Browsing by Author "Hammers, Dustin"
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Item Developments in understanding early onset Alzheimer’s disease(Wiley, 2023) Griffin, Percy; Apostolova, Liana; Dickerson, Bradford C.; Rabinovici, Gil; Salloway, Stephen; Raghuram, Srilath; Brandt, Katie; Hall, Stephen; Masdeu, Joseph; Carrillo, Maria C.; Hammers, Dustin; Neurology, School of MedicineOn September 25 and 26, 2021, the Alzheimer's Association hosted the first meeting focused on people with early-onset Alzheimer's disease (EOAD)-sometimes referred to as younger onset Alzheimer's disease (AD). Though a diagnosis of AD can be devastating at any age, those with a younger onset-defined as symptoms developing prior to 65 years of age-face unique challenges. EOAD occurs when people are in the prime of their lives, often with multiple responsibilities including careers, community activities, and raising children and caring for older family members. These challenges warrant special consideration and study, yet people with EOAD are often excluded from AD research because of their atypical age of onset. To help fill this gap, we designed and launched the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) to enroll and follow 500 people with EOAD from > 15 sites in the United States, which the National Institute on Aging funded in 2018. The September 2021 meeting was designed to inform people with EOAD and their family members and caregivers about the latest research on the biology of EOAD, treatments in the pipeline, practical considerations about legal and financial arrangements for families, and the support networks available to them. More than 217 registrants attended.Item Exploring Factors Contributing to Caregiver Burden in Family Caregivers of Congolese Adults with Suspected Dementia(Wiley, 2023) Ikanga, Jean; Reyes, Anny; Zhao, Liping; Hill-Jarrett, Tanisha G.; Hammers, Dustin; Epenge, Emmanuel; Esambo, Herve; Kavugho, Immaculée; Esselakoy, Christian; Gikelekele, Guy; Tshengele, Nathan; Alonso, Alvaro; Robinson-Lane, Sheria G.; Neurology, School of MedicineIntroduction: Predicting caregiver burden in individuals with suspected dementia - is critical due to the debilitating nature of these disorders and need for caregiver support. While some examination of the factors affecting burden has been undertaken in Sub-Saharan Africa, each country presents with its own unique challenges and obstacles. This pilot study investigates predictors of caregiver burden in family caregivers of individuals with suspected dementia living in the Democratic Republic of the Congo (DRC). Methods: Linear and multiple regression analyses were conducted to explore factors associated with caregiver burden in 30 patient-caregiver dyads with the Zarit Burden Interview (ZBI) for caregiver burden evaluation. Cognitive impairments of patients were assessed using the Community Screening Instrument for Dementia, Alzheimer's Questionnaire (AQ), the African Neuropsychology Battery, and the Neuropsychiatric Symptoms Inventory (NPI). Results: Average caregiver burden on the ZBI was 36.1 (SD = 14.6; range = 12-58). Greater impairments in patient cognition (orientation, visuospatial, memory, executive functioning), fragility, and neuropsychiatric symptoms (delirium, agitation, depression) were predictive of caregiver burden. After controlling for AQ scores and caregiver gender, greater symptoms of depression, and worse performances on verbal memory and problem solving were associated with greater caregiver burden. Conclusion: Worsening patient fragility, cognition, functioning, and neuropsychiatric symptoms influenced caregiver burden in caregivers of individuals with suspected cognitive impairment in the DRC. These findings are consistent with the prior literature. Future studies may wish to explore supportive factors and caregiver specific characteristics that buffer against perceived burden.Item Feasibility and Acceptability of Using Plasma Biomarkers for Diagnosing Alzheimer’s Disease in Primary Care(Oxford University Press, 2023-12-21) Fowler, Nicole; Swartzell, Kristen; Hammers, Dustin; Brosch, Jared; Murray, James; Willis, Deanna; Medicine, School of MedicineBlood-based biomarkers (Aβ, P-tau, neurofilament light) are clinically available to aid in the diagnosis of Alzheimer’s disease and related dementias (ADRD). However, no research has examined the use of blood biomarkers to aid in the diagnosis of ADRD in primary care (PC). Our study will test feasibility and acceptability of implementing blood-based biomarkers for ADRD in PC. Participants include: all PC patients ≥65 years presenting to one of six PC clinics between 6/1/22 and 5/31/23 who score cognitively impaired on the Linus Health Digital Clock and Recall (DCR™), and PC providers (PCPs) of these patients. Patients will view a decision guide about biomarkers and complete the Concerns about Alzheimer’s Disease Dementia Scale, and the Future Time Perspective Scale and the Impact of Events Scale. These measures and the PHQ-9 and GAD-7 will be repeated within 2 weeks of results disclosure. PCPs will receive training on biomarker disclosure techniques and best practices. To date 9 PCPs have consented to provide the biomarker results disclosure and 11 have declined. Following completion of PCP consent (n=100), a total of 200 patients who failed the DCR are eligible to be approached for consent. By November 2023, we anticipate that 150 patients will have completed biomarker testing, and we will have examined the biomarker results in the context of patient neuropsychological and clinical data, comorbidities, and sociodemographic information. This study will provide information regarding feasibility and utility of ADRD biomarkers in PC and a preliminary analysis of biomarker results compared with the patients’ clinical profiles.Item Feasibility of Recruiting People With Mild Cognitive Impairment in the Context of Heart Failure(Oxford University Press, 2024-12-31) Jung, Miyeon; Pressler, Susan; Hammers, Dustin; Apostolova, Liana; School of NursingRecruiting people with mild cognitive impairment (MCI) with another chronic condition such as heart failure (HF) can be arduous. Our investigative group will discuss the challenges encountered while recruiting older adults with both MCI and HF using data from a pilot study testing the efficacy of cognitive interventions to improve cognitive function and the strategies to overcome them. Initially, eligibility criteria included age ≥65 years, HF confirmed by echocardiography, and MCI defined using a 2-step process: (1) Montreal Cognitive Assessment (MoCA) ≤23; and (2) diagnostic consensus of MCI based on the presence of cognitive impairment in the absence of functional decline. Enrollment began on 4/3/2023 by screening Cardiology and Neurology clinics patients. Only 12 participants were enrolled over the next 7 months (rate=1.5 participants/month) due to high screen failure rates (59%) owing to MoCA performances above the eligibility threshold and low recruitment rate (5%). To meet recruitment goals (8 participants/month), eligibility criteria were modified by lowering the age cutoff from 65 to 55 years and removing the MoCA screen and the MCI requirements, while adding the requirement of subjective cognitive concern allowing both those with normal cognition and MCI but not dementia. Phone recruitment was added by screening electronic health records of people who diagnosed with HF. 7 months after implementing the modifications, additional 58 participants were consented exceeding our recruitment goals (69% of those consented=MCI, 26%=normal cognition, 5%=dementia/excluded from the study). In conclusion, feasibility of our original strategies recruiting older adults with both MCI and HF was not supported.Item Implementation of a Digital Cognitive Screening Program for Dementia in Primary Care(Oxford University Press, 2023-12-21) Fowler, Nicole; Mullavey, Judy; Swartzell, Kristen; Hammers, Dustin; Brosch, Jared; Murray, James; Willis, Deanna; Medicine, School of MedicineEarly identification of Alzheimer’s disease and related dementias (ADRD) has become paramount given the emergence of disease modifying therapies. Integration of rapid, scalable tools to identify early cognitive impairment in primary care is essential because most at-risk individuals have limited access to specialty care. Yet, competing demands on primary care practices can make integration challenging. This demonstration project is being conducted to understand the feasibility, acceptability, and implementation of digital cognitive screening in primary care. Patients ≥65 years presenting to one of six primary care sites between 06/01/2022 and 06/30/2023 are asked to complete the Linus Health Digital Clock and Recall (DCR™) cognitive screening. Data regarding number of screening attempts that were refused, incomplete, or completed was collected. Results of the first completed screening-results were analyzed using descriptive statistics. As of 2/15/23, there are 3,920 screening attempts. DCR™ screenings were completed 40.8% of the time, refused 57.4%, and attempted but incomplete 1.8%. Thirteen-percent of attempts were positive for cognitive impairment, 37% were borderline, 44% were unimpaired, and 6% were unanalyzable. Average patient age is 73.2±6.0 years, 58% female, and 6% report less than high school education. Patients with positive screenings are older, slightly more female, and reported less education. Cognitive screening via DCR™ is ongoing and has been completed in nearly half of those approached, with half scoring cognitively impaired or borderline. This approach appears to have utility in early detection of cognitive impairment in primary care. By November 2023 we will have follow-up data for patients who screened positive.Item Predicting daily functioning with the modified Telephone Interview for Cognitive Status(Springer Nature, 2022) Dixon, Ava; Porter, Sariah; Suhrie, Kayla; Hammers, Dustin; Duff, Kevin; Neurology, School of MedicineBackground: The modified Telephone Interview for Cognitive Status (mTICS) is a frequently used telephone-based cognitive screening measure that can distinguish between normal aging, mild cognitive impairment (MCI), and dementia. Although it has been used to predict current and future cognitive function in older adults, no studies have examined if the mTICS can predict daily functioning. Aims: The current study sought to examine the relationship between the mTICS and a performance-based measure of daily functioning. Methods: The mTICS and demographic information (age, sex, education) were collected during a telephone screening visit for 149 older adults (65-91 years in age) with amnestic MCI. Three subscales of the Independent Living Scales (ILS; Managing Money, Managing Home and Transportation, Health and Safety) were collected during a baseline visit and during a 16 month follow-up visit in a subsample of 93 individuals. Results: Using simple hierarchical regression, baseline mTICS total score combined with demographic variables significantly predicted 19-22% of baseline ILS subscale scores. Similarly, in a subsample of 93 participants with 16 month follow-up data, baseline mTICS and demographic information predicted 9-31% of ILS subscale scores at follow-up. Conclusions: The mTICS appears able to predict daily functioning in older individuals with MCI. Remote tracking of cognition and daily functioning in this at-risk group seems particularly beneficial to geriatricians and other providers, especially during COVID-19.Item The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort(Wiley, 2023) Touroutoglou, Alexandra; Katsumi, Yuta; Brickhouse, Michael; Zaitsev, Alexander; Eckbo, Ryan; Aisen, Paul; Beckett, Laurel; Dage, Jeffrey L.; Eloyan, Ani; Foroud, Tatiana; Ghetti, Bernardino; Griffin, Percy; Hammers, Dustin; Jack, Clifford R., Jr.; Kramer, Joel H.; Iaccarino, Leonardo; La Joie, Renaud; Mundada, Nidhi S.; Koeppe, Robert; Kukull, Walter A.; Murray, Melissa E.; Nudelman, Kelly; Polsinelli, Angelina J.; Rumbaugh, Malia; Soleimani-Meigooni, David N.; Toga, Arthur; Vemuri, Prashanthi; Atri, Alireza; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Stephen; Sha, Sharon; Turner, R. Scott; Wingo, Thomas S.; Wolk, David A.; Womack, Kyle; Carrillo, Maria C.; Rabinovici, Gil D.; Apostolova, Liana G.; Dickerson, Bradford C.; LEADS Consortium; Neurology, School of MedicineIntroduction: Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. Methods: We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. Results: The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. Discussion: The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. Highlights: We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.Item White matter hyperintensities are higher among early-onset Alzheimer's disease participants than their cognitively normal and early-onset nonAD peers: Longitudinal Early-onset Alzheimer's Disease Study (LEADS)(Wiley, 2023) Eloyan, Ani; Thangarajah, Maryanne; An, Na; Borowski, Bret J.; Reddy, Ashritha L.; Aisen, Paul; Dage, Jeffrey L.; Foroud, Tatiana; Ghetti, Bernardino; Griffin, Percy; Hammers, Dustin; Iaccarino, Leonardo; Jack, Clifford R., Jr.; Kirby, Kala; Kramer, Joel; Koeppe, Robert; Kukull, Walter A.; La Joie, Renaud; Mundada, Nidhi S.; Murray, Melissa E.; Nudelman, Kelly; Rumbaugh, Malia; Soleimani-Meigooni, David N.; Toga, Arthur; Touroutoglou, Alexandra; Atri, Alireza; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph; Mendez, Mario F.; Musiek, Erik; Onyike, Chiadi U.; Rogalski, Emily; Salloway, Stephen; Sha, Sharon; Turner, Raymond S.; Wingo, Thomas S.; Wolk, David A.; Womack, Kyle; Beckett, Laurel; Gao, Sujuan; Carrillo, Maria C.; Rabinovici, Gil; Apostolova, Liana G.; Dickerson, Brad; Vemuri, Prashanthi; LEADS Consortium; Neurology, School of MedicineIntroduction: We compared white matter hyperintensities (WMHs) in early-onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early-onset amyloid-negative cognitively impaired (EOnonAD) groups in the Longitudinal Early-Onset Alzheimer's Disease Study. Methods: We investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t-tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden. Results: EOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group. Discussion: EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD. Highlights: This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early-onset amyloid-negative cognitively impaired (EOnonAD) groups across all brain regions.