Disparate Dementia Risk Factors Are Associated with Cognitive Impairment and Rates of Decline in African Americans.

OBJECTIVE: This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. METHODS: Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE ɛ4 status, and Area Deprivation Index. RESULTS: Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13-8.67) and nHW participants (OR = 2.79, 95% CI = 1.21-6.44) but uniquely associated with faster decline in AA participants (ß = 1.71, 95% CI = 0.69-2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (ß = 2.65, 95% CI = 0.38-4.91, p = 0.023). INTERPRETATION: Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518-529.

Protein analysis using capillary electrophoresis coupled to mass spectrometry through vibrating sharp-edge spray ionization.

Capillary electrophoresis (CE) interfaced to mass spectrometry (MS) with electrospray ionization typically incorporates acidic additives or organic solvents to assist in ionization. Vibrating sharp-edge spray ionization (VSSI) is a voltage-free method to interface CE and MS that does not require these additives, making it appealing for protein analyses. CE-VSSI nanoflow sheath separations are performed with low ionic strength aqueous solutions in the sheath to reduce suppression. Serine is also included in the sheath to reduce analyte adduction. Proteins are detected in the 2.5-10 µM range, corresponding to an injected mass range of 0.1-1.2 ng. The anionic proteins ß-lactoglobulin and transferrin are resolved using an unmodified fused silica capillary because they do not exhibit nonspecific surface adsorption. Conversely, separations of cationic proteins cytochrome c, ribonuclease A, and α-chymotrypsinogen A in an unmodified capillary require acidic background electrolytes to overcome adsorption. Alternatively, a semipermanent coating comprised self-assembled lipids overcomes surface adsorption at a neutral pH. Separations with zwitterionic and hybrid cationic coatings are complete within 15 or 6 min, respectively. The dimeric form of triosephosphate isomerase was observed at a 60 µM, corresponding to a mass of 19 ng, by dropping the temperature of the MS inlet.

Formation of Products of Incomplete Destruction (PID) from the Thermal Oxidative Decomposition of Perfluorooctanoic Acid (PFOA): Measurement, Modeling, and Reaction Pathways.

The thermal decomposition of perfluorooctanoic acid (PFOA) under oxidative conditions was investigated using air (O2) and N2O as oxidants over temperatures ranging from 400 to 1000 °C in an α-alumina reactor. In the presence of air, PFOA was found to decompose into perfluorohept-1-ene (C7F14) and perfluoroheptanoyl fluoride (C7F14O) in addition to HF, CO, and CO2. At temperatures above 800 °C, both C7F14 and C7F14O were no longer detected. A comprehensive analysis of the reaction mechanisms through quantum chemical analysis and kinetic modeling in combination with experimental observations was utilized to identify key reaction pathways. Quantum chemical analysis led to the conclusion that oxygen atoms are crucial in decomposing perfluoroalk-1-enes, especially the stable perfluorohept-1-ene (C7F14). Under oxidative conditions, it was found that significant quantities of C2F6 and CF4 were formed. Further quantum chemical analysis suggests that the O atoms facilitate the formation of volatile fluorinated compounds (VFCs) such as tetrafluoromethane (CF4) and hexafluoroethane (C2F6), particularly at higher temperatures. By elucidating these key reactions, an improved understanding of the potential formation products of incomplete combustion (PICs) or products of incomplete destruction (PIDs) is made.

Microscale Quantification of the Inhibition of Neuraminidase Using Capillary Nanogel Electrophoresis.

Neuraminidase inhibitors modulate infections that involve sialic acids, making quantitative analyses of this inhibitory effect important for selecting and designing potential therapeutics. An automated nanogel capillary electrophoresis system is developed that integrates a 5 nL enzyme inhibition reaction in line with a 5 min separation-based assay of the enzymatic product to quantify inhibition as the half maximal inhibitory concentration (IC50) and inhibitor constant (Ki). A neuraminidase enzyme from Clostridium perfringens is non-covalently immobilized in a thermally tunable nanogel positioned in the thermally controlled region of the capillary by increasing the capillary temperature to 37 °C. Aqueous inhibitor solutions are loaded into the capillary during the nanogel patterning step to surround the enzyme zone. The capillary electrophoresis separation provides a means to distinguish the de-sialylated product, enabling the use of sialyllactose which contains the trisaccharide motif observed on serine/threonine-linked (O-linked) glycans. A universal nanogel patterning scheme is developed that does not require pre-mixing of enzymes with inhibitors when an automated capillary electrophoresis instrument is used, thus reducing the consumption of enzymes and enabling adaption of the method to different inhibitors. The universal approach is successfully applied to two classical neuraminidase inhibitors with different electrophoretic mobilities. The IC50 and Ki values obtained for N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (DANA) are 13 ± 3 and 5.0 ± 0.9 µM, respectively, and 28 ± 3 and 11 ± 1 µM, respectively, for Siastatin B. These values agree with literature reports and reflect the weaker inhibition anticipated for Siastatin B in comparison to DANA.

Nanoflow Sheath Voltage-Free Interfacing of Capillary Electrophoresis and Mass Spectrometry for the Detection of Small Molecules.

Coupling capillary electrophoresis (CE) to mass spectrometry (MS) is a powerful strategy to leverage a high separation efficiency with structural identification. Traditional CE-MS interfacing relies upon voltage to drive this process. Additionally, sheathless interfacing requires that the electrophoresis generates a sufficient volumetric flow to sustain the ionization process. Vibrating sharp-edge spray ionization (VSSI) is a new method to interface capillary electrophoresis to mass analyzers. In contrast to traditional interfacing, VSSI is voltage-free, making it straightforward for CE and MS. New nanoflow sheath CE-VSSI-MS is introduced in this work to reduce the reliance on the separation flow rate to facilitate the transfer of analyte to the MS. The nanoflow sheath VSSI spray ionization functions from 400 to 900 nL/min. Using the new nanoflow sheath reported here, volumetric flow rate through the separation capillary is less critical, allowing the use of a small (i.e., 20 to 25 µm) inner diameter separation capillary and enabling the use of higher separation voltages and faster analysis. Moreover, the use of a nanoflow sheath enables greater flexibility in the separation conditions. The nanoflow sheath is operated using aqueous solutions in the background electrolyte and in the sheath, demonstrating the separation can be performed under normal and reversed polarity in the presence or absence of electroosmotic flow. This includes the use of a wider pH range as well. The versatility of nanoflow sheath CE-VSSI-MS is demonstrated by separating cationic, anionic, and zwitterionic molecules under a variety of separation conditions. The detection sensitivity observed with nanoflow sheath CE-VSSI-MS is comparable to that obtained with sheathless CE-VSSI-MS as well as CE-MS separations with electrospray ionization interfacing. A bare fused silica capillary is used to separate cationic ß-blockers with a near-neutral background electrolyte at concentrations ranging from 1.0 nM to 1.0 µM. Under acidic conditions, 13 amino acids are separated with normal polarity at a concentration ranging from 0.25 to 5 µM. Finally, separations of anionic compounds are demonstrated using reversed polarity under conditions of suppressed electroosmotic flow through the use of a semipermanent surface coating. With a near-neutral separation electrolyte, anionic nonsteroidal anti-inflammatory drugs are detected over a concentration range of 0.1 to 5.0 µM.

A Low-Cost and Simple Demonstration of Freezing Point Depression and Colligative Properties with Common Salts and Ice Cream.

A laboratory activity was developed to teach freezing point depression and colligative properties to introductory-level chemistry students. The laboratory uses food-grade reagents and is delivered in two units that can be taught in a single 2 hour session or two separate sessions. The total cost of the consumables is 1 USD. In the first part of this two-part activity, students perform measurements on the properties of five salt solutions to better know and understand freezing point depression. In the second part of the activity, students apply their knowledge and understanding of freezing point depression to make ice cream. The ice-cream-making experiment is delivered as a group activity to encourage reflection. Centering this experiment on ice cream allows students to connect properties described in chemistry to everyday life. The solutions used in the experiment are reusable and nonhazardous. The experiment can be implemented in a classroom, in a teaching laboratory, or at home.

Ethnoracial differences in Alzheimer's disease from the FLorida Autopsied Multi-Ethnic (FLAME) cohort.

INTRODUCTION: Our primary goal was to examine demographic and clinicopathologic differences across an ethnoracially diverse autopsy-confirmed cohort of Alzheimer's disease cases. METHODS: A retrospective study was conducted in the Florida Autopsied Multi-Ethnic cohort on 1625 Alzheimer's disease cases, including decedents who self-reported as Hispanic/Latino (n = 67), black/African American (n = 19), and white/European American (n = 1539). RESULTS: Hispanic decedents had a higher frequency of family history of cognitive impairment (58%), an earlier age at onset (median age of 70 years), longer disease duration (median of 12 years), and lower MMSE proximal to death (median of 4 points) compared with the other ethnoracial groups. Black decedents had a lower Braak tangle stage (stage V) and higher frequency of coexisting hippocampal sclerosis (21%); however, only hippocampal sclerosis differences survived adjustment for sex, age at onset, and disease duration. Neither Thal amyloid phase nor coexisting Lewy body disease differed across ethnoracial groups. DISCUSSION: Despite a smaller sample size, Hispanics demonstrated longer disease duration with Alzheimer's disease, but not greater lifespan. Neuropathologic differences across ethnoracial groups supported differences in tau pathology distribution and coexisting hippocampal sclerosis, which may impact biomarker studies.

The impact of stereotactic laser ablation at a typical epilepsy center.

PURPOSE: Stereotactic laser ablation (SLA) is a novel form of epilepsy surgery for patients with drug-resistant focal epilepsy. We evaluated one hundred consecutive surgeries performed for patients with epilepsy to address the impact of SLA on our therapeutic approach, as well as patient outcomes. METHODS: A retrospective, single center analysis of the last one hundred neurosurgeries for epilepsy was performed from 2013 to 2015. Demographics, surgical procedures, and postoperative measures were assessed up to 5years to compare the effect of SLA on outcome. Confidence intervals (CI) and comparative tests of proportions compared outcomes for SLA and resective surgery. Procedural categorical comparison used Chi-square and Kaplan-Meier curves. Student t-test was utilized for single variables such as age at procedure and seizure onset. RESULTS: One hundred surgeries for epilepsy yielded thirty-three SLAs and twenty-one resections with a mean of 21.7-month and 21.3-month follow-up, respectively. The temporal lobe was the most common target for SLA (92.6%) and resection (75%). A discrete lesion was present on brain magnetic resonance imaging (MRI) in 27/32 (84.4%) of SLA patients compared with 7/20 (35%) of resection patients with a normal MRI. Overall, 55-60% of patients became seizure-free (SF). Four of five patients with initial failure to SLA became SF with subsequent resection surgery. Complications were more frequent with resection although SF outcomes did not differ (Chi square; p=0.79). Stereotactic laser ablation patients were older than those with resections (47.0years vs. 35.4years, p=0.001). The mean length of hospitalization prior to discharge was shorter for SLA (1.18days) compared with open resection (3.43days; SD: 3.16 days) (p=0.0002). CONCLUSION: We now use SLA as a first line therapy at our center in patients with lesional temporal lobe epilepsy (TLE) before resection. Seizure-free outcome with SLA and resection was similar but with a shorter length of stay. Long-term follow-up is recommended to determine sustained SF status from SLA.

Neuropsychological outcomes following stereotactic laser amygdalohippocampectomy.

OBJECTIVE: The objective was to analyze neuropsychological testing data from 15 patients before and after stereotactic laser ablation surgery for temporal lobe epilepsy and to describe the seizure outcomes after stereotactic laser ablation surgery. METHODS: A retrospective review of 15 patients who underwent stereotactic laser ablation and who also underwent neuropsychological testing before and after surgery was performed. Verbal and visual memory was assessed in all 15 patients using California Verbal Learning Test and Wechsler Memory Scale IV. Naming was assessed in 9 of 15 patients using the Boston Naming Test. Statistical analysis was performed to determine clinically significant changes using previously validated reliable change indices and proprietary Advanced Clinical Solutions software. Seizure outcome data were evaluated using Engel classification. RESULTS: Postsurgery neuropsychological evaluation demonstrated that all 15 patients experienced at least 1 clinically significant decline in either verbal or visual memory. Ten patients in this series, including five with dominant-hemisphere surgery, demonstrated decline in delayed memory for narrative information (Logical Memory II). By contrast, the Boston Naming Test demonstrated more favorable results after surgery. Two of nine patients demonstrated a clinically significant increase in naming ability, and only one of nine patients demonstrated a clinically significant decline in naming ability. With at least 6months of follow-up after surgery, 33% reported seizure freedom. CONCLUSION: Stereotactic laser ablation can result in clinically significant and meaningful decline in verbal and visual memory when comparing patients to their own presurgical baseline. Naming ability, conversely, is much less likely to be impacted by stereotactic laser ablation and may improve after the procedure.

Neurocognitive outcome following stereotactic laser ablation in two patients with MRI-/PET+ mTLE.

The most effective treatment for drug-resistant seizures associated with mesial temporal lobe epilepsy (mTLE) is surgical resection. Neurocognitive sequelae may occur and are especially likely to occur after left temporal lobectomy. Smaller resections observed with selective amygdalohippocampectomy have resulted in a more favorable neurocognitive outcome in some cases when compared to standard anterior temporal lobectomy. Specifically, MRI-guided interstitial laser thermal ablation (MRgLITT) uses a superselective stereotactic amygdalohippocampotomy that has been reported to preserve object recognition and naming abilities compared with standard temporal lobe resection. We report two patients with drug-resistant mTLE and a normal high-resolution 3-T brain MRI who underwent neuropsychological assessment pre- and postleft temporal MRgLITT. Both patients demonstrated preserved visual naming ability following surgery. Semantic verbal fluency declined after surgery, but the magnitude of decline did not reach the statistical threshold for reliable change. Both patients demonstrated statistically significant and clinically meaningful declines in memory, but abilities across other nonmemory neurocognitive domains (i.e., visuospatial ability, attention) were preserved.

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.

Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers.

The evolution of fungicide resistance.

Fungicides are widely used in developed agricultural systems to control disease and safeguard crop yield and quality. Over time, however, resistance to many of the most effective fungicides has emerged and spread in pathogen populations, compromising disease control. This review describes the development of resistance using case histories based on four important diseases of temperate cereal crops: eyespot (Oculimacula yallundae and Oculimacula acuformis), Septoria tritici blotch (Zymoseptoria tritici), powdery mildew (Blumeria graminis), and Fusarium ear blight (a complex of Fusarium and Microdochium spp). The sequential emergence of variant genotypes of these pathogens with reduced sensitivity to the most active single-site fungicides, methyl benzimidazole carbamates, demethylation inhibitors, quinone outside inhibitors, and succinate dehydrogenase inhibitors illustrates an ongoing evolutionary process in response to the introduction and use of different chemical classes. Analysis of the molecular mechanisms and genetic basis of resistance has provided more rapid and precise methods for detecting and monitoring the incidence of resistance in field populations, but when or where resistance will occur remains difficult to predict. The extent to which the predictability of resistance evolution can be improved by laboratory mutagenesis studies and fitness measurements, comparison between pathogens, and reconstruction of evolutionary pathways is discussed. Risk models based on fungal life cycles, fungicide properties, and exposure to the fungicide are now being refined to take account of additional traits associated with the rate of pathogen evolution. Experimental data on the selection of specific mutations or resistant genotypes in pathogen populations in response to fungicide treatments can be used in models evaluating the most effective strategies for reducing or preventing resistance. Resistance management based on robust scientific evidence is vital to prolong the effective life of fungicides and safeguard their future use in crop protection.

Evaluation of memory endophenotypes for association with CLU, CR1, and PICALM variants in black and white subjects.

BACKGROUND: Genetic variants at the CLU, CR1, and PICALM loci associate with risk for late-onset Alzheimer's disease (LOAD) in genomewide association studies. In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in black and white subjects. METHODS: We pursued an association study between single nucleotide polymorphism genotypes at the CLU, CR1, and PICALM loci and memory endophenotypes. We assessed black subjects (AA series: 44 with LOAD and 224 control subjects) recruited at Mayo Clinic Florida and whites recruited at Mayo Clinic Minnesota (RS series: 372 with LOAD and 1690 control subjects) and Florida (JS series: 60 with LOAD and 529 control subjects). Single nucleotide polymorphisms at the LOAD risk loci CLU (rs11136000), CR1 (rs6656401, rs3818361), and PICALM (rs3851179) were genotyped and tested for association with Logical Memory immediate recall, Logical Memory delayed recall, Logical Memory percent retention, Visual Reproduction immediate recall, Visual Reproduction delayed recall, and Visual Reproduction percent retention scores from the Wechsler Memory Scale-Revised using multivariable linear regression analysis, adjusting for age at exam, sex, education, and apolipoprotein E ε4 dosage. RESULTS: We identified nominally significant or suggestive associations between the LOAD-risky CR1 variants and worse Logical Memory immediate recall scores in blacks (P = .068-.046, ß = -2.7 to -1.2). The LOAD-protective CLU variant is associated with better logical memory endophenotypes in white subjects (P = .099-.027, ß = 0.31-0.93). The CR1 associations persisted when the control subjects from the AA series were assessed separately. The CLU associations appeared to be driven by one of the white series (RS) and were also observed when the control subset from RS was analyzed. CONCLUSION: These results suggest for the first time that LOAD risk variants at CR1 may influence memory endophenotypes in blacks. In addition, the CLU LOAD-protective variant may confer enhanced memory in whites. Although these results would not remain significant after stringent corrections for multiple testing, they need to be considered in the context of the LOAD associations with which they have biological consistency. They also provide estimates for effect sizes on memory endophenotypes that could guide future studies. The detection of memory effects for these variants in clinically normal subjects, implies that these LOAD risk loci might modify memory prior to clinical diagnosis of AD.

Prothioconazole and prothioconazole-desthio activities against Candida albicans sterol 14-α-demethylase.

Prothioconazole is a new triazolinthione fungicide used in agriculture. We have used Candida albicans CYP51 (CaCYP51) to investigate the in vitro activity of prothioconazole and to consider the use of such compounds in the medical arena. Treatment of C. albicans cells with prothioconazole, prothioconazole-desthio, and voriconazole resulted in CYP51 inhibition, as evidenced by the accumulation of 14α-methylated sterol substrates (lanosterol and eburicol) and the depletion of ergosterol. We then compared the inhibitor binding properties of prothioconazole, prothioconazole-desthio, and voriconazole with CaCYP51. We observed that prothioconazole-desthio and voriconazole bind noncompetitively to CaCYP51 in the expected manner of azole antifungals (with type II inhibitors binding to heme as the sixth ligand), while prothioconazole binds competitively and does not exhibit classic inhibitor binding spectra. Inhibition of CaCYP51 activity in a cell-free assay demonstrated that prothioconazole-desthio is active, whereas prothioconazole does not inhibit CYP51 activity. Extracts from C. albicans grown in the presence of prothioconazole were found to contain prothioconazole-desthio. We conclude that the antifungal action of prothioconazole can be attributed to prothioconazole-desthio.

Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72.

Numerous kindreds with familial frontotemporal dementia and/or amyotrophic lateral sclerosis have been linked to chromosome 9, and an expansion of the GGGGCC hexanucleotide repeat in the non-coding region of chromosome 9 open reading frame 72 has recently been identified as the pathogenic mechanism. We describe the key characteristics in the probands and their affected relatives who have been evaluated at Mayo Clinic Rochester or Mayo Clinic Florida in whom the hexanucleotide repeat expansion were found. Forty-three probands and 10 of their affected relatives with DNA available (total 53 subjects) were shown to carry the hexanucleotide repeat expansion. Thirty-six (84%) of the 43 probands had a familial disorder, whereas seven (16%) appeared to be sporadic. Among examined subjects from the 43 families (n = 63), the age of onset ranged from 33 to 72 years (median 52 years) and survival ranged from 1 to 17 years, with the age of onset <40 years in six (10%) and >60 in 19 (30%). Clinical diagnoses among examined subjects included behavioural variant frontotemporal dementia with or without parkinsonism (n = 30), amyotrophic lateral sclerosis (n = 18), frontotemporal dementia/amyotrophic lateral sclerosis with or without parkinsonism (n = 12), and other various syndromes (n = 3). Parkinsonism was present in 35% of examined subjects, all of whom had behavioural variant frontotemporal dementia or frontotemporal dementia/amyotrophic lateral sclerosis as the dominant clinical phenotype. No subject with a diagnosis of primary progressive aphasia was identified with this mutation. Incomplete penetrance was suggested in two kindreds, and the youngest generation had significantly earlier age of onset (>10 years) compared with the next oldest generation in 11 kindreds. Neuropsychological testing showed a profile of slowed processing speed, complex attention/executive dysfunction, and impairment in rapid word retrieval. Neuroimaging studies showed bilateral frontal abnormalities most consistently, with more variable degrees of parietal with or without temporal changes; no case had strikingly focal or asymmetric findings. Neuropathological examination of 14 patients revealed a range of transactive response DNA binding protein molecular weight 43 pathology (10 type A and four type B), as well as ubiquitin-positive cerebellar granular neuron inclusions in all but one case. Motor neuron degeneration was detected in nine patients, including five patients without ante-mortem signs of motor neuron disease. While variability exists, most cases with this mutation have a characteristic spectrum of demographic, clinical, neuropsychological, neuroimaging and especially neuropathological findings.

Age-Specific Barriers and Facilitators to Research Participation Amongst African Americans in Observational Studies of Memory and Aging.

BACKGROUND: Black/African Americans experience a high burden of Alzheimer disease and related dementias yet are critically underrepresented in corresponding research. Understanding barriers and facilitators to research participation among younger and older African Americans is necessary to inform age-specific strategies to promote equity in studies of early- and late-onset neurodegenerative diseases. STUDY DESIGN: Survey respondents (n = 240) rated barriers and facilitators of research participation. Age-specific differences were evaluated using nonparametric Kruskal-Wallis tests across respondents aged 18-44 years (n = 76), 45-64 years (n = 83), and ≥ 65 years (n = 81). Strategies to mitigate barriers and promote facilitators were further explored via community-based focus groups. Pooled frequency of common themes discussed in focus groups were evaluated and compared across different ages including ≥ 45 years, ≥ 65 years, and mixed ages ≥ 45 years. RESULTS: Younger respondents (aged 18-44 and 45-64 years) expressed a greater need for flexibility in when, where, and how research testing takes place versus adults ≥ 65 years. Focus groups emphasized long-lasting consequences of systemic racism and the need to build and foster trust to resolve barriers and promote research engagement amongst African Americans. DISCUSSION: Age-specific strategies are needed to increase engagement, address recruitment disparities, and promote retention of African American participants in memory and aging studies across the lifespan.

Creating a Dementia Friendly Community in an African American Neighborhood: Perspectives of People Living with Dementia, Care Partners, Stakeholders, and Community Residents.

A dementia friendly community allows people with dementia and their care partners to remain engaged in their community well into the disease. This study presents the results of primary research aimed at exploring perceptions regarding building a dementia friendly community in an African American neighborhood in northeast Florida. Twelve focus groups and five interviews were conducted with people living with dementia, informal and formal care partners, community stakeholders and neighborhood residents, and analyzed using a grounded theory approach. Three main themes emerged from the analyses, including (1) perceived needs, (2) facilitators and barriers to being dementia friendly, and (3) opportunities for the community to become more dementia friendly. Study findings highlight the unique needs of a single African American neighborhood and the importance of culturally tailoring the dementia friendly model to diverse communities.

Reliable change on the Boston naming test.

Serial assessments are commonplace in neuropsychological practice and used to document cognitive trajectory for many clinical conditions. However, true change scores may be distorted by measurement error, repeated exposure to the assessment instrument, or person variables. The present study provides reliable change indices (RCI) for the Boston Naming Test, derived from a sample of 844 cognitively normal adults aged 56 years and older. All participants were retested between 9 and 24 months after their baseline exam. Results showed that a 4-point decline during a 9-15 month retest period or a 6-point decline during a 16-24 month retest period represents reliable change. These cutoff values were further characterized as a function of a person's age and family history of dementia. These findings may help clinicians and researchers to characterize with greater precision the temporal changes in confrontation naming ability.