Citations 2
Relationship between age and severity of cognitive impairment at diagnosis for early‐onset and late‐onset Alzheimer's disease: Comparison of LEADS and ADNI
Hammers, Dustin B., Eloyan, Ani, Thangarajah, Maryanne, Taurone, Alexander, Gao, Sujuan, Beckett, Laurel, Kirby, Kala, Dage, Jeffrey L., Nudelman, Kelly, Aisen, Paul, Reman, Rema, Vemuri, Prashanthi, Joie, Renaud La, Touroutoglou, Alexandra, Atri, Alireza, Clark, David, Day, Gregory S., Duara, Ranjan, Graff‐Radford, Neill R., Honig, Lawrence S., Jones, D., 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, Marı́a C., Dickerson, Bradford C., Rabinovici, Gil D., Apostolova, Liana G., Initiative, for the Alzheimer's Disease Neuroimaging, Carrillo, María C. , Rabinovici, Gil D. , Joie, Renaud La , Day, Gregory S. , Day, Gregory S , La Joie, Renaud , Rabinovici, Gil D , Hammers, Dustin B , Eloyan, Ani , Taurone, Alexander, Gao, Sujuan , Beckett, Laurel , Dage, Jeffrey L. , Nudelman, Kelly , Aisen, Paul , Reman, Rema, Vemuri, Prashanthi , Touroutoglou, Alexandra , Atri, Alireza , Clark, David, 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 , Johnson, Erik C. B. , Salloway, Steve , Turner, Raymond Scott , Wolk, David A. , Dickerson, Bradford Clark , Apostolova, Liana G. , Initiative, for the Alzheimer’s Disease Neuroimaging
Alzheimer's & Dementia | January 30, 2026 | Volume: 22 | Issue: 2 | Pages: No page available
INTRODUCTION Recent work has identified unique cognitive profiles for early‐onset Alzheimer's disease (EOAD) relative to late‐onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions. METHODS A series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein ε4 status. RESULTS Significant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non‐amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD. DISCUSSION In the age of disease‐modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same‐aged peers across most domains. Both groups displayed positive relationships between impairment among non‐amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.
Alzheimer's disease polygenic risk in early‐ and late‐onset Alzheimer's disease
Pentchev, Julian V., Jackson, Trever, Khan, Naazneen , Rosewood, Thea , Huang, Yen‐Ning, Nho, Kwangslk, Saykin, Andrew J., Eloyan, Ani, Taurone, Alexander, Thangarajah, Maryanne, Riddle, Meghan, Salloway, Steven, Atri, Alireza, Honig, Lawrence S., Johnson, Erik C. B., Turner, Raymond Scott, Masdeu, Joseph C. , Foroud, Tatiana M., Clark, David, Hammers, Dustin B., Dage, Jeffrey L., Kirby, Kala, Ghetti, Bernardino, Newell, Kathy, Onyike, Chiadi U., Day, Gregory S., Graff‐Radford, Neill R., Murray, Melissa E., Jones, D. Richard, Jack, Clifford R., Vemuri, Prashanthi, Touroutoglou, Alexandra, Duara, Ranjan, Grant, Ian, Sha, Sharon, Wingo, Thomas S., Beckett, Laurel A., Rogalski, Emily J, Mendez, Mario F., Kramer, Joel, Joie, Renaud La, Grinberg, Lea T., Koeppe, Robert, Wolk, David A., Aisen, Paul, RAMAN, REMA , Toga, Arthur, Kukull, Walter A., Musiek, Erik, Womack, Kyle, Carrillo, Maria C., Rabinovici, Gil D., Dickerson, Bradford C., Apostolova, Liana G., Nudelman, Kelly N. H., Murray, Melissa E. , Carrillo, María C. , Turner, Raymond Scott , Rabinovici, Gil D. , Joie, Renaud La , Day, Gregory S. , Day, Gregory S , Murray, Melissa E , La Joie, Renaud , Rabinovici, Gil D , Huang, Yen‐Ning, Nho, Kwangsik T. , Saykin, Andrew J. , Eloyan, Ani , Taurone, Alexander, Riddle, Meghan , Salloway, Steve , Atri, Alireza , Honig, Lawrence S. , Johnson, Erik C. B. , Masdeu, Joseph C , Foroud, Tatiana , Clark, David, Hammers, Dustin B , Dage, Jeffrey L. , Ghetti, Bernardino , Newell, Kathy L. , Onyike, Chiadi U. , Graff‐Radford, Neill R. , Jones, David T. , Jack, Clifford R. , Vemuri, Prashanthi , Touroutoglou, Alexandra , Duara, Ranjan , Sha, Sharon J. , Beckett, Laurel , Rogalskı, Emily , Mendez, Mario F. , Kramer, Joel, Blazhenets, Ganna , Grinberg, Lea T. , Koeppe, Robert A. , Wolk, David A. , Aisen, Paul , Toga, Arthur W. , Kukull, Walter A. , Musiek, Erik , Dickerson, Bradford Clark , Apostolova, Liana G. , Nudelman, Kelly
Alzheimer's & Dementia | January 14, 2026 | Volume: 22 | Issue: 1 | Pages: No page available
Abstract INTRODUCTION The genetic basis of sporadic early‐onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late‐onset Alzheimer's disease (LOAD) polygenic risk in EOAD. METHODS A LOAD polygenic score (PGS) was calculated in the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers. RESULTS Though PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset ( p = 0.106) or with cognitive performance ( p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal‐associated protein 25 (SNAP‐25) ( p = 2.3 × 10 −5 ). DISCUSSION While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology. Highlights LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal‐associated protein 25 (SNAP‐25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD.