comprised apathy in svPPA, disinhibition and altered pain responsiveness in bvFTD, and lower MMSE and RSMS (self-presentation) scores in AD. Dementia syndromes vary in prevalence and predictors of abnormal trusting behaviour, with implications for clinical counselling and safeguarding.

Nurses' Beliefs About Pain Assessment in Dementia: A Qualitative Study Informed by the Theory of Planned Behaviour.

To explore registered nurses' beliefs regarding pain assessment in people living with dementia. A descriptive exploratory qualitative study informed by the Theory of Planned Behaviour. Online semi-structured in-depth interviews were conducted from January to April 2023 with a purposive sample of 15 registered nurses caring for people with dementia. Following transcription, data were analysed using direct content analysis. Registered nurses believe pain assessment improves the well-being of people with dementia and informs and evaluates practice. However, there is a possibility of misdiagnosing pain as agitation or behavioural problems, leading to inaccurate pain management. Interpersonal factors, such as registered nurses' knowledge and experience, beliefs and motivation to improve care provision, were the primary facilitators of pain assessment. Physical and behavioural dimensions of the pain of the dementia syndrome were the most reported barriers to pain assessment. Registered nurses reported that multidisciplinary team members expect them to do pain assessments. Most did not experience disapproval when performing pain assessments. Registered nurses hold beliefs about pain assessment benefits, consequences, enablers, barriers, approvals and disapprovals regarding dementia. The findings could inform interventions to enhance pain assessment practices. Policymakers should provide education opportunities for registered nurses to improve their knowledge, skills and beliefs about pain assessment in dementia. Future research should develop and implement multidisciplinary, multifaceted pain assessment protocols to enhance the accuracy of pain assessment practices. Pain is underassessed in dementia, and this could stem from registered nurses' beliefs about pain assessment in dementia. The findings could inform interventions to enhance pain assessment beliefs and practices. This study adhered to the COREQ criteria. Registered nurses caring for people living with dementia participated as interview respondents.

Lyme Neuroborreliosis in the Context of Dementia Syndromes.

Lyme disease (LD) can affect the skin, joints, heart, and nervous system as a multisystemic condition. The cause of the illness is the spirochete of the genus Borrelia. These pathogens can affect the skin, joints, heart, and nervous system. Lyme neuroborreliosis (LNB) is the term for the disease, which occurs when the nervous system gets involved. Regarding geographical distribution, LNB is more prevalent in Europe than in North America. The most significant change in pathogenesis is inflammation of the central nervous system (CNS) and peripheral nervous system (PNS). Furthermore, clinically, it can represent a variety of neurological manifestations, such as meningitis, encephalitis, radiculopathies, and cranial neuritis. However, dementia-like syndrome is an infrequent manifestation of Lyme disease. Our review article aims to summarize the similarities and differences between dementia-like syndrome in LNB and that in primary neurodegenerative diseases, as well as to look for a correlation between the pathogenesis of the disease and the possibility of developing dementia-like syndrome. The world literature lacks sufficiently convincing data on the relationship between spirochete infection and primary dementia syndromes. However, cases of secondary dementia syndrome due to nervous system involvement as well as post-treatment have been described. A thorough examination, medical history, laboratory and imaging studies, cerebrospinal fluid (CSF) examination, MRI, and fludeoxyglucose-18-positron emission tomography (FGD-PET) are required to differentiate between these syndromes.

A Critical Review of Noninvasive Brain Stimulation Technologies in Alzheimer's Dementia and Primary Progressive Aphasia.

Multiple pharmacologic agents now have been approved in the United States and other countries as treatment to slow disease and clinical progression for Alzheimer's disease. Given these treatments have not been proven to lessen the cognitive deficits already manifested in the Alzheimer's Clinical Syndrome (ACS), and none are aimed for another debilitating dementia syndrome identified as primary progressive aphasia (PPA), there is an urgent need for new, safe, tolerable, and efficacious treatments to mitigate the cognitive deficits experienced in ACS and PPA. Noninvasive brain stimulation has shown promise for enhancing cognitive functioning, and there has been interest in its potential therapeutic value in ACS and PPA. This review critically examines the evidence of five technologies in ACS and PPA: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), repetitive transcranial magnetic stimulation (rTMS), and noninvasive vagus nerve stimulation (nVNS). Many randomized controlled trials of tDCS and rTMS report positive treatment effects on cognition in ACS and PPA that persist out to at least 8 weeks, whereas there are few trials for tACS and none for tRNS and nVNS. However, most positive trials did not identify clinically meaningful changes, underscoring that clinical efficacy has yet to be established in ACS and PPA. Much is still to be learned about noninvasive brain stimulation in ACS and PPA, and shifting the focus to prioritize clinical significance in addition to statistical significance in trials could yield greater success in understanding its potential cognitive effects and optimal parameters.

Quantum mechanical, spectroscopic, docking studies (Dementia & breast cancer) and in-vitro assays of phytochemical compound Dehydrozingerone by DFT

Density functional theory (DFT) based quantum computing techniques were used to study the phytochemical compound Dehydrozingerone (DHZ), which originated from the ginger plant Zingiber officinale. Structural analyses, of the title compound such as FTIR, FTR, and Ultraviolet-Visible (UV-Vis) are performed both theoretically and experimentally. DHZ was optimized for the most stable molecular structure. Vibrational frequencies were scaled using a scaling factor, and prominent peaks were identified. Potential energy distribution (%PED) assignments were also examined to determine the percentage of vibrational transitions. Four different solvents were quantitatively analyzed using TD-DFT from UV-Vis spectra. HOMO-LUMO calculations were performed to forecast Dehydrozingerone's stability and non-toxicity. The Natural Bond Orbital (NBO) method was used to study inter- and intra-molecular interactions. DOS spectra were convoluted to analyse the overlapping interactions of the various bonds present in DHZ. Population analysis, such as Mulliken and Natural, was conducted to determine the charge distribution within the compound. Topological analyses such as ELF, LOL and reactive site of DHZ were identified using MEP. Non-linear optical (NLO) behaviour was further studied and compared to urea, a prototype substrate. Drug likeness and Ramachandran plot were determined. Using the Autodock tools for molecular docking studies, the pharmaceutical importance of DHZ was analysed for targeted proteins 4MS4 (anticonvulsant), 7AIX (dementia syndrome), 7E9B (anti-brain cancer) and 7C00 (anti-breast cancer). The biological activity of breast cancer was analysed both theoretically (protein) and experimentally (MCF7). The standard drug was theoretically studied for the four proteins, and binding energies are comparable, implying that DHZ could be a suitable drug for the control and treatment of anti-convulsant, dementia, brain tumours and breast cancer. To better understand the toxicity and bioavailability of the title compound, cytotoxicity assays were also performed.

Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease.

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with a higher risk of dementia and, consequently, be not rarely misdiagnosed. In this review, we summarize the current understanding of LBD-AD by discussing the synergistic effects of AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment for use in LBD-AD and their possible diagnostic and prognostic values. AD pathology can be predicted in vivo by means of CSF, MRI and PET markers, whereas the most promising technique to date for identifying Lewy pathology in different biological tissues is the α-synuclein seed amplification assay. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity as in pure AD. Implementing the use of blood-based AD biomarkers might allow faster screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account when considering differential diagnoses of dementia syndromes, to allow prognostic evaluation on an individual level, and to guide symptomatic and disease-modifying therapies.

Unexpected Low Rate of Amyloid-β Pathology in Multiple Sclerosis Patients.

The life expectancy of people with multiple sclerosis (MS) has increased, yet we have noted that development of a typical Alzheimer disease dementia syndrome is uncommon. We hypothesized that Alzheimer disease pathology is uncommon in MS patients. In 100 MS patients, the rate of amyloid-β plasma biomarker positivity was approximately half the rate in 300 non-MS controls matched on age, sex, apolipoprotein E proteotype, and cognitive status. Interestingly, most MS patients who did have amyloid-β pathology had features atypical for MS at diagnosis. These results support that MS is associated with reduced Alzheimer disease risk, and suggest new avenues of research. ANN NEUROL 2024;96:453-459.