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Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic’s impact on social function in mild cognitive impairment and mild dementia
- Sumiyo Umeda, Hideki Kanemoto, Maki Suzuki, Tamiki Wada, Takashi Suehiro, Kyosuke Kakeda, Yoshitaka Nakatani, Yuto Satake, Maki Yamakawa, Fuyuki Koizumi, Daiki Taomoto, Sakura Hikida, Natsuho Hirakawa, Andrew Sommerlad, Gill Livingston, Mamoru Hashimoto, Kenji Yoshiyama, Manabu Ikeda
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- Journal:
- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 11 March 2024, pp. 1-14
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Objectives:
We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic.
Design:We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020–March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6–8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions.
Setting:The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan.
Participants:103 dyads of patients and caregivers.
Measurements:SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale.
Results:The scale’s interrater reliability was excellent and test–retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, “communication with others,” significantly improved at 6–8 months of follow-up.
Conclusions:The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.
1 - Physician Heal Thyself
- Daniel Gibbs, Emeritus of Oregon Health and Science University
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- Dispatches from the Land of Alzheimer's
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- 19 January 2024
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- 22 February 2024, pp 5-8
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Summary
An email with a black box warning! That’s what I got 11 years ago after Lois and I submitted saliva samples to a DNA testing service. Lois is the family genealogist, and she thought that DNA testing would be helpful in filling in some of the missing branches of our ancestral trees. In addition to lists of DNA relatives, the report included many risk genes for a variety of medical conditions, none of which were present for either of us. However, this locked black box contained two genes of neurological interest. A mutation in the LRRK-2 gene is the most common cause of hereditary Parkinson’s disease, and the APOE-4 allele is the most significant genetic risk factor for late onset Alzheimer’s disease.
9 - My Father’s “Stuff”
- Daniel Gibbs, Emeritus of Oregon Health and Science University
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- Dispatches from the Land of Alzheimer's
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- 19 January 2024
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- 22 February 2024, pp 38-42
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Summary
My father, Zack Gibbs, was 44 when I was born in 1951. He died of cancer 16 years later at age 60. Throughout his life he was a tinkerer. He liked to build things from scratch, something he got from his father who grew up on a farm. Both of them made toys for me. Unlike his father who made me things from wood, my dad loved designing and building electrical gadgets. I think he got his start in electronics from working in the 1930s as a technician for Professor Donald Menzel, the first director of the Harvard Observatory.
13 - Alzheimer’s Disease and Work
- Daniel Gibbs, Emeritus of Oregon Health and Science University
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- Dispatches from the Land of Alzheimer's
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- 19 January 2024
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- 22 February 2024, pp 56-59
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Summary
Many people can continue to work with mild cognitive impairment and sometimes even with dementia. This will depend on the requirements of the job, and the worker with cognitive impairment may need accommodation to succeed. Remarkably, there has been relatively little research on this topic.
Early prediction of mastery of a computerized functional skills training program in participants with mild cognitive impairment
- Philip D. Harvey, Courtney Dowell-Esquivel, Justin E. Macchiarelli, Alejandro Martinez, Peter Kallestrup, Sara J. Czaja
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- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 21 February 2024, pp. 1-12
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Background:
Cognition in MCI has responded poorly to pharmacological interventions, leading to use of computerized training. Combining computerized cognitive training (CCT) and functional skills training software (FUNSAT) produced improvements in 6 functional skills in MCI, with effect sizes >0.75. However, 4% of HC and 35% of MCI participants failed to master all 6 tasks. We address early identification of characteristics that identify participants who do not graduate, to improve later interventions.
Methods:NC participants (n = 72) received FUNSAT and MCI (n = 92) participants received FUNSAT alone or combined FUNSAT and CCT on a fully remote basis. Participants trained twice a week for up to 12 weeks. Participants “graduated” each task when they made one or fewer errors on all 3–6 subtasks per task. Tasks were no longer trained after graduation.
Results:Between-group comparisons of graduation status on baseline completion time and errors found that failure to graduate was associated with more baseline errors on all tasks but no longer completion times. A discriminant analysis found that errors on the first task (Ticket purchase) uniquely separated the groups, F = 41.40, p < .001, correctly classifying 94% of graduators. An ROC analysis found an AUC of .83. MOCA scores did not increase classification accuracy.
Conclusions:More baseline errors, but not completion times, predicted failure to master all FUNSAT tasks. Accuracy of identification of eventual mastery was exceptional. Detection of risk to fail to master training tasks is possible in the first 15 minutes of the baseline assessment. This information can guide future enhancements of computerized training.
Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer’s disease, Alzheimer’s disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis
- Sandeep R. Pagali, Rakesh Kumar, Allison M. LeMahieu, Michael R. Basso, Bradley F. Boeve, Paul E. Croarkin, Jennifer R. Geske, Leslie C. Hassett, John Huston III, Simon Kung, Brian N. Lundstrom, Ronald C. Petersen, Erik K. St. Louis, Kirk M. Welker, Gregory A. Worrell, Alvaro Pascual-Leone, Maria I. Lapid
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- Journal:
- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 08 February 2024, pp. 1-49
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Objective:
We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment.
Design:Systematic review, Meta-Analysis
Setting:We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.
Participants and interventions:RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.
Measurement:Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423).
Results:The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD = −0.96 [−1.32, −0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity.
Conclusion:The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.
P173: Structural Changes in the Hippocampal Subfields in Early-Onset Mild Cognitive Impairment
- Seok Woo Moon
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 02 February 2024, p. 222
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Objective:
The aim of this study was to examine the structural change in the hippocampal subfields in early-onset (EO) mild cognitive impairment (MCI) patients associated with the APOE ε4 carrier state.
Methods:This study had 50 subjects aged 55-63 years, all of whom were diagnosed with amnestic MCI at baseline via the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet (CERAD-K). The EO-MCI patients were divided into the MCI continued (MCIcont) and Alzheimer’s disease (AD) converted (ADconv) groups 2 years later. The volumes of hippocampal subfields were measured for all the subjects. The calculations were based on the change of the volumes between the 2-year-interval brain Magnetic resonance image (MRI) scans between MCIcont and ADconv groups according to the Apolipoprotein ε4 (APOE ε4) carrier state.
Results:There was a significant correlation between APOE ε4 allele and structural changes in several hippocampal subfields. The volume reduction in cornus ammonis 1 (CA1) field and subiculum, especially in the APOE ε4 carriers. The significance was more prominent in ADconv group.
Conclusion:These results suggest that the possession of APOE ε4 allele may lead to significantly greater predilection for the structural changes in hippocampal subfields, showing significant changes, especially in the ADconv patients compared with MCIcont patients.
Premorbid personality traits as predictors for incident predementia syndromes: a multistate model approach
- Morgan J. Schaeffer, Stuart W.S. MacDonald, Theone S.E. Paterson
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- Journal of the International Neuropsychological Society , First View
- Published online by Cambridge University Press:
- 29 January 2024, pp. 1-11
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Objective:
Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states.
Methods:Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded.
Results:Mann–Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI.
Conclusions:FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.
5 Cognitive Rehabilitation Using Teleneuropsychology. A Cohort Study in South America
- Carlos Martinez Canyazo, Rodrigo S Fernandez, Maria B Helou, Micaela Arruabarrena, Nicolas Corvalan, Agostina Carello, Paula Harris, Monica Feldman, Ismael Luis Calandri, Maria E Martin, Ricardo F Allegri, Lucia Crivelli
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 209
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Objective:
The COVID-19 pandemic has affected the continuity of cognitive rehabilitation (CR) worldwide. However, the use of teleneuropsychology (TNP) to provide CR has contributed significantly to the continuity of treatment. The objective of this study was to measure the effects of CR via the TNP on cognition, neuropsychiatric symptoms, and memory strategies in a cohort of patients with Mild Cognitive Impairment (MCI).
Participants and Methods:A sample of 60 patients (60% female; age: 72.4±6.96) with MCI according to Petersen criteria was randomly divided into two groups: 30 cases (treatment group) and 30 controls (waiting list group). Subjects were matched for age, sex, and MMSE or MoCA.
The treatment group received ten weekly CR sessions of 45 minutes weekly. Pre-treatment (week 0) and post-treatment (week 10) measures were assessed for both groups. Different Linear Mixed Models were estimated to test treatment effect (CR vs. Controls) on each outcome of interest over Time (Pre/Post), controlling for Diagnosis, Age, Sex, and MMSE/MoCA performance.
Results:A significant Group (Control/Treatment) x Time (pre/post) interaction revealed that the treatment group at 10 weeks had better scores in cognitive variables: memory (RAVLT learning trials p=0.030; RAVLT delayed recall p=0.029), phonological fluency(p=0.001), activities of daily living (FAQ p=0.001), satisfaction with memory performance (MMQ Satisfaction p=0.004) and use of memory strategies (MMQ Strategy p=0.00), and a significant reduction of affective symptomatology: depression (GDS p=0.00), neuropsychiatric symptoms (NPIQ p=0.045), Forgetfulness (EDO-10 p=0.00), Stress (DAS Stress p=0.00).
Conclusions:This is the first study to test CR using teleNP in South America. Our results suggest that CR through teleNP is an effective intervention to improve performance on cognitive variables and reduce neuropsychiatric symptomatology compared to patients with MCI. These results have great significance in the context of the COVID-19 pandemic in South America, where teleNP is proving to be a valuable tool.
51 Longitudinal Performance on the NIH Toolbox Cognition Module in a Cognitive Aging Sample
- Molly A Mather, Emma J Pollner, Emily H Ho, Richard Gershon, Sandra Weintraub
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 359-360
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Objective:
As the older adult population increases in the coming decades, the number of persons that develop dementia of the Alzheimer’s type (DAT) will increase accordingly. Though curative treatment for Alzheimer’s disease remains elusive, early detection of cognitive decline allows for initiation of pharmacological treatment to slow disease progression and non-pharmacological approaches to support quality of life and well-being of affected individuals and their care partners. Streamlined approaches that bridge the gap between brief screenings and comprehensive neuropsychological evaluation are needed. The NIH Toolbox Cognition Battery (NIHTB-CB) is a brief, easily administered, computerized cognitive battery that assesses various aspects of both fluid and crystallized cognitive abilities. ARMADA (Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging) is a multi-site study that aims to validate the NIHTB across the spectrum from normal aging to DAT. The current study utilized longitudinal data from ARMADA to determine whether performance on the NIHTB-CB detects cognitive decline in persons with normal cognition (NC), mild cognitive impairment (MCI), and mild DAT over the span of two years. We predicted that scores would decline for the MCI and DAT groups, but not for the NC group.
Participants and Methods:Participants were 191 participants drawn from the larger ARMADA cohort aged 65-84 (nNC = 118, nMCI = 47, nDAT = 26) that completed the NIHTB-CB at baseline and 12 months. The clinical groups were significantly older than the NC group at baseline (MNC = 72.72, MMCI = 76.63, MDAT = 75.42; p < .001) and the NC and MCI groups had significantly more years of education than the DAT group (MNC = 17.03, MMCI = 16.83, MDAT = 15.54; p = .008).
Results:Mixed model ANOVAs determined differences in uncorrected NIHTB-CB scores between clinical groups at baseline and 12 months, controlling for age and education. There were significant interactions between time and clinical group for Flanker (p < .001), Pattern Comparison (p < .001), and Picture Vocabulary (p = .001), such that the DAT group demonstrated a more negative slope of change than the NC and MCI groups. For Oral Reading, the MCI group demonstrated a more negative slope of change than the NC and DAT groups (p = .01).
Conclusions:Differential score trajectories were found for the Flanker task, with a more negative pattern of change in scores in the DAT group compared to the NC and MCI groups. Contrary to expectation, scores decreased for the two crystallized subtests across groups, which may reflect regression to the mean given high baseline scores, especially for Picture Vocabulary; however, these results were also moderated by group with less decline in scores in the NC group, which may indicate involvement of non-crystallized abilities in executing a single word comprehension task. Group differences were subtle, which may in part reflect the relatively short period of follow up. The Flanker task appears to be most sensitive to decline in mild DAT compared to MCI and NC. Results provide preliminary support for the utility of NIHTB-CB in detecting cognitive decline along the cognitive aging to DAT spectrum.
91 Agent Orange Exposure and Mild Cognitive Impairment in U.S. Vietnam Era Veterans
- Rosemary Toomey, Carol E Franz, Jeremy A Elman, Ruth E McKenzie, William S Kremen, Michael J Lyons
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 392-393
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Objective:
US forces used Agent Orange (AO) during the Vietnam War and continued to store/test it at other locations after the war. AO is a powerful herbicide including dioxin, a highly toxic ingredient classified as a human carcinogen. The National Academies of Sciences, Engineering, and Medicine periodically review the literature on the health effects of AO exposure (AOE) and concluded in 2018 that there is sufficient evidence linking AO with a wide range of adverse health outcomes, including neurologic disorders (e.g., Parkinson’s disease). The VA has a list of medical disorders considered presumptive conditions related to AOE. More recently, AOE has been linked to a nearly double risk compared to those without AOE for receiving a dementia diagnosis. To our knowledge, no one has investigated the association of AOE to mild cognitive impairment (MCI), a condition thought to precede dementia.
Participants and Methods:We examined men in three waves of the Vietnam Era Twin Study of Aging (VETSA). In wave 3, participants self-reported yes/no to the question of whether they ever had prolonged or serious AOE. MCI was diagnosed by the Jak-Bondi approach. Impairment was defined as 2+ tests within a cognitive domain that were more than 1.5 standard deviations below normative means after adjusting for premorbid cognitive ability. In mixed effects models, we tested the effect of AOE on MCI status. Models were adjusted for age, ethnicity, and non-independence within twin pairs.
Results:In wave 3, 12.6% (230) of 1167 participants reported AOE. Those with AOE data had mean ages of 51.1 (wave 1), 56.0 (wave 2), and 61.4 (wave 3). Those with data on both AOE and MCI numbered 861 (wave 1), 900 (wave 2), 1121 (wave 3), and 766 had AOE and MCI at all waves. AOE was significantly related to wave 2 MCI (p < .001), but not to waves 1 and 3 MCI. AOE was significantly associated with the number of time points at which someone met criteria for MCI (p = .011). Analyses were conducted on six cognitive domains used to diagnose MCI, using available participants per wave. At all 3 waves, AOE was significantly associated with lower scores in processing speed (p = .003, p = .004, p = .005, respectively), working memory (p < .001, p = .002, p = .008) and nearly significant at all waves for executive dysfunction (p < .001, p < .001, p = .050). There were two other significant associations [wave 2 memory (p = .038), wave 3 fluency (p = .024)]. The semantic fluency cognitive domain was unrelated to AOE in all waves.
Conclusions:AOE was consistently associated with lower processing speed, working memory, and executive dysfunction in males ages 51-61. It was also associated with the number of time points at which one met criteria for MCI in that age range, and with MCI in the mid-fifties. Findings support the idea of a risk for greater cognitive decline in those exposed to AO earlier in their lives, and with a risk for developing MCI.
43 Transcutaneous Vagus Nerve Stimulation Effects on Functional Connectivity of the Hippocampus in Mild Cognitive Impairment
- Alexandria G O'Neal, Ronald Cohen, Eric C Porges, Damon G Lamb, Aidan Murphy, Steven T DeKosky, John B Williamson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 454
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Objective:
Transcutaneous vagus nerve stimulation (tVNS) is a promising potential intervention for Alzheimer's disease (AD) due to its influence on brain functions and mechanisms important in disease progression. Regions of interest include projection to the nucleus of the solitary tract, locus coeruleus, and hippocampus. Deterioration of the hippocampus is one of the most prominent early characteristics of AD, particularly during the mild cognitive impairment (MCI) stage. tVNS could modify function of the hippocampus. We examined resting state functional connectivity from the bilateral hippocampus in response to tVNS in patients with MCI.
Participants and Methods:Fifty older adults (28 women, 60-89 years of age) diagnosed with MCI were assessed. MCI was confirmed via diagnostic consensus conference with a neurologist and neuropsychologist (sources of information: Montreal Cognitive Assessment Test [MoCA], Clinical Dementia Rating scale [CDR], Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised [HVLT-R] and medical record review). Resting state functional magnetic resonance imaging (fMRI) was collected on a 3T Siemens Prisma scanner while participants received either unilateral tVNS (left tragus, n = 25) or sham stimulation (left ear lobe, n = 25). fMRI data were processed using CONN toolbox v18b and hippocampal seed to voxel (whole brain) analyses were conducted with voxel and cluster level multiple comparison correction.
Results:Contrasting tVNS and sham stimulation, whole-brain seed-to-voxel analysis demonstrated significant changes in connectivity from the left hippocampus to several cortical and subcortical regions bilaterally. Specifically, there was increased connectivity to prefrontal regions and cingulate gyri, and decreased connectivity to anterior and medial temporal lobes. A seed-to-voxel analysis from the right hippocampus indicated significant decrease in connectivity to a single cluster of regions in the left anterior temporal lobe in response to tVNS.
Conclusions:In conclusion, tVNS modified connectivity from the hippocampus to multiple brain regions implicated in semantic and salience functions, in which disruption correlates with deterioration in AD. These findings indicate afferent target engagement of tVNS. Future work is needed to investigate the long-term effects of tVNS in patients with MCI and whether it could contribute to meaningful cognitive change and subsequent improvements in quality of life.
55 The Indirect Effect of Positive Aspects of Caregiving on the Relationship between Dementia Severity and Caregiver Burden
- Elizabeth A Cousins-Whitus, Karlee Patrick, Kimberly Chapman, Jennifer Drost, Mary Beth Spitznagel
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 261-262
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Objective:
Caregiver burden tends to worsen as severity of dementia increases, and elevated burden can lead to negative consequences for dementia caregivers. In contrast, positive aspects of caregiving, such as feelings of being useful, needed, or appreciated as a caregiver, are associated with better outcomes. Caregivers reporting fewer positive experiences robustly demonstrate greater burden, suggesting that a lack of positive aspects of caregiving could be a key component of the relationship between dementia severity and burden. This study investigated whether an indirect effect of positive aspects of caregiving would be observed on the association between dementia severity and burden.
Participants and Methods:Data were extracted from the medical records of 724 patients enrolled for services at an outpatient memory clinic. Caregiver-care recipient dyads were included based on a clinically supported patient diagnosis on the dementia spectrum following a comprehensive geriatric evaluation and having fully completed assessments from an informal caregiver. Caregivers completed the Zarit Burden Interview (ZBI) and the Positive Aspects of Caregiving (PAC) measures. The Montreal Cognitive Assessment and Mini-Mental State Exam were used to estimate dementia severity, standardized to create a single variable. Multiple potential covariates (e.g., age, gender, education, nature of dyadic relationship) were considered for inclusion in the model. A cross-sectional mediation analysis using the Hayes PROCESS macro explored presence of an indirect effect of PAC on the relationship between dementia severity and ZBI using 5000 bootstrap samples.
Results:Of the proposed covariates, only caregiver age was correlated with any of the primary variables; this variable was controlled in subsequent analyses. Significant relationships emerged between dementia severity and ZBI (r=-.12, p<.001), between PAC and ZBI (r=-.23, p<.001), and between dementia severity and PAC (r=-.07, p<.05). An indirect effect of positive aspects of caregiving on the relationship between dementia severity and ZBI was statistically significant (B= .0092, BC 95% CI [.0008, .0185]), accounting for 14.4% of the variance in the model.
Conclusions:A small but significant indirect effect of positive aspects of caregiving was observed on the association between dementia severity and burden. Results suggest that as dementia severity worsens, a caregiver who experiences greater positive aspects of caregiving will sustain less burden. Longitudinal examination of these relationships is needed to fully understand causality. Findings may help healthcare providers tailor treatment to alleviate caregiver burden.
76 Baseline Frontoparietal Gray Matter Volume Predicts Executive Function Performance at 24-Months in Early and Late Mild Cognitive Impairment
- Ann J. Lee, Scott Hayes
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 380
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Objective:
To examine the relationships between baseline gray matter volumes, diagnostic status, and executive function performance at 24-month follow-up, and the relative importance of predictors of executive function in a cohort of non-demented older adults.
Participants and Methods:The study sample included 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6, SD = 6.4; mean education = 17 years, SD = 2.4). At baseline, 49 participants were diagnosed as cognitively normal (CN), 60 as early mild cognitive impairment (EMCI), and 38 as late mild cognitive impairment (LMCI). Magnetic resonance imaging (MRI) data were collected at baseline. A composite score of executive function and FreeSurfer-derived gray matter regions-of-interest (ROI; whole brain, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, superior parietal lobule, inferior parietal lobule, hippocampus) were examined. Hierarchical linear regression models were employed to assess whether brain volume predicted executive function at 24-month follow-up and interaction effects between baseline ROI volume and diagnostic status. Age, gender, education, Mini-Mental State Examination scores, and APOE-e4 allele status were included as control variables in each model. Relative importance metrics, which quantifies an individual regressor’s contribution to a multiple regression model, were computed using the Lindemen, Merenda, and Gold (lmg) method to assess the relative contribution of each variable in predicting executive function performance.
Results:Across all participants, baseline gray matter ROI volume accounted for a significant amount of variance in executive function at 24-months after accounting for control variables. Specifically, anterior cingulate cortex and superior parietal lobule accounted for an additional 7% and 6% of variance in executive function at 24-months. Significant brain region X diagnostic status interaction effects were observed in executive function performance at 24-months. Relative importance metrics within each group indicated that age is the most important predictor of executive function at 24-months for CN, anterior cingulate cortex is most important for EMCI, and Mini-Mental Examination score is most important for LMCI.
Conclusions:Our findings implicate frontoparietal gray matter regions as significant predictors of executive function performance at 24-months, and that this relationship is moderated by diagnostic status. Our results indicate that the value of specific variables to predict executive function performance varies based on diagnostic status. Specifically, anterior cingulate cortex was a significant predictor of executive function performance across all participants and was the most important variable in predicting performance in the earliest stage of mild cognitive impairment. These results support previous studies examining gray matter correlates of executive function and extend the literature by exploring predictors of executive function in early and late stages of mild cognitive impairment.
2 Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes
- Kelsey R Thomas, Katherine J Bangen, Alexandra J Weigand, Gema Ortiz, Kayla S Walker, David P Salmon, Mark W Bondi, Emily C Edmonds
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 103-104
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Objective:
There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of <129 across subgroups.
Participants and Methods:A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score <129, by cluster group.
Results:Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p<.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p<.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score <129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p<.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p<.001) groups at greater risk of progression to a DRS score <129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS <129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).
Conclusions:Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.
5 Large-Scale Network Connectivity and Cognitive Function after Exercise Training in Older Adults
- J. Carson Smith, Kristy A. Nielson, Junyeon Won
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 674
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Objective:
Despite growing evidence regarding the association between exercise training (ET) and functional brain connectivity, little is known about the effects of ET on within- and between-network functional connectivity (FC) of core brain networks. We investigated the effects of ET on within- and between-network functional connectivity of the default mode network (DMN), frontoparietal network (FPN), and salience network (SAL) in older adults with intact cognition (CN) and older adults diagnosed with mild cognitive impairment (MCI). We further examined whether the ET-induced changes in FC were associated with changes in cognitive performance.
Participants and Methods:33 older adults (78.0±7.0 years; 16 MCI and 17 CN) participated in the present study. Before and after a 12-week walking ET intervention, participants underwent cardiorespiratory fitness tests, the Controlled Oral Word Association Test (COWAT), the Rey Auditory Verbal Learning test (RAVLT), a narrative memory test (logical memory; LM), and a resting-state fMRI scan. We examined the within- and between-network connectivity of the DMN, FPN, and SAL before and after ET. We also used linear regression to examine associations between ET-related changes in the within- and between-network connectivity and cognitive function.
Results:There were significant improvements in VO2peak, COWAT, RAVLT, and LM after ET across participants. Significant increases in within-network connectivity of the DMN and SAL were observed in response to ET across participants. FC between the DMN-FPN, DMN-SAL, and FPN-SAL were also increased after ET. Moreover, greater SAL within connectivity and FPN-SAL between connectivity were associated with enhanced LM immediate recall performance after ET. There were no significant interactions between Time (before vs after ET) and Group (CN vs MCI) for network connectivity or cognitive function.
Conclusions:Our findings suggest that increased within- and between-network connectivity following 12-weeks of walking exercise may subserve improvements in memory performance in older individuals with intact cognition and in those diagnosed with MCI.
56 Predictors of Finger Tapping Variability in Older Adults Evaluated for a Neurodegenerative Memory Disorder
- Molly M McElvogue, Lori Steffes, Anna Burke, Ashley M Stokes, George P Prigatano
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 567-568
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Objective:
Patients with early Alzheimer Disease (AD) and Mild Cognitive Impairment of the Amnestic type (MCI-A) have been reported to show large variability of tapping scores. Factors that contribute to that variability remain undetermined. This preliminary study aimed to identify predictors of finger tapping variability in older adults evaluated for a neurodegenerative memory disorder. Based on earlier research with normally functioning adults, we predicted that the number of “invalid” tapping responses (i.e. failure of the index finger to adequately lift off the tapping key once it is depressed to produce the next number on a mechanical counter) and the female gender would predict finger tapping variability, but age and educational level would not predict variability.
Participants and Methods:This preliminary study included 4 groups of participants, comprised of 8 healthy controls (HC, 3 males; 73±7years); 12 persons with subjective memory complaints (SMC, 3 males; 69±5 years); 12 with MCI-A (7 males; 76±5 years) and 7 early AD (5 males; 75±6years). All participants were administered a modified version of the Halstead Finger Tapping Test (HFTT). Mean, range of tapping score (i.e. a measure of variability), and number of invalid taps across 7 trials in each hand were calculated. ANOVA was performed for the HFTT metrics with the main effect of group. Tukey HSD tests were used for post hoc comparisons between groups. Multiple regression analysis was performed to determine the degree to which the number of invalid tapping responses, sex, age, and educational level predicted finger tapping variability using all 4 groups.
Results:Mean tapping score did not vary significantly across groups in the dominant [F (3, 35) = 0.633, p = 0.599] or non-dominant [F (3, 35) = 2.345, p = 0.090] hand. Range score approached a significant difference between groups in the dominant hand [F (3, 35) = 2.745, p = 0.058], with a clear significant effect of group on range score in the non-dominant hand [F (3, 35) = 4.078, p = 0.014]. Range score in the nondominant hand was significantly higher in the AD compared to SMC (p = 0.018) and HC (p = 0.024). Regression analysis revealed statistically significant findings for the dominant hand (R2 = 0.327, F (4, 34) = 4.130, p = 0.008) and for the non-dominant hand (R2 = 0.330, F (4, 34) = 4.180, p = 0.007). For both the dominant and non-dominant hands, number of invalid taps significantly predicted range score (ß = 0.453, p = 0.044, and ß = 0.498, p = 0.012, respectively). Sex, age, and education years did not predict range scores.
Conclusions:Variability of finger tapping in patients evaluated for neurodegenerative memory disorders and aged matched controls is predicted by the number of invalid tapping responses (comprising over 30% of the variance), but not by demographic variables in this clinical sample. Neurodegenerative disorders may eliminate a sex effect.
5 LIfestyle for BRAin Health (LIBRA) Modifiable Factors Risk Score and Concussion History Associations with Cognition in Older Former National Football League Players.
- Benjamin L Brett, Neelum T Aggarwal, Avinash Chandran, Zachary Y Kerr, Samuel R Walton, J.D. DeFreese, Kevin M Guskiewicz, Ruben J Echemendia, William P Meehan III, Michael A McCrea, Rebekah Mannix
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 305-306
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Objective:
Traumatic brain injury is one of several recognized risk factors for cognitive decline and neurodegenerative disease. Currently, risk scores involving modifiable risk/protective factors for dementia have not incorporated head injury history as part of their overall weighted risk calculation. We investigated the association between the LIfestyle for BRAin Health (LIBRA) risk score with odds of mild cognitive impairment (MCI) diagnosis and cognitive function in older former National Football League (NFL) players, both with and without the influence of concussion history.
Participants and Methods:Former NFL players, ages ≥ 50 (N=1050; mean age=61.1±5.4-years), completed a general health survey including self-reported medical history and ratings of function across several domains. LIBRA factors (weighted value) included cardiovascular disease (+1.0), hypertension (+1.6), hyperlipidemia (+1.4), diabetes (+1.3), kidney disease (+1.1), cigarette use history (+1.5), obesity (+1.6), depression (+2.1), social/cognitive activity (-3.2), physical inactivity (+1.1), low/moderate alcohol use (-1.0), healthy diet (-1.7). Within Group 1 (n=761), logistic regression models assessed the association of LIBRA scores and independent contribution of concussion history with the odds of MCI diagnosis. A modified-LIBRA score incorporated concussion history at the level planned contrasts showed significant associations across concussion history groups (0, 1-2, 3-5, 6-9, 10+). The weighted value for concussion history (+1.9) within the modified-LIBRA score was based on its proportional contribution to dementia relative to other LIBRA risk factors, as proposed by the 2020 Lancet Commission Report on Dementia Prevention. Associations of the modified-LIBRA score with odds of MCI and cognitive function were assessed via logistic and linear regression, respectively, in a subset of the sample (Group 2; n=289) who also completed the Brief Test of Adult Cognition by Telephone (BTACT). Race was included as a covariate in all models.
Results:The median LIBRA score in the Group 1 was 1.6(IQR= -1, 3.6). Standard and modified-LIBRA median scores were 1.1(IQR= -1.3, 3.3) and 2(IQR= -0.4, 4.6), respectively, within Group 2. In Group 1, LIBRA score was significantly associated with odds of MCI diagnosis (odds ratio[95% confidence interval]=1.27[1.19, 1.28], p <.001). Concussion history provided additional information beyond LIBRA scores and was independently associated with odds of MCI; specifically, odds of MCI were higher among those with 6-9 (Odds Ratio[95% confidence interval]; OR=2.54[1.21, 5.32], p<.001), and 10+ (OR=4.55;[2.21, 9.36], p<.001) concussions, compared with those with no prior concussions. Within Group 2, the modified-LIBRA score was associated with higher odds of MCI (OR=1.61[1.15, 2.25]), and incrementally improved model information (0.04 increase in Nagelkerke R2) above standard LIBRA scores in the same model. Modified-LIBRA scores were inversely associated with BTACT Executive Function (B=-0.53[0.08], p=.002) and Episodic Memory scores (B=-0.53[0.08], p=.002).
Conclusions:Numerous modifiable risk/protective factors for dementia are reported in former professional football players, but incorporating concussion history may aid the multifactorial appraisal of cognitive decline risk and identification of areas for prevention and intervention. Integration of multi-modal biomarkers will advance this person-centered, holistic approach toward dementia reduction, detection, and intervention.
79 Brief Subjective Memory Screener Predicts Memory Dysfunction
- Jillian L Joyce, Sandra Rizer, Shaina Shagalow, Leah Waltrip, Silvia Chapman, Stephanie Cosentino
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 382-383
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Objective:
Alzheimer’s disease (AD) is expected to affect over 7 million older Americans by 2025. Development of fast and inexpensive screening measures for routine screening is critical for identifying those suffering from the earliest stages of AD including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). Here we assess the validity and utility of a brief, 5-item SCD screener and its associations with neuropsychological performance as compared to an existing objective cognitive screener, the Mini Mental Status Exam (MMSE).
Participants and Methods:Development: A brief, 5-item SCD questionnaire was developed based on a more extensive 20-item version previously validated (Chapman et al. 2021). Participants: 27 cognitively diverse (MCI and cognitively normal) community dwelling older adults were recruited for this study. Mean age: 71.9 ± 7. Inclusion criteria include memory concerns. Exclusion criteria include no previous diagnoses of neurodegenerative diseases and/or major stroke. Administration: Participants completed a brief, 5-item SCD screener along with cognitive testing including the MMSE and a clinically validated list-learning test, the Selective Reminding Test (SRT). Statistical Methods: Spearman 2-tailed correlations were conducted to assess the relationship between the two screening measures, and their relationships to the SRT. Outcome measures on the SRT included total recall (max: 72) and delayed recall (max: 12). All cognitive measures were demographically adjusted with normative data.
Results:The mean total for the SCD screener was 2.1 ±1.1, and the mean MMSE score was 29.2 ± 1.2. The SCD screener was associated with MMSE scores (r= -.39, p= .043), SRT Total Recall (r= -.43, p= .024) and Delayed Recall (r=-.42, p=.031) measures. MMSE scores did not associate with either SRT outcome (p>.05).
Conclusions:Results support the utility and validity of a brief subjective cognitive decline screener for identifying those who may be experiencing memory dysfunction. The brief SCD screener outperformed the MMSE, an existing and widely used objective screening measure. Associations between the SCD screener and SRT outcomes support the validity and utility of the brief screener and recapitulate previous findings with the more extensive version of the SCD questionnaire (Chapman et al. 2021). Ongoing research is focusing on the utility of the screener in frontline clinical settings and translation of the screener into Spanish.
8 Perspectives of Self, Stigma, and the Future Following Alzheimer's Disease Biomarker Disclosure in Cognitively Symptomatic Older Adults
- Annalise Rahman-Filipiak, Mary Lesniak, Marie Milliken, Sara Feldman, J. Scott Roberts, Benjamin M Hampstead
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 219-221
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Objective:
In the absence of treatments to halt or reverse symptoms of Alzheimer's disease, early detection may extend the window for meaningful treatment, advanced planning, and coping. Positron emission tomography (PET) scans for amyloid and tau are validated biomarkers of AD, yet results are rarely disclosed to participants due to concerns about negative impacts. While prior studies suggest limited anxiety, depression, or suicidality following biomarker disclosure, no study to date has examined broader psychological impacts of PET amyloid/tau disclosure to symptomatic individuals. Therefore, we explored post-disclosure changes in future time perspective (perceptions of limited time or possibilities left in the future), self-efficacy for managing symptoms, and perceived stigma as a function of result received.
Participants and Methods:Forty-three older adults (age = 72.0±6.2 years; education = 16.5±2.6; 88.4% White Non-Hispanic; 48.8% female) participated in the study, of whom 62.8% were diagnosed with mild cognitive impairment (MCI) and the remainder with Dementia of the Alzheimer's type. All participants underwent pre-disclosure biomarker education and decisional capacity assessment, followed by baseline measures. Participants demonstration decisional capacity completed an interactive disclosure session during which they received dichotomous results of their research positron emission tomography (PET) scans for amyloid and tau (elevated versus not elevated for each biomarker). Findings were discussed in relation to presence/absence of Alzheimer's disease, the etiology of their cognitive difficulties, and risk for conversion or further decline. At baseline, immediately following disclosure, and at 1-week follow-up, participants completed several questionnaires: the Future Time Perspective (FTP) scale, a measure of how much the participant sees time as limited, the Self Efficacy for Managing Chronic Disease scale (SECD), and the Stigma Scale for Chronic Illness (SSCI-8), all of which were modified to apply to Alzheimer's disease and associated experiences.
Results:The main effects of time (F=1.10, p=.334, A?p2=.026), biomarker status (F(1)=3.10, p=.086, Ajp2=.070), and the time by biomarker status interaction (F=0.39, p=.661, Ajp2=.009) on FTP score was not significant. Though neither time (F=0.07, p=.933, A?p2=.002) nor the time by biomarker status interaction (F=2.16, p=.122, Ajp2=.050) effect on SECD was significant, being biomarker positive (A+T-/A+T+) was associated with lower self-efficacy (F(1)=5.641, p=.022, Ajp2=.121). Neither main effect for time (F=0.15, p=.853, Ajp2=.004) or biomarker status (F(1)=0.35, p=.558, A?p2=.009) on SSCI-8 was significant. The time by biomarker status interaction was significant (f=4.27, p=.018, =.096), such that biomarker negative participants experience a transient increase in perceived stigma directly after disclosure that resolves one week later, and biomarker negative participants experience the opposite pattern.
Conclusions:Findings suggest that individuals who receive biomarker positive results may feel less competent to manage their symptoms compared to those who are biomarker negative, emphasizing the need for post-disclosure interventions targeting self-efficacy. The effect of disclosure on perceptions of time being limited and on perceived stigma were minimal, even when those results indicate evidence of Alzheimer's disease and risk for clinical progression. These results further support the safety of biomarker disclosure procedures. Future studies should provide longer-term assessment of psychological, behavioral, and clinical outcomes following Alzheimer's disease biomarker disclosure.