Dementia Syndrome Research Articles

Characteristics of the Dementia Syndrome in Primary Health Care

Characteristics of the Dementia Syndrome in Primary Health Care

Charting the Next Road Map for CSF Biomarkers in Alzheimer's Disease and Related Dementias.

Clinical prediction of underlying pathologic substrates in people with Alzheimer's disease (AD) dementia or related dementia syndromes (ADRD) has limited accuracy. Etiologic biomarkers - including cerebrospinal fluid (CSF) levels of AD proteins and cerebral amyloid PET imaging - have greatly modernized disease-modifying clinical trials in AD, but their integration into medical practice has been slow. Beyond core CSF AD biomarkers (including beta-amyloid 1-42, total tau, and tau phosphorylated at threonine 181), novel biomarkers have been interrogated in single- and multi-centered studies with uneven rigor. Here, we review early expectations for ideal AD/ADRD biomarkers, assess these goals' future applicability, and propose study designs and performance thresholds for meeting these ideals with a focus on CSF biomarkers. We further propose three new characteristics: equity (oversampling of diverse populations in the design and testing of biomarkers), access (reasonable availability to 80% of people at risk for disease, along with pre- and post-biomarker processes), and reliability (thorough evaluation of pre-analytical and analytical factors influencing measurements and performance). Finally, we urge biomarker scientists to balance the desire and evidence for a biomarker to reflect its namesake function, indulge data- as well as theory-driven associations, re-visit the subset of rigorously measured CSF biomarkers in large datasets (such as Alzheimer's disease neuroimaging initiative), and resist the temptation to favor ease over fail-safe in the development phase. This shift from discovery to application, and from suspended disbelief to cogent ingenuity, should allow the AD/ADRD biomarker field to live up to its billing during the next phase of neurodegenerative disease research.

Mild behavioral impairment checklist : English-German translation and feasibility study assessing its use in clinical practice

The mild behavioral impairment (MBI) syndrome is defined by the emergence in later life of persistent neuropsychiatric symptoms. The MBI checklist (MBI-C) can be used for systematic detection and documentation of such symptoms. Development of aGerman version of the MBI‑C and assessment of its application in aclinical setting. The MBI‑C was translated from English into German in collaboration with the main author of the original version, and its practical application was then tested on astudy population (n = 21) in agerontopsychiatric inpatient clinic. Patient compliance, understanding of questions, time effort, evaluation procedure and possible discrepancy between patient and family member evaluations were assessed. The German translation of the original MBI‑C obtained certification as an official version and can be downloaded at https://mbitest.org . All 34questions were fully completed by the study population, the level of understanding of questions was good, with the mean time effort being 16 min. In some cases, significant differences between patients' and family members' responses were found. The presence of MBI may indicate the development of an otherwise presymptomatic neurodegenerative dementia syndrome. Hence, the MBI‑C could aid in the early detection of neurodegenerative dementia. By means of the translated version of the MBI‑C presented in this study, this hypothesis can now be tested in German-speaking countries.

Antipsychotic Use and Mortality in Persons with Alcohol-Related Dementia or Wernicke-Korsakoff Syndrome: A Nationwide Register Study in Finland.

Research on the use of psychotropic drugs in people with alcohol-related neurocognitive disorders is virtually nonexistent. We examined the prevalence of antipsychotic drug use and its effect on mortality among patients with Wernicke-Korsakoff syndrome (WKS) or alcohol-related dementia (ARD). In this nationwide register study, we collected data on the medication use and mortality of all persons aged ≥40 diagnosed with WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the prevalence of antipsychotic use within one year of diagnosis and the adjusted cumulative mortality of antipsychotic users versus non-users in relation to the age-, sex-, and calendar year-matched general population. Of the WKS and ARD patients, 35.9% and 38.5%, respectively, purchased one or more antipsychotic drugs in the year following diagnosis. The adjusted cumulative mortality of the antipsychotic users was significantly lower than that of non-users in both the WKS and ARD groups, where the adjusted hazard ratios (95% CI) were 0.85 (0.72-0.99) and 0.73 (0.65-0.81), respectively. WKS and ARD patients using antipsychotics were less likely to die of alcohol-related causes than antipsychotic non-users, but the difference was significant only in the ARD group. This population-based study shows that antipsychotic use is common in patients with WKS or ARD. In contrast to other dementia studies, our results indicate that the mortality of antipsychotic users is significantly lower than that of non-users. The lower mortality could be explained by decreased alcohol use and better healthcare coverage in antipsychotic users.

Familial Creutzfeld-Jakob disease, compatible with PRNP c.532G>A (p.Asp178sn) gene mutation

Background: Prion disease is a rare entity; a prevalence between 0.32-1.73 per million people is estimated. The familial form corresponds to 10% of the total cases, with a peak of presentation between 40-50 years. Over fourty known germline mutations have been described, the most frequent being c.598G>Ap.Glu200Lys (E200K). Case presentation: A 41-year-old man who began in November 2021 with progressive memory impairment. In April 2022 tremor was added in all four limbs, with balance disturbances. A neurological examination with data compatible with dementia, pancerebellar and parkinsonian syndromes. Magnetic resonance imaging showed symmetrical and bilateral hyperintensities of the basal ganglia. Due to the findings and family history, a sequencing search for the PrP gene was performed, resulting in a mutation of the PrPSc gene c.532G>A (p. Asp178sn), compatible with a familial variant of Creutzfeldt Jacob Disease. Conclusions: Prionopathy should be considered as a diagnosis to rule out in people with rapidly progressive dementia. Although there are both clinical and paraclinical diagnostic criteria, diagnosis through DNA sequencing is necessary to determine de novo or autosomal dominant hereditary mutations.

Multi-approach comparative study of EEG patterns associated with the most common forms of dementia

Electroencephalography’s (EEG) sensitivity in discriminating dementia syndromes remains unclear. This study aimed to investigate EEG markers in patients with major cognitive disorders. The studied population included 4 groups of patients: Alzheimer's disease with associated vascular lesions, Alzheimer’s disease without vascular lesions (AD-V), Lewy body disease and vascular dementia (VaD); and completed by a control group composed by cognitively unimpaired patients. EEGs were analysed quantitatively using spectral analysis, functional connectivity and micro-states. By comparison to the controls, expected slowing and alterations of functional connectivity were detected in patients with dementia. Among these patients, an overall increase in power in the alpha band was observed in the VaD group, mainly when compared to the 2 AD groups, while the Alzheimer’s disease without vascular lesions group exhibited increased power in the beta-2 band and higher functional connectivity in the same frequency band. Micro-state analyses revealed differences in temporal dynamics for the VaD group.A number of EEG modifications reported as markers of some syndromes were found, but others were not reproduced.

Predictors of Nursing Home Entry within 36 Months after Hospitalization via the Emergency Department among Persons Aged 75 Years or Older.

We aimed to identify risk factors for nursing home (NH) entry 36 months after hospitalization via the emergency department (ED) in a population of patients aged 75 years or older. This was a prospective multicentre cohort. Patients were recruited from the emergency departments (EDs) of nine hospitals. Subjects had been hospitalised in a medical ward in the same hospital as the ED to which they were initially admitted. Subjects who experienced NH entry prior to ED admission were excluded. NH entry has been defined as the incident admission either into an NH or other long-term care facility within the follow-up period. Variables from a comprehensive geriatric assessment of patients were entered into a Cox model with competing risks to predict NH entry during 3 years of follow-up. Among 1306 patients included in the SAFES cohort, 218 (16.7%) who were already in an NH were excluded. The remaining 1088 patients included in the analysis were aged 84 ± 6 years on average. During 3 years of follow-up, 340 (31.3%) entered an NH. The independent risk factors for NH entry were that they: living alone (Hazard ratio (HR) 2.00, had a 95% confidence interval (CI) 1.59-2.54, p < 0.0001), could not independently perform activities of daily living (HR 1.81, 95% CI 1.24-2.64, p = 0.002), and had balance disorders (HR 1.37, 95% CI 1.09-1.73, p = 0.007), dementia syndrome (HR 1.80, 95% CI 1.42-2.29, p < 0.0001) and a risk of pressure ulcers (HR 1.42, 95% CI 1.10-1.82, p = 0.006). The majority of the risk factors for NH entry within 3 years after emergency hospitalization are amenable to intervention strategies. It is therefore reasonable to imagine that targeting these features of frailty could delay or prevent NH entry and improve the quality of life of these individuals before and after NH entry.

Distinct and shared neuropsychiatric phenotypes in FTLD-tauopathies.

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy. Participants completed annual research visits at the Northwestern University Alzheimer's Disease Research Center. All participants had an initial Global Clinical Dementia Rating (CDR) Scale score ≤ 2, and neuropsychiatric symptoms were evaluated via the Neuropsychiatric Inventory-Questionnaire (NPI-Q). We assessed the frequency of neuropsychiatric symptoms across all participants at their initial and final visits and performed logistic regression to determine whether symptoms predicted a specific FTLD-tau pathologic diagnosis. Across the FTLD-tau cohort, irritability and apathy were most frequently endorsed at initial and final visits, respectively, whereas psychosis was highly uncommon at both timepoints. Irritability at initial visit predicted greater odds of a 4-repeat compared to a 3-repeat tauopathy (OR = 3.95, 95% CI = 1.10-15.83, p < 0.05). Initial sleep disturbance predicted greater odds of progressive supranuclear palsy (PSP) compared to other FTLD-tau subtypes (OR = 10.68, 95% CI = 2.05-72.40, p < 0.01). Appetite disturbance at final evaluation predicted lower odds of PSP (OR = 0.15, 95% CI = 0.02-0.74, p < 0.05). Our findings suggest that characterization of neuropsychiatric symptoms can aid in the prediction of underlying FTLD-tauopathies. Given considerable pathologic heterogeneity underlying dementias, neuropsychiatric symptoms may be useful for differential diagnosis and treatment planning.

Neuropsychological profile of CSF1R-related leukoencephalopathy.

The neuropsychological profile of CSF1R-related leukoencephalopathy (CRL) is undefined. This study defines the profile, contrasts it with that of other dementia syndromes, and highlights measures sensitive to cognitive impairment. We administered a standardized battery of neuropsychological tests to five consecutive CRL cases. The neuropsychological profile of CRL reflects impaired general cognitive function, processing speed, executive function, speeded visual problem solving, verbal fluency, and self-reported depression and anxiety. Confrontation naming and memory are preserved. Within cognitive domains, certain measures more frequently identified impairment than others. CRL impairs general cognitive function, processing speed, executive function. Language and visual problem solving may be impaired if processing speed is required. Confrontation naming and memory are uniquely preserved, contrasting CRL to other dementia syndromes. Cognitive screens excluding processing speed and executive function may not detect CRL cognitive manifestations. Findings sharply define cognitive impairment of CRL and inform cognitive test selection.

Cognitive and emotional theory of mind in dementia. Impact on real life behaviors

AbstractBackgroundTheory of mind (ToM) is a core cognitive process that allows regular socioemotional interaction in everyday life. ToM deficits may explain some essential behavior alterations in dementia, particularly in Alzheimer’s disease (AD) and frontotemporal dementia (FTD). This study aimed to (1) identify ToM differences across dementia syndromes and (2) determine if ToM scores predict neuropsychiatric function.MethodWe evaluated 304 participants (age 64.07±9.2) divided into six groups (healthy control, NC = 41; AD = 34; behavioral variant FTD = 96; semantic aphasia; svPPA = 38, nonfluent aphasia; nfvPPA = 47, and progressive supranuclear palsy; PSP = 48) using the UCSF Emotional and Cognitive ToM Test on the TabCAT platform and comprehensive neuropsychological and neuropsychiatric testing. Pa Patients were early in their disease (Clinical Dementia Rating: 0.80±0.53). We compared ToM between groups and used regression models controlling by age and sex to determine if ToM predicted neuropsychiatric symptoms.ResultCognitive ToM was impaired in AD, bvFTD, svPPA, and PSP (p&lt;0.0001), and all groups had impaired emotional ToM (p&lt;0.0001). Both cToM and eToM performance predicted a real‐life neuropsychiatric behavior syndrome, including anxiety, apathy, disinhibition, and aberrant motor subscales scores on the Neuropsychiatric Inventory questionnaire, even after controlling for the influence of bvFTD diagnosis.ConclusionCognitive and Emotional ToM are affected early in diverse dementia syndromes, and impaired ToM test performance can predict a real‐life neuropsychiatric behavior. Assessment of ToM and other aspects of social cognition can be beneficial for the early identification of behavioral alterations in dementia cases.

Clinical profile of primary progressive Aphasia in Peru: Case series from a Neurological care center

AbstractBackgroundPrimary Progressive Aphasia (PPA) is one of the clinical syndromes of frontotemporal dementia (1). The frequency of PPA syndromes is low (16%) in this Latin America, with just one published report in Peruvian population (2). We aim to describe clinical features of PPA patients followed up at a Neurological healthcare center in Peru.MethodRetrospective review of clinical records of patients diagnosed with probable PPA (based on 2011 diagnostic criteria) during the 2010‐2020 period. Local IRB approval was obtained for this study.ResultWe included 11 cases that fulfilled the selection criteria. Nine cases (75%) were categorized as nfvPPA, and 3 (25%) svPPA. There was slightly female predominance (58%). The average of education was 10.8±4.8 years. Six cases (54.5%) declared place of birth from northern Peru. We found 4.2±1.8 years of diagnostic delay for PPA. The mean age at onset for nfvPPA and svPPA groups was 63 ±12.4, and 52(52‐64) respectively. The first symptom identified in the nfvPPA group was effortful, halting speech 7 (77.8%), while svPPA was impaired confrontation naming 3 (100%). nfvPPA group showed agrammatism in language production and effortful speech in 8 patients (88.9%) and impaired in comprehension of syntactically complex sentences and spared single ‐word comprehension 3(33.3%). Parkinsonism was present in 6 patients (66.7%) and only one patient reported coexistence of amyotrophic lateral sclerosis. Depression was present in most of the 50% of cases. svPPA group also presented impaired in single word‐ comprehension, in object knowledge, and spared repetition 3(100%), 3 (100%) and 2(66.8%) respectively. Less than 50% of PPA cases were in speech therapy.ConclusionThe main clinical features of the PPA reported are mostly consistent with previous reports. In our medical records review, no cases of apraxia of speech were found. There is a significant delay of PPA diagnosis. Further studies with prospective design are required to obtain a better description. Implementing training strategies for clinicians will allow to improve the timely and accurate diagnosis of PPA in Peru.

Distinct regional and hemispheric tau distributions in Primary Progressive Aphasia with neuropathologic Progressive Supranuclear Palsy: A stereological study

AbstractBackgroundPrimary Progressive Aphasia (PPA) is a dementia syndrome characterized by isolated and progressive impairment of language and focal atrophy of left‐hemispheric cortical regions. PPA presents with various underlying FTLD‐tauopathies such as Pick’s disease (PiD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). This study investigated clinicopathologic concordance between the aphasic phenotype of PPA and regional distributions of PSP markers quantified in language‐related cortical areas and the dentate gyrus (DG) of the hippocampus—an area of interest due to intact memory exhibited in PPA. Another goal was to compare regional distributions of tau‐positive markers in PSP compared to CBD and PiD to identify differential susceptibility patterns across FTLD‐tauopathies.MethodParaffin‐embedded sections were stained immunohistochemically with AT‐8 to visualize neuronal tau inclusions and astrocytes containing phosphorylated tau in 8 right‐handed cases with PPA and autopsy‐confirmed PSP. Modified unbiased stereology was performed in bilateral middle frontal gyrus (MFG) and inferior parietal lobule (IPL), and left DG. A secondary analysis compared distributions of tau markers in cases with PiD (N = 6; tau‐positive inclusions) and CBD (N = 4; tau‐positive inclusions + astrocytic plaques). One‐way ANOVAs and students’ t‐tests were used to analyze distributions.ResultWithin the PSP group, there was significant left‐sided asymmetric predominance of tau‐positive neuronal inclusions and astrocytic tau in cortical areas; left MFG showed over double the total marker density vs right (3,490 vs 1,549 counts/mm3, respectively; p&lt;0.05). In PSP, there was significantly less tau‐positive inclusions and astrocytes in the DG relative to cortical regions, where the ratio of left‐sided dentate‐to‐cortical inclusions was ∼1:2. This was remarkably lower than dentate‐to‐cortical ratios of ∼2:1 in CBD and ∼3:1 in PiD (p&lt;0.01). Finally, PSP cases showed significantly greater astrocytic tau in cortical regions compared to CBD, by ∼100 fold in the left hemisphere (p&lt;0.01).ConclusionFindings from this stereological study of PPA with FTLD‐PSP show leftward cortical predominance of pathology concordant with the salience of the aphasic phenotype. Dentate predominance of pathology in PPA due to FTLD‐tau remains a mystery. The relative distribution of dentate‐to‐cortical tau pathology is different across FTLD‐tau species, offering insights into the selective vulnerability of distinct neuronal populations in neurodegenerative dementias.

The effect of single and repeated doses of rivastigmine on gastric myoelectric activity in experimental pigs.

Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs. Six experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes). In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 μV2; p = 0.004). Both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.

Pathologic TDP43 Associated Tri‐Glial Dysfunction in Amnestic and Non‐amnestic Clinical Dementia Syndromes: A Multiplexed Immunofluorescence Study

AbstractBackgroundAlzheimer’s disease (AD) is a substantial cause of death and disability. In addition to the plaques and tangles classically observed in AD, other co‐existing brain lesions also contribute to the development of cognitive impairment, such as pathologic trans‐active response DNA‐binding protein 43 (pTDP43). TDP43 is ubiquitously expressed in the brain and mechanistic studies suggest potential roles for TDP43 in maintaining normal physiologic conditions in glia (astrocytes, microglia, oligodendrocytes) (Bulgiani, 2022). Effective glial functioning and signaling are crucial to maintaining functional connectivity and pTDP43 is strongly associated with lower cognitive performance (Flanagan, 2018). However, pTDP43’s role in tri‐glial dysfunction remains unclear. We hypothesize that nuclear astrocytic TDP43 loss alters astrocyte‐to‐microglial signaling, and results in tri‐glial dysfunction. Here we examine glial pTDP43 subtypes in amnestic and non‐amnestic clinical dementia syndromes with matched AD pathology.MethodParaffin embedded autopsy samples (hippocampus and middle frontal cortex) were stained using multiplexed immunofluorescence (Pu.1: microglia, GLUL: astrocytes, total TDP43), and imaged. Indica Labs Halo software was used to perform quantitative analyses on whole slide images. Cases were matched for AD pathology (low and high) (Montine, 2012). Students’ t‐tests were performed to compare cell counts between groups. Kolmogorov–Smirnov test was performed to check approximate normality before applying t‐test and all measurements passed it. Clinical phenotypes (AD dementia vs. behavioral variant frontotemporal dementia (bvFTD)) and pTDP43 status were compared (n = 50). Spatial localization plots, NSInC colocalization indices, and Box plot comparisons were used to assess the impact of glial pTDP43 on the microenvironment.ResultHippocampal astrocyte counts are lowest in the AD dementia setting with the highest AD pathology burden, and presence of co‐existing pTDP43. Cases with high AD pathology had lower astrocyte counts when co‐existing pTDP43 was present when comparing both AD dementia with pTDP43 vs. AD dementia without pTDP43 (p = 0.03), and AD dementia with pTDP43 vs. bvFTD without pTDP43 (p = 0.05).ConclusionContradictory to studies showing increased GFAP in mutant TDP43 mice (Yan, 2014), the lowest astrocyte counts were found in individuals with AD dementia, highest burden of AD pathology, and presence of pTDP43. Results support the role of astroglial heterogeneity contributing to white matter dysfunction via selective vulnerability.

Comprehension of acoustically degraded speech in Alzheimer's disease and primary progressive aphasia.

Successful communication in daily life depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, comprehension of acoustically degraded speech in these diseases has been little studied. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer's disease and 30 patients representing the three canonical syndromes of primary progressive aphasia (non-fluent/agrammatic variant primary progressive aphasia; semantic variant primary progressive aphasia; logopenic variant primary progressive aphasia), compared to 25 healthy age-matched controls. As a paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility. We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients' brain images) were also assessed. Mean noise-vocoded speech intelligibility threshold was significantly higher in all patient groups than healthy controls, and significantly higher in Alzheimer's disease and logopenic variant primary progressive aphasia than semantic variant primary progressive aphasia (all P < 0.05). In a receiver operating characteristic analysis, vocoded intelligibility threshold discriminated Alzheimer's disease, non-fluent variant and logopenic variant primary progressive aphasia patients very well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in predefined regions of interest, impaired noise-vocoded speech comprehension across syndromes was significantly associated (P < 0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network that has previously been widely implicated in processing degraded speech signals. Our findings suggest that the comprehension of acoustically altered speech captures an auditory brain process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications.

The Future of Cognitive Screening in Neurodegenerative Diseases.

Cognitive screening instruments (CSI) have variable sensitivity and specificity to the cognitive changes associated with dementia syndromes, and the most recent systematic review found insufficient evidence to support the benefit of cognitive screening tools in older adults residing within the community. Consequently, there is a critical need to improve CSI methods, which have not yet incorporated advances in psychometrics, neuroscience, and technology. The primary goal of this article is to provide a framework for transitioning from legacy CSIs to advanced dementia screening measurement. In line with ongoing efforts in neuropsychology and the call for next-generation digital assessment for early detection of AD, we propose a psychometrically advanced (including application of item response theory methods), automated selective assessment model that provides a framework to help propel an assessment revolution. Further, we present a three-phase model for modernizing CSIs and discuss critical diversity and inclusion issues, current challenges in differentiating normal from pathological aging, and ethical considerations.

Sociodemographic, psychiatric and criminal characteristics of elderly offenders under evaluation for criminal responsibility in Turkey

ObjectiveThe aim of this study was to examine a sample (n = 150) of elderly offenders to analyse the psychiatric, medical, demographic, criminal and if available neuropsychological test characteristics and criminal responsibility. MethodData were gathered through a retrospective chart review of applicants aged 65 and over who were referred for determination of criminal responsibility from 2014 to 2019 at the Observation Department of Council of Forensic Medicine (Adli Tip Kurumu Baskanligi, Gözlem İhtisas Dairesi) who were evaluated under inpatient status by law. ResultsThere were 150 forensic cases aged 65 and over. The majority of the crimes were homicide (25.3%), homicide attempt (10%), and sexual offence (26%). The majority of sexual offence victims were children (34 of 39 cases). The percentages of decisions on criminal liability were as follows: 76% (n = 114) had full criminal liability, 21.3% of them (n = 32) had no criminal liability, 2.7% of them (n = 4) had reduced criminal liability. For the reduced/no criminal liability group, diagnoses were as follows: 37.1% dementia syndromes, 31.4% schizophrenia, 11.5% delusional disorder and 2.8% bipolar disorder manic episode. ConclusionWhen the findings in our study and current literature data are examined, it is seen that certain crime groups such as murder and attempted murder, and sexual crimes against children are high in elderly forensic psychiatric evaluations.

Aphasic Binary Reversals as a Novel Biomarker Across Dementia Syndromes (P6-6.010)

Aphasic Binary Reversals as a Novel Biomarker Across Dementia Syndromes (P6-6.010)

Predictors of Survival in Atypical Parkinsonian Syndromes in a Tunisian Cohort (P8-11.006)

<h3>Objective:</h3> Our aim was to investigate demographic, clinical and genetic survival factors in a Tunisian cohort with atypical parkinsonian syndromes (APS). <h3>Background:</h3> APS encompass a spectrum of neurodegenerative diseases including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS), all characterized by faster progression and earlier mortality compared to Parkinson’s disease. However, the predictors of survival are still controversial. <h3>Design/Methods:</h3> We conducted a retrospective study over a period of 19 years (2003–2021) in the Department of Neurology of Razi University Hospital, in Tunis, Tunisia, including patients diagnosed with APS. Survival was explored using Kaplan-Meier analysis. Demographic, clinical, neuropsychological features and frequency of Apolipoprotein Epsilon 4 (ApoEɛ4) allele were analyzed in the survival analysis. <h3>Results:</h3> We included 340 APS patients (151 DLB, 74 PSP, 70 MSA, 45 CBS). Median survival was 6 years from disease onset in DLB and MSA and 7 years in PSP and CBS. It was significantly shorter for men (p=0.005) and for patients with memory symptoms at onset (p=0.040) in DLB, later age of onset (&gt;65 years, p=0.021), earlier dysphagia and ApoEɛ4 allele carrying status in PSP patients. In MSA, median survival was shorter in parkinsonian subtype (MSA-P) compared to cerebellar subtype (MSA-C) in patients having urinary dysfunction. Although the presence of stridor was associated with shorter survival (6 vs 9 years), the difference was not statistically significant (p=0.090). In CBS, the presence of alien limb syndrome (p=0.031), dementia (p=0.026) and tremor-dominant parkinsonian syndrome (p=0.019) were associated with shorter survival. <h3>Conclusions:</h3> Our results showed shorter survival in synucleinopathies compared to tauopathies with different predictive demographic and clinical factors across APS. ApoEɛ4 seemed to have an effect only in PSP. Larger prospective studies are needed to better investigate the various survival determinants. <b>Disclosure:</b> Dr. Nasri has nothing to disclose. Ikram Sghaier has nothing to disclose. Mrabet Saloua has nothing to disclose. Mr. Abida has nothing to disclose. Alya GHARBI has nothing to disclose. Amira Souissi has nothing to disclose. Mouna BenDjebara has nothing to disclose. Amina Gargouri has nothing to disclose. Dr. Kacem has nothing to disclose. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Gouider has received research support from Clinical Investigation Center. The institution of Dr. Gouider has received research support from Menactrims.

Mortality and Survival of Patients with Central Nervous System Disorders: Prognostic Factors of at the University Hospital Point G, Bamako, Mali

The department of infectious and tropical diseases is the referral for all HIV positive patients in need of hospitalization. HIV has modified the epidemiology of central nervous system (CNS) disorders in Mali. Objective: Our objective was to study the prognostic factors of the mortality and survival of patients with CNS disorders in the department of infectious and tropical diseases at the University hospital Point G, Bamako, Mali. Methods: We collected data retrospectively from the medical records inpatients between 1st January 2013 and 31st December 2017 and we used R software version 2.12.2 to analyze data. Results: In five (5) years, we registered 1,315 hospital admissions with CNS disorders with a morbidity rate of 21.14% (278/1315) and 71.7% (125/278) were HIV positive. In bivariate analysis (Log-rank test), there was a statistically significant difference between survival and alcohol consumption (p=0.001) and smoking (p&lt;0.001); history of tuberculosis (p=0.006); presence of dementia syndrome (p&lt;0.001) and positive HIV serology (p=0.01). Multivariate analysis (Cox model) identified dementia [adjusted Hazard Risk, HR=13.02 (2.62 - 64.8)], previous tuberculosis [adjusted HR=13.33 (1.05 - 102.63)], alcohol use [adjusted HR=3.08 (1.67 - 5.69)] and smoking [adjusted HR= 2.9 (1.05 - 7.99)] as poor prognostic factors for survival. According to the Kaplan Meier method, the overall median survival of patients was 37 days [CI 95%; (35-55 days)]. Conclusion: Notion of TB, alcohol use and smoking were poor prognostic factors of the survival of HIV positive inpatients with CNS disorders.