Butler Hospital Research Articles

Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer’s disease

BackgroundWith the approval of disease-modifying treatments (DMTs) for early Alzheimer’s disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-β (Aβ) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP).MethodsIn this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific and BioFINDER-2 training data, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aβ-PET/CSF testing as the standard of truth.ResultsPotential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aβ-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aβ positivity in potential DMT candidates (AUC = 0.97 [0.92–1]), with diagnostic accuracy ranging from 0.88 (0.76–0.95, p = 0.028) to 0.96 (0.86–1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required confirmatory testing.ConclusionsThis study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aβ-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.

Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer's disease.

With the approval of disease-modifying treatments (DMTs) for early Alzheimer's disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-β (Aβ) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP). In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific training data and BioFINDER-2, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aβ-PET/CSF testing as the standard of truth. Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aβ-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aβ positivity in potential DMT candidates (AUC = 0.97 [0.92-1]), with diagnostic accuracy ranging from 0.88 (0.76-0.95, p = 0.028) to 0.96 (0.86-1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required from confirmatory testing. This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aβ-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.

Remote and in‐clinic digital cognitive screening tools outperform the MoCA to distinguish cerebral amyloid status among cognitively healthy older adults

AbstractBackgroundExisting cognitive screening measures fall short in capturing preclinical AD, and cognitive impairment is unrecognized or misdiagnosed in 27‐81% of older adult primary care patients. Digital assessment technology has the potential to deliver more efficient and sensitive cognitive screening, but requires rigorous validation first. We aimed to determine the accuracy of remote (M2C2 mobile app) and clinic‐based (TabCAT and DCTclockTM) digital tests to distinguish between older adults with and without AD pathologic change. We used the Montreal Cognitive Assessment (MoCA) as a reference standard comparison test.MethodWe recruited 73 cognitively normal participants with Aß PET status (Aß+, n = 25; Aß‐, n = 48, determined by clinical read) from the Butler Hospital Alzheimer’s Prevention Registry (mean age = 69.2 and education = 16.5; 71% female; 89% White). Participants completed M2C2 tasks at home 3 times per day for 8 days, followed by the TabCAT tasks, DCTclockTM, and MoCA at an in‐person study visit. We calculated the area under the curve (AUC) to compare cognitive task accuracy to distinguish Aß status. Multi‐day learning curves were used to examine differences in M2C2 task performance by Aß status over time.ResultAmong the M2C2 tasks, average performance on the Prices task (episodic memory) over 8 days showed the highest accuracy (AUC = .77) to distinguish Aß status. The Aß+ group tended to perform worse than the Aß‐ group on the Prices task over time (Figure 1). On in‐person screening measures (single time‐point), accuracy to distinguish Aß was greatest for the TabCAT Favorites task (AUC = .76), relative to the DCTclockTM (AUC = .72) and the MoCA (AUC = .71).ConclusionWe showed that several brief digital screening approaches (memory‐specific tasks on the M2C2 and TabCAT) outperform the MoCA in distinguishing between cognitively healthy individuals with and without elevated cerebral Aβ. Although further validation in community and clinic‐based samples is needed, these results suggest that these digital cognitive assessments may be suitable for more widespread screening to detect early pathological changes in neurodegenerative disorders. Figure 1. M2C2 task performance over time (3 sessions daily for 8 days) by Aβ status.

Initial experiences with amyloid‐related imaging abnormalities in patients receiving aducanumab following accelerated approval

AbstractBackgroundAducanumab is the first approved amyloid‐lowering immunotherapy for Alzheimer’s disease (AD). There is little real‐world data to guide the management of amyloid‐related imaging abnormality (ARIA), a potentially serious side‐effect requiring surveillance with serial magnetic resonance imaging (MRI). The current study seeks to characterize the symptoms, clinical course and management of ARIA in memory clinic patients treated with aducanumab.MethodWe conducted a non‐blinded, observational case series of patients who received aducanumab from June 16, 2021 to August 1, 2022 at the Butler Hospital Memory and Aging Program. Inclusion: (1) Clinical diagnosis of mild cognitive impairment (MCI) or mild dementia due to AD, (2) confirmed amyloid positivity (PET/CSF), and (3) Mini Mental State Exam (MMSE) = 20‐30. Exclusions: (1) MRI with &gt; 4 microhemorrhages, &gt; 1 area of superficial siderosis or significant cerebrovascular disease, (2) MRI contraindication, (3) anticoagulation and (4) unstable medical/psychiatric conditions. Participants received monthly aducanumab infusions, titrated to a dose of 10 mg/kg, with ApoE genotyping and enhanced MRI monitoring adapted from the phase 3 trials. The primary outcome of the study was the identification of ARIA‐E by MRI. Secondary outcomes included severity of ARIA, clinical course, and time to resolution.ResultOut of 24 patients treated with aducanumab, we identified ARIA‐E in 6 patients (25%), all ApoE‐ε4 carriers, and 4 of whom had moderate‐severe radiographic severity. Comorbid ARIA‐H occurred in 3 patients, 1 of whom also had new onset of cerebellar metastatic cancer. Symptomatic ARIA occurred in 3 patients and included headache, confusion, gait instability, and word‐finding difficulties. Treatment was discontinued in 4 cases of moderate‐severe ARIA‐E, temporarily held in 1 moderate/asymptomatic case, and dosed through in 1 mild/asymptomatic case. All cases of ARIA‐E resolved without hospitalization or corticosteroids (mean duration = 3 months, range, 1 ‐ 6 months).ConclusionAdditional amyloid‐lowering antibodies, associated with ARIA, may soon become clinically available. These data support the careful patient selection, ApoE genotyping, MRI surveillance and individualized dosing recommended in the updated FDA prescribing information and Appropriate Use Recommendations.

Remote and in‐clinic digital cognitive screening tools outperform the MoCA to distinguish cerebral amyloid status among cognitively healthy older adults

AbstractBackgroundExisting cognitive screening measures fall short in capturing preclinical AD, and cognitive impairment is unrecognized or misdiagnosed in 27‐81% of older adult primary care patients. Digital assessment technology has the potential to deliver more efficient and sensitive cognitive screening, but requires rigorous validation first. We aimed to determine the accuracy of remote (M2C2 mobile app) and clinic‐based (TabCAT and DCTclockTM) digital tests to distinguish between older adults with and without AD pathologic change. We used the Montreal Cognitive Assessment (MoCA) as a reference standard comparison test.MethodsWe recruited 73 cognitively normal participants with Aß PET status (Aß+, n = 25; Aß‐, n = 48, determined by clinical read) from the Butler Hospital Alzheimer’s Prevention Registry (mean age = 69.2 and education = 16.5; 71% female; 89% White). Participants completed M2C2 tasks at home 3 times per day for 8 days, followed by the TabCAT tasks, DCTclockTM, and MoCA at an in‐person study visit. We calculated the area under the curve (AUC) to compare cognitive task accuracy to distinguish Aß status. Multi‐day learning curves were used to examine differences in M2C2 task performance by Aß status over time.ResultsAmong the M2C2 tasks, average performance on the Prices task (episodic memory) over 8 days showed the highest accuracy (AUC = .77) to distinguish Aß status. The Aß+ group tended to perform worse than the Aß‐ group on the Prices task over time (Figure 1). On in‐person screening measures (single time‐point), accuracy to distinguish Aß was greatest for the TabCAT Favorites task (AUC = .76), relative to the DCTclockTM (AUC = .72) and the MoCA (AUC = .71).ConclusionsWe showed that several brief digital screening approaches (memory‐specific tasks on the M2C2 and TabCAT) outperform the MoCA in distinguishing between cognitively healthy individuals with and without elevated cerebral Aβ. Although further validation in community and clinic‐based samples is needed, these results suggest that these digital cognitive assessments may be suitable for more widespread screening to detect early pathological changes in neurodegenerative disorders. Figure 1. M2C2 task performance over time (3 sessions daily for 8 days) by Aβ status.

Time of day cognitive performance differences in remote, self‐administered assessments and its association with cerebral amyloidosis

AbstractBackgroundTime of day (TOD) is known to potentially influence cognition in healthy older adults. Smartphone‐based ‘burst’ testing approaches are increasingly used in AD clinical research to assess cognition across multiple timepoints. This repeated assessment approach can therefore potentially help us understand how TOD may affect different domains of cognitive functioning in normal aging and AD. This study examined the effect of TOD, and its potential interactions with cerebral amyloidosis (Aß), on remote, smartphone‐based cognitive assessment performance.MethodWe recruited 73 cognitively normal adults with elevated (Aß+, n = 25) and non‐elevated (Aß‐, n = 48) Aß positron emission tomography (PET) status from the Butler Hospital Alzheimer’s Prevention Registry (mean age = 69.29, education = 16.45, 71.2% female, 89.0% White). Participants completed brief cognitive testing sessions 3x per day for 8 days using a mobile app. We used ANOVA to examine potential differences in performance on multiple cognitive tasks by TOD (see Table 1), and linear mixed models (adjusted for age, education, and session number) to determine how TOD, Aß status, and their interaction may predict episodic memory (EM) and processing speed (PS) performance.ResultThere were main effects of both Aß status and TOD on EM, with worse performance in the Aß+ group in the afternoon (p &lt; .10 level; Est. = ‐0.05, SE = .02, p = .07), and in the evening (Est = ‐0.02, SE = .01, p = .02) relative to morning. A main effect of TOD on PS was also observed (Est. = ‐92.72, SE = 22.10, p &lt; .001). Additionally, we found an interaction between Aß status and afternoon TOD on PS (Est. = 131.05, SE = 37.76, p &lt; .001).ConclusionThese findings suggest older adults may perform worse on episodic memory tasks in the evening, regardless of Aß status. Effect of TOD on PS varied by Aß status, with Aß+ individuals performing worse in the afternoon, and Aß‐ individuals performing better in the afternoon, relative to morning. While further validation is needed, these results suggest time of day is a significant factor in remote cognitive test performance and may be moderated by AD‐related pathology.

5 Intraindividual Variability in Processing Speed on Digital Cognitive Assessments Differs by Amyloidosis Status in Cognitively Normal Older Adults

Objective:Intraindividual variability (IIV) is defined as fluctuations in an individual’s cognitive performance over time1. IIV has been identified as a marker of neurobiological disturbance making it a useful method for detecting changes in cognition among cognitively healthy individuals as well as those with prodromal syndromes2. IIV on laboratory-based computerized tasks has been linked with cognitive decline and conversion to mild cognitive impairment (MCI) and/or dementia (Haynes et al., 2017). Associations between IIV and AD risk factors including apolipoprotein (APOE) ε4 carrier status, neurodegeneration seen on brain imaging, and amyloid (Aß) Positron emission tomography (PET) scan status have also been observed1. Recent studies have demonstrated that evaluating IIV on smartphone-based digital cognitive assessments is feasible, has the capacity to differentiate between cognitively normal (CN) and MCI individuals, and may reduce barriers to cognitive assessment3. This study sought to evaluate whether such differences could be detected in CN participants with and without elevated AD risk.Participants and Methods:Participants (n=57) were cognitively normal older adults who previously received an Aß PET scan through the Butler Hospital Memory and Aging Program. The sample consisted of primarily non-Hispanic (n=49, 86.0%), White (n=52, 91.2%), college-educated (M=16.65 years), females (n=39, 68.4%). The average age of the sample was 68 years old. Approximately 42% of the sample (n=24) received a positive PET scan result. Participants completed brief cognitive assessments (i.e., 3-4 minutes) three times per day for eight days (i.e., 24 sessions) using the Mobile Monitoring of Cognitive Change (M2C2) application, a mobile app-based cognitive testing platform developed as part of the National Institute of Aging’s Mobile Toolbox initiative (Sliwinski et al., 2018). Participants completed visual working memory, processing speed, and episodic memory tasks on the M2C2 platform. Intraindividual standard deviations (ISDs) across trials were computed for each person at each time point (Hultsch et al., 2000). Higher ISD values indicate more variability in performance. Linear mixed effects models were utilized to examine whether differences in IIV existed based on PET scan status while controlling for age, sex at birth, and years of education.Results:n interaction between PET status and time was observed on the processing speed task such that Aß- individuals were less variable over the eight assessment days compared to Aß + individuals (B= -5.79, SE=2.67, p=.04). No main or interaction effects were observed on the visual working memory task or episodic memory task.Conclusions:Our finding that Aß- individuals demonstrate less variability over time on a measure of processing speed is consistent with prior work. No associations were found between IIV in other cognitive domains and PET status. As noted by Allaire and Marsiske (2005), IIV is not a consistent phenomenon across different cognitive domains. Therefore, identifying which tests are the most sensitive to early change is crucial. Additional studies in larger, more diverse samples are needed prior to widespread clinical use for early detection of AD.

28 Variability in Remote, Self-Administered Assessment Performance Associated with Self-Reported Memory Perceptions Among Older Adults

Objective:Remote assessment for cognitive screening and monitoring in the elderly has many potential advantages, including improved convenience/access and ease of repeat testing. As remote testing becomes more feasible and common, it is important to examine what factors might influence performance and adherence with these new methods. Personal beliefs about one’s ability to remember effectively have been shown to impact memory performance, especially in older adults (Lineweaver &amp; Hertzog, 1998). The perception of a low level of personal control over memory may impact a person’s use of memory strategies which might otherwise enhance performance, as well as their beliefs about the efficacy of those strategies (Lineweaver et al., 2021). The present study examined the relationship between perceived memory self-efficacy and performance and adherence on self-administered, smartphonebased remote cognitive assessments.Participants and Methods:Participants were 123 cognitively unimpaired adults (ages 55-80, 68.3% female, 87% White, M= 16.5 years of education) recruited from the Butler Hospital Alzheimer’s Prevention Registry as part of an ongoing study evaluating novel cognitive assessment methods. A cutoff of score of ≥34 on the modified Telephone Interview for Cognitive Status (TICSm) was required for enrollment. Perceived memory self-efficacy was assessed using two subscales of the Personal Beliefs about Memory Instrument (PBMI; Lineweaver et al., 1998): “prospective control”, the perception of control one currently has to influence future memory functioning, and “future control”, the perception of the amount of control over memory function one will have in the future. Participants completed three brief self-administered cognitive testing sessions per day for 8 consecutive days using a mobile app-based platform developed as part of the National Institute of Aging’s Mobile Toolbox initiative. Cognitive tasks assessed visual working memory (WM), processing speed (PS), and episodic memory (EM)(see Thompson et al., 2022).Results:Statistical analyses were conducted using univariate ANOVA tests to look for main effects of each PBMI subscale score on remote assessment adherence and average performance on each task over 8 days. After adjusting for aging, we found a higher rate of false alarms (proportion of misidentified stimuli) on the WM task was associated with higher levels of both self-reported prospective control (F(2, 86) = 4.188, p = .018) and future control (F(2, 96) = 5.003, p = .009). Increased response time on the PS task was also associated with higher levels of future control when adjusted for aging (F(2, 96) = 6.075, p = .003). There was no main effect of memory self-efficacy ratings on EM. We found no main effects of memory self-efficacy ratings on assessment adherence.Conclusions:These findings suggest perceptions of high prospective and future control are associated with positive response bias on a forced-choice WM task, and high perceptions of future control are also associated with slower response times on PS tasks. Future research should examine whether this is due to increased deliberation, cautiousness, or other factors. Limitations include the potentially limited generalizability of this largely White, highly educated, and motivated sample self-selected for AD research. Next steps for this research include comparing these results with the effects of perceived self-efficacy on in-person cognitive assessments.

Clinically Determined Asterixis Is Markedly Increased in Patients Taking Clozapine.

Department of Neurology, Butler Hospital, 345 Blackstone Blvd, Providence, RI 02906, Warren Alpert Medical School of Brown University [email protected] Conflicts of interest: Consulting: EPI-Q; Honoraria: Medlink; Karger Press. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.clinicalneuropharm.com).

The Effects of Subjective Cognitive Decline on APOE Genotype Disclosure in the Butler Hospital Alzheimer’s Prevention Registry

Subjective cognitive decline (SCD) and APOE genotyping are both instrumental in identifying high-risk individuals for Alzheimer's disease (AD) prevention trials. This study examined the relationship between SCD and the impact of APOE disclosure on the psychological and behavioral health of cognitively unimpaired individuals. Design/Setting/Participant: We recruited 189 trial volunteers (mean age 66, 65% female, 96% White), from the Butler Hospital Alzheimer's Prevention Registry. Participants completed screening for cognitive impairment and a psychological readiness assessment before learning their APOE genotype, and were followed for 6 months after. SCD had a modest, temporary impact on mood and event-related distress following APOE disclosure, specifically on those who were ε4 carriers. The presence of SCD (SCD+) did not compound the AD genetic test-specific distress related to learning that one was an ε4 carrier. SCD also did not moderate changes in perceived AD risk, with all non-carriers showing a more rapid decrease in perceived risk over time than carriers. Counterintuitively, those without SCD (SCD-) reported taking more steps in future-directives than the SCD+ group at baseline and after disclosure, potentially suggesting that those with SCD may have subtle executive declines that limit future-oriented actions or fear-avoidance behaviors. Further, the SCD- group was more accurate in recalling their APOE status and the recall accuracy correlated with their broad knowledge about APOE as a risk gene for AD. Our findings support the safety and tolerability of APOE disclosure in research volunteers regardless of their SCD statuses, but further studies are warranted to include diverse individuals and those pursuing testing through direct-to-consumer services outside of traditional research settings.

Initial Experiences with Amyloid-Related Imaging Abnormalities in Patients Receiving Aducanumab Following Accelerated Approval.

Aducanumab is the first FDA-approved amyloid-lowering immunotherapy for Alzheimer's disease. There is little real-world data to guide management of amyloid-related imaging abnormalities (ARIA), a potentially serious side-effect which requires surveillance with magnetic resonance imaging. We report our experiences in managing ARIA in patients receiving aducanumab at the Butler Hospital Memory and Aging Program during the year following FDA approval. We followed the Appropriate Use Recommendations for aducanumab to guide patient selection, detection, and management of ARIA (1). ARIA-E occurred in 6 out of 24 participants treated; all APOE-ε4 carriers. Treatment was discontinued in 4 cases of moderate-severe ARIA-E, temporarily held in 1 moderate case, and dosed through in 1 mild case (mean duration = 3 months, range, 1-6 months). No participants required hospitalization or high dose corticosteroids. Participants on anticoagulation were excluded and no macrohemorrhages occurred. These data support the measured approaches to treatment outlined in the Appropriate Use Recommendations.

Longitudinal post-shunt outcomes in idiopathic normal pressure hydrocephalus with and without comorbid Alzheimer's disease.

Alzheimer's disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity. Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24-60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively. There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence. iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.

Loneliness and subjective cognitive impairment in preclinical Alzheimer’s disease and healthy aging

AbstractBackgroundLoneliness is associated with increased dementia risk, and greater amyloid‐β (Aβ) and tau accumulation in cognitively normal older adults. However, the potential for loneliness to influence cognitive dysfunction during the preclinical disease stage has not yet been examined. Subjective cognitive complaints are an early indicator of cognitive dysfunction in Alzheimer’s disease, and may provide a sensitive endpoint to evaluate the influence of loneliness during the preclinical disease stage. This study evaluated the relationships between loneliness, subjective cognition, and Aβ status in cognitively unimpaired older adults.MethodParticipants were 112 older adults aged 60–81 years (68% female, 89% White) recruited from the Butler Hospital Alzheimer’s Prevention Registry (BAPR). A cut off score of ≥34 on a modified Telephone Interview for Cognitive Status (TICSm) was used to establish unimpaired cognition. All participants completed the 3‐item version of the UCLA Loneliness Scale and the Cognitive Function Index (CFI) to assess loneliness and subjective cognition respectively. At the time of this analysis, a subsample (n = 63) had also undergone PET neuroimaging for classification of Aß status, of which 40% were classified as Aß+.ResultOf the total sample, 28% reported mild‐moderate levels of loneliness, and another 8% reported severe loneliness. Subjective cognitive function was significantly associated with loneliness group, H(2) = 6.66, p = .036, with post hoc analyses indicating a significant trend for subjective cognitive complaints to increase with loneliness severity. Among the PET subsample, there was no significant difference observed between Aß groups in level of loneliness (p = .754) or subjective cognition (p = .852). However, there was a significant association between Aß status and loneliness group (p = .023), with Aß+ individuals being more likely to a be severely lonely (12%, n = 3) relative to the Aß‐ group (0%, n = 0).ConclusionThe results of this study highlight the potential for loneliness to be involved in the preclinical stages of AD by demonstrating associations with both subjective cognitive function and Aß status. Prospective investigations are needed to further disentangle whether loneliness may be an indicator of, or a risk factor for, emerging disease.

Lifestyle Psychiatry.

UEBELACKER: Department of Psychiatry and Human Behavior, Brown University; Alpert Medical School of Brown University; and Butler Hospital, Providence, RI Marcia L. Verduin, MD, Book Editor

Care Is A Basic Human Right

Care Is A Basic Human Right

Frontal Behavior Syndromes in Idiopathic Normal Pressure Hydrocephalus as a Function of Alzheimer's Disease Biomarker Status.

Cognitive impairment and apathy are well-documented features of idiopathic normal pressure hydrocephalus (iNPH). However, research examining other neuropsychiatric manifestations of iNPH is scant, and it is unknown whether the neuropsychiatric presentation differs for iNPH patients with comorbid Alzheimer's disease (AD) versus iNPH without AD. This study aims to advance our understanding of neuropsychiatric syndromes associated with iNPH. Fifty patients from Butler Hospital's Normal Pressure Hydrocephalus Clinic met inclusion criteria. Caregiver ratings on the Frontal Systems Behavior Scale (FrSBe) were examined to appraise changes in apathy, executive dysfunction, and disinhibition. Patients also completed cognitive tests of global cognition, psychomotor speed, and executive functioning. AD biomarker status was determined by either amyloid-beta (Aβ) positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) total tau to Aβ-42 ratio. Results revealed clinically significant elevations on the FrSBe's apathy and executive dysfunction scales and modest correlations among these scales and cognitive measures. Of the 44 patients with available neuroimaging or CSF draw data, 14 presented with comorbid AD. Relative to the iNPH-only group, the iNPH + AD group showed a larger increase from pre-illness to current informant ratings on the executive dysfunction scale, but not the apathy or disinhibition scales. These results replicate and extend prior research by identifying apathy and executive dysfunction as prominent neuropsychiatric symptoms of iNPH and suggest comorbid AD exacerbates dysexecutive behaviors. Future research is warranted to examine the effects of comorbid AD pathology in response to shunt surgery for iNPH, neuropsychiatric symptom changes, and resultant caregiver burden.

Correspondence; Revisiting H. P. Lovecraft

135 he package never properly arrived.Instead,there was a brown note stuck to my front door saying that it couldn’t be delivered. When I recovered it from the post office, the box was shipwrecked, cardboard burst and buckled. Inside, some of the books had turned to pulp; others had been soaked and slowly dried, their pages curled arthritically. Tucked among them was a green folder, the papers within damp but legible. I’d mailed the box to my home in Brookline, Massachusetts, from my parents’ house in the suburbs of Hull, the industrial city in East Yorkshire where I grew up. Twenty years earlier, I had come to the U.S. for graduate school, met my future wife, and stayed. These days, I teach philosophy at MIT. The house my essay Correspondence Revisiting H. P. Lovecraft Kieran Setiya T 136 | Kieran Setiya parents live in now is not my childhood home. But there is a room in it that they call mine, where the relics of my life sink beneath the sediment of theirs. On my last visit, I had mined the box’s contents from the bottom drawer of a dresser filled with books and papers dating from my teen infatuation with the author H. P. Lovecraft, who fused horror with sci-­ fi in “The Call of Cthulhu” and other stories. For more than a year after it came, the folder lay unopened on my bedside table. I would glance at it occasionally, sidelong, as if it held some terrible secret, like a forbidden book in one of Lovecraft’s tales. Of course I knew in outline what the documents were. But when I tried to recall the passion that went into them, the dedication of weeks and months absorbed in Lovecraft’s work, I met an almost total blank. There was a void where memory should have been. For the most part, I am happy not to think about my childhood; those are years I am glad to have left behind. A lot of what I can recall I wish I could forget. What I want now to remember, I cannot : the liberating fervor of obsession. Reading Lovecraft changed my life. I was a solitary, introspective child. Through Lovecraft, I escaped into melodrama: a myth of alien beings whose capacities dwarf our own and whose intentions threaten all of life on earth. And I found a way into philosophy. Lovecraft used the trappings of pulp fiction to philosophical ends. He wrote allegories of human insignificance, of the limits of knowledge, of mechanism and a world without purpose. These were problems in which I was already, inarticulately, lost. It was as if he could read my mind. howard phillips lovecraft was born in providence, Rhode Island, August 20, 1890, in the house of his maternal grandfather. His childhood reads like the blueprint for an author of weird fiction : an attic library of old books; a father who goes insane and winds up in a lunatic asylum; a mother so protective that she monitors her one son’s every move, so doting she believes he will be “a poet of the highest order,” so critical she tells him he is physically Correspondence | 137 repulsive. The child is, of course, a prodigy, but a high school dropout; he has a nervous breakdown. A decade later, the mother goes insane and is sent to the same asylum where the father died; she dies there, too. We don’t know how much Lovecraft knew about his father. Winfield Lovecraft was a commercial traveler for a Providence silversmith . When Lovecraft was three, Winfield was diagnosed with “general paresis”—known to us now as syphilis, which in its tertiary stage can lead to madness. He would remain in Butler Hospital until his death five years later. Was all of this kept from his young son? Or did the child witness symptoms of insanity, erratic behavior , changes in personality? “The oldest and strongest emotion of mankind is fear,” Lovecraft would later write, “and the oldest and strongest kind of fear is fear of the unknown.” The boy was a precocious reader, graduating around age five from Grimms’ Fairy Tales and the Arabian Nights to...

APA’s 13 Founders Were Dedicated to Specialty Still Trying to Find its Way

APA’s 13 Founders Were Dedicated to Specialty Still Trying to Find its Way

He Wanted the Moon: The Madness and Medical Genius of Dr. Perry Baird, and His Daughter’s Quest to Know Himby Mimi Baird, with Eve Claxton; New York, Crown Publishing, 2015, 250 pages

Back to table of contents Previous article Next article Book ReviewsFull AccessHe Wanted the Moon: The Madness and Medical Genius of Dr. Perry Baird, and His Daughter’s Quest to Know HimJeffrey L. Geller, M.D., M.P.H.Jeffrey L. GellerSearch for more papers by this author, M.D., M.P.H.Published Online:3 Oct 2016https://doi.org/10.1176/appi.ps.671006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail by Mimi Baird, with Eve Claxton; New York, Crown Publishing, 2015, 250 pagesIn He Wanted the Moon, Mimi Baird sets out to tell the story of her father. In 1944, when Mimi Baird was six years old, her father, Perry, stopped coming home, for reasons never explained to her as a child. Perry Baird had been admitted that year to Westborough State Hospital (WSH) in Massachusetts, the fourth hospital to which he had been admitted for manic episodes. He was 41 years old, stayed in the hospital 95 days, and never rejoined the family. Her father was always a mystery to Mimi, until she inherited the manuscript for a book he never finished that recounts his experiences with bipolar disorder.Ms. Baird has created a first-person account that speaks from three perspectives: her father’s, that of the psychiatric hospital medical records, and her own. One unfortunate shortcoming of the book is that Ms. Baird writes well (with the assistance of Eve Claxton) and has interesting observations to share, whereas her father’s writing makes a lot of detours before getting to cogent or engaging points.The medical records are quite interesting, providing the reader glimpses of psychiatric treatment in the 1930s–1940s. Interventions tried with Perry Baird included, for example, an 11-day narcosis treatment using sodium amobarbital. He provides views of other treatments of that era, for example, “constant restraint,” which was the maintenance of restraint that alternated between straightjackets and cold packs. Perry Baird experienced much of his treatment as “torture” devised by “state hospital psychiatrists.”Historical figures in psychiatry make their appearance. Dr. Baird came from a family of means, and he was able to get a specially arranged consultation. Harry Solomon, who was superintendent of the Boston Psychopathic Hospital and who subsequently became the Massachusetts Commissioner of Mental Health, came to see him at WSH. Dr. Solomon opined, “The manic does not know what he is doing,” and Perry Baird’s response was “Even a man of distinction, experience and education could fail to understand the manic.”Perry Baird was transferred from WSH to Balpate Hospital, a private psychiatric hospital, where his attending psychiatrist was a friend and colleague. He lasted there but two weeks. His property destruction and threats to nursing staff were too much for the private hospital, and he was sent back to WSH. Three weeks after his return to WSH, Perry Baird was notified that his license to practice medicine had been revoked.Perry Baird had a great disdain for the treatment he received at WSH: “WSH and other places like it have nothing to offer; nothing but a jail-like incarceration, brutality, and ugliness. The patients who come here recover not because of the treatment they receive, but in spite of it. Some are submerged by it, die of it.” After about one month of this final WSH admission, Perry Baird gets his freedom by escaping.Perry Baird tried and failed to connect with earlier acquaintances. He tried and failed to connect with his daughter, Mimi. He described his feelings of being victimized by stigma against people with a mental illness. He found refuge in alcohol. He died alone in a hotel room in Detroit at the age of 55.The better part of the book is Mimi Baird speaking of her life, which constitutes the last one-third of the book. It turns out Mimi’s mother had the same experience as she did—a father with bipolar disorder who left the family when his daughter was a child (in this earlier instance the daughter was ten, and her father spent the rest of his life in Norristown State Hospital). Part of Mimi Baird’s story is her quest to put together her father’s life—hospitalizations at Boston Psychopathic Hospital and Butler Hospital before the admittance to WSH and later, Galveston State Hospital. Ms. Baird learns that her father, a dermatologist, made a quite significant contribution to the psychiatric literature. I suggest you check it out: http://journals.lww.com/jonmd/citation/1944/04000/biochemical_component_of_the_manic_depressive.3.aspx.And then get a copy of He Wanted the Moon. There’s a lot more here than in many first-person accounts.Dr. Geller is the medical director at Worcester Recovery Center and Hospital, Worcester, Massachusetts, and he is editor of the Book Reviews section.The reviewer reports no financial relationships with commercial interests. FiguresReferencesCited byDetailsCited byNone Volume 67Issue 10 October 01, 2016Pages e12-e13 Metrics PDF download History Published online 3 October 2016 Published in print 1 October 2016

Physical Activity as an Intervention for Antenatal Depression: Rationale for Developing Tailored Exercise Programs for Pregnant Women with Depression.

Journal of Midwifery & Women's HealthVolume 60, Issue 5 p. 479-482 Commentary Physical Activity as an Intervention for Antenatal Depression: Rationale for Developing Tailored Exercise Programs for Pregnant Women with Depression Cynthia L. Battle PhD, Corresponding Author Cynthia L. Battle PhDAddress correspondence to Cynthia L. Battle, PhD, Butler Hospital Psychosocial Research Program, 345 Blackstone Boulevard, Providence, RI 02906. E-mail: [email protected]Search for more papers by this authorAna M. Abrantes PhD, Ana M. Abrantes PhDSearch for more papers by this authorCasey A. Schofield PhD, Casey A. Schofield PhDSearch for more papers by this authorMorganne A. Kraines BA, Morganne A. Kraines BASearch for more papers by this author Cynthia L. Battle PhD, Corresponding Author Cynthia L. Battle PhDAddress correspondence to Cynthia L. Battle, PhD, Butler Hospital Psychosocial Research Program, 345 Blackstone Boulevard, Providence, RI 02906. E-mail: [email protected]Search for more papers by this authorAna M. Abrantes PhD, Ana M. Abrantes PhDSearch for more papers by this authorCasey A. Schofield PhD, Casey A. Schofield PhDSearch for more papers by this authorMorganne A. Kraines BA, Morganne A. Kraines BASearch for more papers by this author First published: 07 April 2015 https://doi.org/10.1111/jmwh.12271Citations: 7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume60, Issue5September/October 2015Pages 479-482 ACNM Members ACNM Members: Click here to log in RelatedInformation