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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.
19 Accuracy of Self- and Informant-Reported Domain-Specific Cognitive Ratings
- Haley S Kohl, Allyson Gregoire, Jonathan Reader, Arijit Bhaumik, Bruno Giordani, Henry Paulson, Benjamin Hampstead, Annalise 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. 702-703
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Objective:
Diagnostic criteria for mild cognitive impairment (MCI) include a report of cognitive decline from the patient or a close informant. It is therefore important to understand the relationship between self- and informant-rated cognition and actual patient performance. Furthermore, it is unknown whether the nature of the relationship between the patient and their informant impacts accuracy of subjective reports. This study aimed to determine the association between informant report, self-report and objective cognitive performance based on relationship factors. We predicted that informant report would be more closely associated with objective performance than self-report after controlling for demographics and mood (Geriatric Depression Scale [mean= 1.4, SD=2]), especially among those who live with the participant and those who are spouses/partners.
Participants and Methods:Participants (n = 338; age= 73.5 ±6.7) of varying diagnoses and their respective informants were drawn from the longitudinal cohort of the Michigan Alzheimer’s Disease Research Center (MADRC). The majority of informants were spouses/significant others (55.6%), followed by 23.7% being other family members and 20.7% were non- family members; 58.9% of informants live with the participant. Both respondents completed the Cognitive Change Index (CCI) to rate the patient’s cognitive status (higher scores indicating worsening cognition) across three domains: memory (12 questions), language (1 question), and attention/executive functioning (7 questions). These domains were matched to objective cognitive performance measured using the MADRC neuropsychological battery. Executive functioning and attention were assessed using Number Span Test Forward and Backward (NSF, NSB) and Trail Making Test Part B and Trail- Making Test Part A and B ratio (TMTB, TMTB: A); memory was measured using Craft Story 21 (Immediate and Delayed), Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, Delayed Recall, and Benson Complex Figure (BCF) Delayed Recall; and Language was measured by the Controlled Oral Word Association Test (COWAT) and Animal fluency.
Results:Linear regression adjusted for sex, race, and mood indicated that both patient and informant CCI ratings were significantly (p<.05) associated with objective cognitive performance. For every one unit increase on executive CCI items, there was a significant decline in executive functioning (NSF patient and informant ß= -0.09, NSB: [ßP= -.14; ßp-0.13]) and TMTB [ßP= 3.85; ß= 3.10 [% change]). Memory performance also declined per unit increase on CCI memory items: (Craft Story 21 Immediate [ßP=-0.32; ß= -0.37] and Delayed [ßP=-.40; ßp -.47], HVLT-R Total Recall [ßP= -.31; ßI=-.37] and Delayed Recall [ßP= -.16; ß=-.20], and BCF Delayed Recall [ßP= -.18; ß= -.23]. Similarly, one unit increase on the single CCI language item was associated with a decline in COWAT (ßP= -2.27; ß= -4.61) and Animal fluency (ßP= -1.88; ß= -3.03). Effect modification by participant-informant relationship type or participant-informant cohabitation was not significant.
Conclusions:Patient and informant ratings are associated with objective measures of cognition regardless of the relationship between informant and patient or if they live together. This study was limited by a well-educated sample (mean= 16.1 years of education, SD= 2.4 years) with relatively limited diversity among participant-informant relationships. Future studies should replicate analyses across a larger and more diverse sample.
1 Basal Forebrain Free Water Fraction is Associated with Cortical Cholinergic Levels in Idiopathic Parkinson’s Disease
- Samuel J Crowley, Prabesh Kanel, Stiven Roytman, Nicolaas I Bohnen, 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. 108-109
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Cognitive dysfunction is a common non-motor symptom of Parkinson’s disease (PD). Cognitive decline in PD is likely associated with dysfunction in the cholinergic system, which is affected by synuclein pathology early in the disease course. Recent studies have shown an association between reduced integrity of the basal forebrain (BF), which provides cholinergic innervation to most of cortex, and diminished cognitive functioning in PD. Specifically, those with PD and reduced cholinergic innervation also have higher rates of cognitive impairment. However, no study has directly investigated the relationship between basal forebrain integrity and cortical cholinergic levels. In the present study, we examined this relationship through measures of basal forebrain microstructural integrity and cholinergic nerve terminal density in cortical and subcortical gray matter.
Participants and Methods:Participants included 92 non-demented individuals with idiopathic PD (M:F=64:28; Age=67.0±7.1 yrs) who underwent structural MRI, diffusion MRI, and [18F] fluoroethoxybenzovesamicol (FEOBV) cholinergic PET imaging. We used a basal forebrain and region of interest defined by AssemblyNet, which uses ensembles of pretrained convolutional neural networks to create a full brain segmentation. Bilateral putamen from this atlas was also included as a control region. We measured microstructural integrity using free water fraction (FWF), a diffusion MRI-derived metric of extracellular water that associates with cellular density and neuroinflammation. For PET data, we computed the distribution volume ratio (DVR) by regions as defined by FreeSurfer. A factor analysis of DVR in all 88 FreeSurfer ROIs resulted in seven clusters of ROIs covering 1) widespread bilateral cortical regions (PC1); 2) subcortical and limbic regions (PC2); 3) bilateral cingulate regions (PC3); 4) left frontal regions (PC4); 5) right frontal and temporal regions (PC5); 6) cerebellum (PC6); and 7) bilateral entorhinal cortex and left temporal cortex (PC7). We performed seven separate regression analyses per ROI (controlling for age and disease duration) to evaluate the association between BF FWF and cholinergic levels in these regions. To determine if these ROIs showed unique associations with BF FWF, we then entered ROIs with a significant association with BF FWF as independent variables in a stepwise regression with forward selection with BF FWF as the dependent variable.
Results:BF FWF was significantly and negatively associated with cholinergic levels in PC1 (AR2=.042, ß=-0.208, p=.04), PC3 (AR2=.044, ß=-0.206, p=.03), PC4 (AR2=.056, ß=-0.239, p=.02), and PC7 (ß=-0.215, p=.04). BF FWF trended towards a negative association with cholinergic levels in PC5 (AR2=.045, ß=-0.168, p=.09) and PC6 (ß=-0.188, p=.09). Putamen FWF did not significantly associate with any of the ROIs. In the follow-up stepwise regression, only PC4 contributed significantly to the overall model (AR2=.061, ß=-0.261, p=.02).
Conclusions:Basal forebrain FWF was inversely related to cholinergic levels in regions that are directly innervated by the basal forebrain (e.g., cingulate cortex, left frontal cortex, and bilateral entorhinal cortex). Future research should directly investigate the relationship between basal forebrain integrity, cortical cholinergic levels, and cognition. Separating the basal forebrain into specific nuclei would also be beneficial, as different nuclei may have differing associations with specific hemispheric cholinergic pathways and cognition.
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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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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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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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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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.
57 Sensitivity of functional Near-Infrared Spectroscopy in Individuals with Posterior Cortical Atrophy
- Victor Di Rita, Anthony Moceri, Megan Schumer, Michael Padgett, Alexandru Iordan, Benjamin 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, p. 466
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Functional near infrared spectroscopy (fNIRS) is a form of non-invasive neuroimaging that uses light to measure changes in oxygenated and deoxygenated hemoglobin (Yucel et. al., 2021). Relative to fMRI, fNIRS is significantly cheaper and less susceptible to motion artifacts thereby enabling researchers to acquire data in more ecologically valid environments and has a higher temporal resolution that makes it well-suited for connectivity analyses (Tak and Ye, 2014). fNIRS is, however, uniquely limited by cortical anatomy. With a typical probe array having a penetrance depth of up to 3cm, the benefits of fNIRS may be limited by the neocortical atrophy that is characteristic in those with neurodegeneration. We present preliminary findings comparing fNIRS probe sensitivity in older adults diagnosed with posterior cortical atrophy (PCA) relative to cognitively intact older adults using Monte Carlo (MC) simulations. MC simulations offer probabilistic models that simulate photon movement through tissues of interest. We were particularly interested in fNIRS' sensitivity in the occipitoparietal cortices since these are regions characteristically affected in PCA.
Participants and Methods:We acquired high resolution structural (T1) MRI on 3 cognitively intact older adults and 3 individuals who received a clinical diagnosis of PCA according to Crutch et al. (2017) criteria. Individual T1 scans were preprocessed and transformed into a twodimensional (2D) surface using FreeSurfer. This continuous 2D surface was then segmented into its main tissue priors, as well as its pial surfaces. Segmented MRIs were then imported into AtlasViewer software and registered to our full head fNIRS probe array via an affine transformation. We embedded the GPU-accelerated Monte Carlo Extreme 3D light transport simulator software (Fang and Boas, 2009) into AtlasViewer which enabled us to launch 10 million photons from each optode, compared to the 1 million that AtlasViewer is set to by default, thereby providing more accurate results (Aasted et. al., 2015). We then assessed the sensitivity profile (log units), a mathematical estimate of optical density, of the inferior and superior occipital gyri, middle occipital gyrus, the superior and inferior parietal lobules, and left and right precunei.
Results:Among the regions interrogated, five channels on our fNIRS probe were markedly different between the controls and those with PCA. Specifically, sensitivity values for channels covering the right inferior (hedges g = 8.04) and left superior occipital gyrus (hedges g = 2.46), the right inferior parietal lobule (hedges g = 8.89), and the right (hedges g = 9.43) and left (hedges g = 14.83) precunei were all markedly lower in those with PCA.
Conclusions:We provided preliminary evidence that the sensitivity of fNIRS appears to be markedly reduced in those with PCA. This is especially relevant for researchers using fNIRS in populations with neurodegeneration. Future work will evaluate these findings in a larger sample as well as in other neurologic conditions with the goal of helping researchers appropriately power their studies and interpret their results.
77 Differentiating Amnestic Versus Non-Amnestic Mild Cognitive Impairment Using the NIH Toolbox Cognition Battery
- Cameron K Perrin, Amanda Cook Maher, Allyson Gregoire, Jonathan Reader, Arijit Bhaumik, Benjamin M Hampstead, Bruno Giordani
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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. 380-381
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In research, and particularly clinical trials, it is important to identify persons at high risk for developing Alzheimer’s Disease (AD), such as those with Mild Cognitive Impairment (MCI). However, not all persons with this diagnosis have a high risk of AD as MCI can be broken down further into amnestic MCI (aMCI), who have a high risk specifically for AD, and non-amnestic MCI (naMCI), who are predominantly at risk for other dementias. People with aMCI largely differ from healthy controls and naMCI on memory tasks as it is the hallmark criteria for an amnestic diagnosis. Given the growing use of the NIH Toolbox Cognition battery in research trials, this project investigated which Toolbox Cognition measures best differentiated aMCI from naMCI and in comparison to persons with normal cognition.
Participants and Methods:A retrospective data analysis was conducted investigating performance on NIH Toolbox Cognition tasks among 199 participants enrolled in the Michigan Alzheimer’s Disease Research Center. All participants were over age 50 (51-89 years, M=70.64) and had a diagnosis of aMCI (N=74), naMCI (N=24), or Normal Cognition (N=101). Potential demographic differences were investigated using chi-square and ANOVAs. Repeated measure general linear model was used to look at potential group differences in Toolbox Cognition performance, covarying for age which was statistically different in aMCI versus Normal participants. Linear regression was used to determine which cognitive abilities, as measured by the Uniform Data Set-3 (UDS3), might contribute to Toolbox differences noted in naMCI versus aMCI groups.
Results:As expected, aMCI had lower Toolbox memory scores compared to naMCI (p=0.007) and Normals (p<0.001). Interestingly, naMCI had lower Oral Reading scores than both aMCI (p=0.008) and Normals (p<0.001). There were no other Toolbox performance differences between the MCI groups. 19.4% of the variance in Oral Reading scores was explained by performance on the following UDS3 measures: Benson delayed recall (inverse relationship) and backward digit span and phonemic fluency (positive relationship).
Conclusions:In this study, Toolbox Picture Sequence Memory and Oral Reading scores differentiated aMCI and naMCI groups. While the difference in memory was expected, it was surprising that the naMCI group performed worse than the aMCI and normal groups on the Toolbox Oral Reading task, a task presumed to reflect Crystalized abilities resistive to cognitive decline. Results suggest that Oral Reading is primarily positively associated with working memory and executive tasks from the UDS3, but negatively associated with visual memory. It is possible that the Oral Reading subtest is sensitive to domains of deficit aside from memory that can best distinguish aMCI from naMCI. A better understanding of the underlying features in the Oral Reading task will assist in better characterizing deficit patterns seen in naMCI, making selection of aMCI participants more effective in clinical trials.
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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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.
The association between cannabis use and subjective memory complaints in older adults in the United States
- Kyler Mulhauser, Benjamin M. Hampstead, Lara N. Coughlin, Mark A. Ilgen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 9 / November 2023
- Published online by Cambridge University Press:
- 20 February 2023, pp. 870-877
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Objective:
The U.S. population is aging and increasing numbers of older adults are using cannabis. Cognitive decline is common in older age and subjective memory complaints (SMC) have been associated with increased risk for dementia. While residual cognitive effects of cannabis use at younger ages are well understood, the links between cannabis use and cognition in older adults is less clear. The present study represents the first population-level analysis of cannabis use and SMC in older adults in the U.S.
Method:We used the National Survey of Drug Use and Health (NSDUH) dataset to evaluate SMC in respondents over age 50 (N = 26,399) according to past-year cannabis use.
Results:Results revealed that 13.2% (95%CI: 11.5%−15.0%) of those who reported cannabis use also reported SMC, compared to 6.4% (95%CI: 6.1%–6.8%) among individuals with no cannabis use. Logistic regression revealed a two-fold increase (OR = 2.21, 95%CI: 1.88–2.60) of reporting SMC in respondents who had used cannabis in the past year, which was attenuated (OR = 1.38, 95%CI: 1.10–1.72) when controlling for additional factors. Other covariates, including physical health conditions, misuse of other substances, and mental illness also significantly contributed to SMC outcomes.
Conclusions:Cannabis use represents a modifiable lifestyle factor that has potential for both risk and protective properties that may impact the trajectory of cognitive decline in older age. These hypothesis generating results are important for characterizing and contextualizing population-level trends related to cannabis use and SMC in older adults.
3010 Effects of non-invasive brain stimulation on speech fluency and brain activity in adults who stutter: a randomized controlled clinical trial
- Emily O’Dell Garnett, Soo-Eun Changv, Benjamin Hampstead, Ho Ming Chow
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 42-43
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OBJECTIVES/SPECIFIC AIMS: The goal of this study is to measure speech fluency and brain activity before and after 5 days of behavioral speech fluency training alone (sham group) or speech training plus stimulation (active group). A 1-month follow up will also be completed. The first primary outcome measure is changes in brain activation in speech motor control/timing network. The second primary outcome measure is changes in percentage of stuttered syllables during speech sample (speech fluency). The secondary outcome measure is changes from baseline on the Overall Assessment of Speakers Experience of Stuttering (OASES), a detailed subject rating of how stuttering affects their lives. METHODS/STUDY POPULATION: This study is a between subjects, counterbalanced, sham-controlled, double-blind design. Participants will be 40 adults who stutter who will be randomized (using minimization) into either the active or sham stimulation group, with all other study procedures being the same in both groups. Participants will completed 2 days of baseline testing, 5 consecutive days of brain stimulation during speech training, 2 days of post-testing, and a 1-month follow up. All outcome measures will be completed immediately before and after the 5 days of brain stimulation, as well as at follow-up. as of submission, 10 subjects have completed the study. Data collection is ongoing. RESULTS/ANTICIPATED RESULTS: Expected results. Questions this study aims to answer: 1) Does a more intensive training period lead to decreased stuttering? We expect that both groups will show improvements in speech fluency immediately after training. We expect that those in the active group will continue to exhibit improved speech fluency at 1 month follow up. 2) Does a more intensive training period lead to changes in brain activity? We expect that both groups will exhibit increased activity in auditory/motor regions immediately after training. We expect that the active group will continue to exhibit an increase in activity in these regions at 1 month follow up. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first RCT study involving brain stimulation in adults who stutter. We expect to provide preliminary evidence for the effectiveness of tDCS as an augmentative agent for increased speech fluency in adults who stutter during a brief, intensive training paradigm. We also expect to be able to provide information on the effects of tDCS on brain activity in speech and auditory-motor regions of the brain. The findings will add to the growing body of literature suggesting that developmental stuttering is a neurodevelopmental disorder with roots in timing and rhythmic aspects of speech motor control and auditory-motor integration.
Cognitive Rehabilitation of Memory for Mild Cognitive Impairment: A Methodological Review and Model for Future Research
- Benjamin M. Hampstead, M. Meredith Gillis, Anthony Y. Stringer
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- Journal:
- Journal of the International Neuropsychological Society / Volume 20 / Issue 2 / February 2014
- Published online by Cambridge University Press:
- 13 December 2013, pp. 135-151
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Several recent reviews have suggested that cognitive rehabilitation may hold promise in the treatment of memory deficits experienced by patients with mild cognitive impairment. In contrast to the previous reviews that mainly focused on outcome, the current review examines key methodological challenges that are critical for designing and interpreting research studies and translating results into clinical practice. Using methodological details from 36 studies, we first examine diagnostic variability and how the use of cutoffs may bias samples toward more severely impaired patients. Second, the strengths and limitations of several common rehabilitative techniques are discussed. Half of the reviewed studies used a multi-technique approach that precludes the causal attribution between any specific technique and subsequent improvement. Third, there is a clear need to examine the dose-response relationship since this information was strikingly absent from most studies. Fourth, outcome measures varied widely and frequently depended on neuropsychological tests with little theoretical justification or ecological relevance. Fifth, we discuss how the variability in each of these other four areas complicates efforts to examine training generalization. Overall, future studies should place greater emphasis on ecologically relevant treatment approaches and outcome measures and we propose a hierarchical model that may aid in this pursuit. (JINS, 2014, 19, 1–17)
Explicit memory training leads to improved memory for face–name pairs in patients with mild cognitive impairment: Results of a pilot investigation
- BENJAMIN M. HAMPSTEAD, K. SATHIAN, ANNA BACON MOORE, CARRIE NALISNICK, ANTHONY Y. STRINGER
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- Journal:
- Journal of the International Neuropsychological Society / Volume 14 / Issue 5 / September 2008
- Published online by Cambridge University Press:
- 03 September 2008, pp. 883-889
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Relatively few studies have examined the use of cognitive rehabilitation in patients with mild cognitive impairment (MCI), largely due to the assumption that training will not improve functioning in patients with progressive conditions. Face-name association, an ecologically valid task, is both dependent on the explicit memory system and difficult for MCI patients. During three hour-long sessions, eight patients diagnosed with MCI were trained in the use of explicit memory strategies with 45 face-name pairs. For each pair, they were taught to visually identify a facial feature, link a phonological cue to that feature, and recall the associated name. There was significant improvement in recognition accuracy, along with faster reaction times, for trained face-name pairs. Improved accuracy persisted when tested one month after training. Significant, but less, improvement was also found on untrained stimuli, raising the possibility of generalization of training strategies. Preliminary results suggest strategy-based cognitive rehabilitation may be beneficial in patients with MCI, though these results must be replicated with a control group to rule out practice effects. (JINS, 2008, 14, 883–889.)