Browsing by Author "Grant, Ian"

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    Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials
    (Springer, 2025) Hammers, Dustin B.; Musema, Jane; Eloyan, Ani; Thangarajah, Maryanne; Taurone, Alexander; La Joie, Renaud; Touroutoglou, Alexandra; Vemuri, Prashanthi; Kramer, Joel; Aisen, Paul; Dage, Jeffrey L.; Nudelman, Kelly N.; Kirby, Kala; Atri, Alireza; Clark, David; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Grant, Ian; Honig, Lawrence S.; Johnson, Erik C. B.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Womack, Kyle; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Steven; Sha, Sharon J.; Scott Turner, Raymond; Wingo, Thomas S.; Wolk, David A.; Carrillo, Maria C.; Rabinovici, Gil D.; Dickerson, Bradford C.; Apostolova, Liana G.; LEADS Consortium; Neurology, School of Medicine
    Background: As literature suggests that Early-Onset Alzheimer's Disease (EOAD) and late-onset AD may differ in important ways, need exists for randomized clinical trials for treatments tailored to EOAD. Accurately measuring reliable cognitive change in individual patients with EOAD will have great value for these trials. Objectives: The current study sought to characterize and validate 12-month reliable change from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) neuropsychological battery. Design: Standardized regression-based (SRB) prediction equations were developed from age-matched cognitively intact participants within LEADS, and applied to clinically impaired participants from LEADS. Setting: Participants were recruited from outpatient academic medical centers. Participants: Participants were enrolled in LEADS and diagnosed with amyloid-positive EOAD (n = 189) and amyloid-negative early-onset cognitive impairment not related to AD (EOnonAD; n = 43). Measurement: 12-month reliable change (Z-scores) was compared between groups across cognitive domain composites, and distributions of individual participant trajectories were examined. Prediction of Z-scores by common AD biomarkers was also considered. Results: Both EOAD and EOnonAD displayed significantly lower 12-month follow-up scores than were predicted based on SRB equations, with declines more pronounced for EOAD across several domains. AD biomarkers of cerebral β-amyloid, tau, and EOAD-specific atrophy were predictive of 12-month change scores. Conclusions: The current results support including EOAD patients in longitudinal clinical trials, and generate evidence of validation for using 12-month reliable cognitive change as a clinical outcome metric in clinical trials in EOAD cohorts like LEADS. Doing so will enhance the success of EOAD trials and permit a better understanding of individual responses to treatment.
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    Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI
    (Wiley, 2025) Hammers, Dustin B.; Eloyan, Ani; Thangarajah, Maryanne; Taurone, Alexander; Beckett, Laurel; Gao, Sujuan; Polsinelli, Angelina J.; Kirby, Kala; Dage, Jeffrey L.; Nudelman, Kelly; Aisen, Paul; Reman, Rema; La Joie, Renaud; Lagarde, Julien; Atri, Alireza; Clark, David; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Honig, Lawrence S.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Womack, Kyle; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Grant, Ian; Rogalski, Emily; Johnson, Erik C. B.; Salloway, Steven; Sha, Sharon J.; Turner, Raymond Scott; Wingo, Thomas S.; Wolk, David A.; Carrillo, Maria C.; Dickerson, Bradford C.; Rabinovici, Gil D.; Apostolova, Liana G.; LEADS Consortium 1 for the Alzheimer's Disease Neuroimaging Initiative; Neurology, School of Medicine
    Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD. Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts. Z-score composites were compared between AD groups for each domain. Results: After controlling for cognitive status, EOAD displayed worse visuospatial, executive functioning, and processing speed/attention skills relative to LOAD, and LOAD displayed worse language, episodic immediate memory, and episodic delayed memory. Discussion: Sporadic EOAD possesses distinct cognitive profiles relative to LOAD. Clinicians should be alert for non-amnestic impairments in younger patients to ensure proper identification and intervention using disease-modifying treatments. Highlights: Both early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants displayed widespread cognitive impairments relative to their same-aged peers. Cognitive impairments were more severe for EOAD than for LOAD participants in visuospatial and executive domains. Memory and language impairments were more severe for LOAD than for EOAD participants Results were comparable after removing clinical phenotypes of posterior cortical atrophy (PCA), primary progressive aphasia (lv-PPA), and frontal-variant AD.
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    Longitudinal cognitive performance of participants with sporadic early onset Alzheimer's disease from LEADS
    (Wiley, 2025) Hammers, Dustin B.; Eloyan, Ani; Taurone, Alexander; Thangarajah, Maryanne; Gao, Sujuan; Beckett, Laurel; Polsinelli, Angelina J.; Kirby, Kala; Dage, Jeffrey L.; Nudelman, Kelly; Aisen, Paul; Reman, Rema; La Joie, Renaud; Lagarde, Julien; Atri, Alireza; Clark, David; Day, Gregory S.; Duara, Ranjan; Graff-Radford, Neill R.; Grant, Ian; Honig, Lawrence S.; Johnson, Erik C. B.; Jones, David T.; Masdeu, Joseph C.; Mendez, Mario F.; Womack, Kyle; Musiek, Erik; Onyike, Chiadi U.; Riddle, Meghan; Rogalski, Emily; Salloway, Steven; Sha, Sharon J.; Turner, Raymond Scott; Wingo, Thomas S.; Wolk, David A.; Carrillo, Maria C.; Rabinovici, Gil D.; Dickerson, Bradford C.; Apostolova, Liana G.; LEADS Consortium; Neurology, School of Medicine
    Introduction: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia. Methods: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared. Cognitive trajectories across a comprehensive cognitive battery spanning 42 months were examined using mixed-effects modeling. Results: The EOAD group displayed worse cognition at baseline relative to EOnonAD and CN groups, and more aggressive declines in cognition over time. The largest effects were observed on measures of executive functioning domains, while memory declines were blunted in EOAD. Discussion: EOAD declined 2-4× faster than EOnonAD, and EOAD pathology is not restricted to memory networks. Early identification of deficits is critical to ensure that individuals with sporadic EOAD can be considered for treatment using disease-modifying medications. Highlights: Represents the most comprehensive longitudinal characterization of sporadic EOAD to date. The trajectory of cognitive declines was steep for EOAD participants and worse than for other groups. Executive functioning measures exhibited the greatest declines over time in EOAD.