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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.
67 Blinding and Double-Blinding of HD-tDCS in Double-Blind, Randomized Controlled Trials
- Ashley Harrie, Carine El Jamal, Michael Padgett, Annalise Rahman-Filipiak, 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. 474-475
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Objective:
High-definition transcranial direct current stimulation (HD-tDCS) is a non-invasive brain stimulation technique shown to modulate neuronal networks. In order for HD-tDCS to be used in randomized, placebo-controlled clinical trials, it is critical to have methods that enable blinding. Some research has shown that sham stimulation is an effective blind in tDCS. However, few studies have investigated the double-blinding of HD-tDCS, especially at intensities greater than 2mA. We address this knowledge gap by examining the blinding and double-blinding of HD-tDCS among a mixed neurologic sample of older adults.
Participants and Methods:A sample of 240 older adults (Mage = 72.21±8.94) with various clinical diagnoses (Normal Cognition = 34, Amnestic MCI [aMCI] = 172, Dementia-Alzheimer’s Type [DAT] = 27, Other = 7) were recruited through five double-blind, randomized controlled trials. All participants were stimulation naive at their first session and received one to thirty sessions of 20- or 30-minutes of active (n=1472) or sham (n=681) stimulation at total amplitudes of 2mA, 4mA, or 6mA. At the start of each stimulation session, a study team member entered a code into the tDCS unit, and the electrical current was gradually ramped up to the specified (blinded) amplitude over a period of 30 seconds. The current remained at this level for the specified amount of time in the active condition (e.g., 20-minutes) but was ramped down over the next 30 seconds for those in the sham condition. This ramp up/down process was repeated in the final minute (e.g., 20th minute) in the sham session to provide both primacy and recency effects. After each active or sham session, participants were asked whether they received 'real’ or sham stimulation. One study also asked a study team member if they believed the participant received real or sham stimulation at two primary outcome endpoints.
Results:We used Fisher’s Exact tests to evaluate the efficacy of our blinding and double-blinding procedures. In stimulation naive participants receiving their first session, there were no differences in accuracy, suggesting adequate blinding. We also examined participant blinding across all sessions to determine whether repeated HD-tDCS exposure might impact blinding. Across all sessions, participants in the sham condition were more likely to endorse being in the 'real’ (active) condition, again suggesting adequate blinding. There were no significant group differences for active versus sham in the frequency of the study team correctly stating the participant’s condition, suggesting sufficient double-blinding. No significant differences were found in study team blinding when data from the 2mA versus 4mA to 6mA were analyzed separately.
Conclusions:These results suggest that the HD-tDCS sham method is an effective blind and double-blind for HD-tDCS in clinical trials, even at total amplitudes as high as 6mA.
40 Positive and Negative Emotional Outcomes Following Alzheimer’s Disease Biomarker Disclosure in Cognitively Symptomatic Older Adults
- Mary R. Lesniak, Marie Milliken, Sara Feldman, Scott J. Roberts, Benjamin M. Hampstead, Annalise M. Rahman-Filipiak
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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. 248-249
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Objective:
There are many potential benefits of early identification of those with Alzheimer’s disease (AD), including more opportunity for early intervention to slow AD progression (e.g., treatment, lifestyle changes, etc.) and to plan for the future. Positron emission tomography (PET) scans for abnormal amyloid and tau are commonly conducted in research settings. Despite strong interest in learning AD biomarker results, participants rarely receive their research data, in part due to concern about the possibility of undue distress based on results. We aimed to explore both positive and negative emotional reactions following PET biomarker disclosure as a function of result received.
Participants and Methods:Forty-three older adults (age = 72.0±6.21 years, education = 16.5±2.62 years, 49% Female, 88% White Non-Hispanic) completed PET amyloid and tau testing and disclosure. Sixty-three percent were diagnosed with mild cognitive impairment (MCI) while the remainder of participants were diagnosed with Dementia Alzheimer’s type (DAT). Participants completed pre-disclosure biomarker education and a decisional capacity assessment followed by baseline measures. Participants then completed a disclosure session where they received personal PET amyloid and tau results on an elevated vs. not elevated scale for each ligand. Results were discussed in relation to presence/absence of Alzheimer’s disease, how the result relates to their cognitive difficulties, and risk of developing Dementia-Alzheimer’s Type. At baseline (pre-disclosure), immediately post-disclosure, and 1-week post-disclosure, participants completed the Beck Anxiety Inventory (BAI), The Geriatric Depression Scale - 15 Item (GDS-15), Impact of Neuroimaging in AD (INI-AD) Scale, and the Positive and Negative Affective Scale - Short Form (PANAS-SF). All questionnaires were modified to apply to Alzheimer’s disease and related experiences.
Results:Of the 43 participants who participated in disclosure, 74% received biomarker positive results (either A+T- or A+T+); all others were biomarker negative. We conducted a series of mixed analysis of variance (ANOVA) tests to determine the effect of disclosure and biomarker status for each of the outcomes of interest. Neither the effect of time nor the time by biomarker status interaction was significant for any of the outcomes (all p>.05). The main effect of biomarker status was significant for BAI (F(1)=5.12, p=.031, n,p2=.146) and INI-AD Distress (F(1)=12.70, p=.001, np2=.241) and Positive (F(1)=34.57, p<.001, np2=.464) subscale scores with A+T-/A+T+ participants reporting higher negative affect than those who were A-/T-; however, even among biomarker positive individuals, scores did not exceed clinical thresholds. GDS-15, PANAS-Negative and Positive Subscale scores did not differ significantly by biomarker status (all p>.05) and no significant adverse events occurred following disclosure. Additionally, no participants cited regret about receiving their results.
Conclusions:While disclosure of biomarker positivity may result in mild increases in acute anxiety or distress, or fewer positive emotions, it does not result in clinically significant emotional reactions and was not associated with regret. Overall, findings are consistent with literature indicating safety of biomarker disclosure procedures for symptomatic individuals. Future research should follow participants over longer periods to evaluate the impacts of biomarker disclosure.
97 Evaluation of Video and Telephone-Based Administration of the Uniform Data Set Version 3 (UDS v3.0) Teleneuropsychological Measures
- Theresa F. Gierzynski, Allyson Gregoire, Jonathan M. Reader, Rebecca Pantis, Stephen Campbell, Arijit Bhaumik, Annalise Rahman-Filipiak, Judith Heidebrink, Bruno Giordani, Henry Paulson, 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. 499-500
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Objective:
Telecommunication-assisted neuropsychological assessment (teleNP) has become more widespread, particularly in response to the COVID-19 pandemic. However, comparatively few studies have evaluated in-home teleNP testing and none, to our knowledge, have evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study compares in-home teleNP administration of the UDS v3.0, acquired while in-person activities were suspended due to COVID-19, with a prior in-person UDS v3.0 evaluation.
Participants and Methods:210 participants from the Michigan Alzheimer’s Disease Research Center’s longitudinal study of memory and aging completed both an in-person UDS v3.0 and a subsequent teleNP UDS v3.0 evaluation. The teleNP UDS v3.0 was administered either via video conference (n = 131), telephone (n = 75), or hybrid format (n = 4) with approximately 16 months between evaluations (mean = 484.7 days; SD = 122.4 days; range = 320-986 days). The following clinical phenotypes were represented at the initial assessment period (i.e., the most recent in-person UDS v3.0 evaluation prior to the teleNP UDS v3.0): cognitively healthy (n = 138), mild cognitive impairment (MCI; n = 60), dementia (n = 11), and impaired not MCI (n = 1). Tests included both the in-person and teleNP UDS v3.0 measures, as well as the Hopkins Verbal Learning Test-Revised (HVLT-R) and Letter “C” Fluency.
Results:We calculated intraclass correlation coefficients (ICC) with raw scores from each time point for the entire sample. Sub-analyses were conducted for each phenotype among participants with an unchanged consensus research diagnosis: cognitively healthy (n = 122), MCI (n = 47), or cognitively impaired (i.e., MCI, dementia, and impaired not MCI) (n = 66). Test-retest reliability across modalities and clinical phenotypes was, in general, moderate. The poorest agreement was associated with the Trail Making Test (TMT) - A (ICC = 0.00; r = 0.027), TMT - B (ICC = 0.26; r = 0.44), and Number Span Backward (ICC = 0.49). The HVLT-R demonstrated moderate reliability overall (ICC = 0.51-0.68) but had notably weak reliability for cognitively healthy participants (ICC = 0.12-0.36). The most favorable reliability was observed in Craft Story 21 Recall - Delayed (ICC = 0.77), Letter Fluency (C, F, and L) (ICC = 0.74), Multilingual Naming Test (MINT) (ICC = 0.75), and Benson Complex Figure – Delayed (ICC = 0.79).
Conclusions:Even after accounting for the inherent limitations of this study (e.g., significant lapse of time between testing intervals), our findings suggest that the UDS v3.0 teleNP battery shows only modest relationships with its in-person counterpart. Particular caution should be used when interpreting measures showing questionable reliability, though we encourage further investigation of remote vs. in-person testing under more controlled conditions.
66 Tolerability of HD-tDCS at Total Amplitudes of 2mA to 10mA in Older Adults
- Ashley Harrie, Carine El Jamal, Michael Padgett, Annalise Rahman-Filipiak, 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. 473-474
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Objective:
High-definition transcranial direct current stimulation (HD-tDCS) is a non-invasive form of brain stimulation used to modulate neuronal activity in a brain region of interest. Growing research has shown that HD-tDCS is a promising treatment for cognitive decline in neurodegenerative disease. Most HD-tDCS studies have used amplitudes of 2mA or less, with little investigation into tolerability at greater intensities since anecdotal lore generally suggests them to be poorly tolerated. Therefore, we examined the tolerability of HD-tDCS and common side effect profile in older adults who received total amplitudes of 3mA to 10mA (delivered using multiple electrodes delivering 2-4mA). We developed a series of methods (e.g., participant instructions, task engagement, techniques to lower impedance) and hypothesized they would equate the experience between active and sham HD-tDCS. We also compared symptom endorsement between those receiving active stimulation at 3mA+ total versus those receiving 2mA or lower; again, hypothesizing no difference in reported symptoms.
Participants and Methods:295 older adults (Mage = 71.12±9.42) (Normal Cognition = 75, Amnestic MCI [aMCI] = 172, Dementia of the Alzheimer's Type [DAT] = 27, Other = 21) were enrolled across six HD-tDCS studies. All participants received one to thirty 20- to 30-minute sessions of active or sham stimulation at total amplitudes between 2mA and 10mA. All participants completed a standardized side effect questionnaire after each session asking whether they experienced burning, tingling, itching, scalp pain, trouble concentrating, sleepiness, headache, mood changes, neck pain, skin redness, or any other symptoms. When symptoms were endorsed, participants rated the severity of the symptom (mild, moderate, severe).
Results:We used Fisher's Exact tests to compare the frequency and severity of side effects in active (3mA or higher) vs. sham stimulation. Those receiving sham were significantly more likely to report tingling than those receiving active HD-tDCS. Conversely, those receiving active stimulation more frequently endorsed mood changes and skin redness relative to the sham group, though moderate-severe ratings were endorsed in only 2.9% and 0.4% of the sessions, respectively. Relative to those receiving 2mA, participants receiving higher intensities of active stimulation experienced skin redness more frequently, whereas the 2mA reported higher frequencies of itching and scalp pain. A burning sensation was endorsed at equal rates between these groups; however, the higher intensity active group reported it as moderate or severe more frequently than the 2mA active group. Despite these minor differences, most side effects following 3mA+ were reported at low frequencies and were typically mild when endorsed.
Conclusions:Our findings demonstrate that HD-tDCS is well-tolerated for total amplitudes up to 10mA in older adults with little tangible difference in the reported experience relative to sham. Findings support the use of higher HD-tDCS amplitudes, at least when key methodological procedures are followed.
Evaluation of the Uniform Data Set version 3 teleneuropsychological measures
- Theresa F. Gierzynski, Allyson Gregoire, Jonathan M. Reader, Rebecca Pantis, Stephen Campbell, Arijit Bhaumik, Annalise Rahman-Filipiak, Judith Heidebrink, Bruno Giordani, Henry Paulson, Benjamin M. Hampstead
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 2 / February 2024
- Published online by Cambridge University Press:
- 27 June 2023, pp. 183-193
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Objective:
Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation.
Method:One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference (n = 122) or telephone (n = 59).
Results:We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01–0.79) but were generally indicative of “moderate” (i.e., ICCs ranging from 0.5–0.75) to “good” (i.e., ICCs ranging from 0.75–0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35–0.87) were found between similarly timed in-person UDS v3.0 evaluations.
Conclusions:Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.