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Authors: Beam, Christopher R. | Kaneshiro, Cody | Jang, Jung Yun | Reynolds, Chandra A. | Pedersen, Nancy L. | Gatz, Margaret

Article Type: Research Article

Abstract: Background: While sex differences in incidence of Alzheimer’s disease (AD) and potential explanations have received considerable attention, less attention has been paid to possible sex differences in genetic risk for AD. Objective: We examined sex differences in genetic and environmental influences on disease risk and age at onset for All Dementia, AD Only, and Non-AD Dementia. Methods: Twin pairs were drawn from the Swedish Twin Registry. All Dementia analysis included 9,467 pairs; AD only, 8,696 pairs; and non-AD dementia, 8,195 pairs. APOE analyses included 1,740 individual twins with measured ɛ 4 alleles. Dementia diagnoses were based on clinical workup and …national health registry linkage. Results: Although within-pair correlations for All Dementia and AD Only were higher for women than for men, sex differences did not statistically differ for genetic or environmental etiology of All Dementia, AD Only, and Non-AD dementia. Similar results were observed when looking at specific genetic effects (APOE ɛ 4). Co-twin control analyses indicated that among twin pairs discordant for dementia, female twins without dementia had approximately 40% greater risk of developing dementia, compared with their male counterparts, in the 2–5 years following the first twin’s diagnosis. Conclusion: For All Dementia, AD Only, and Non-AD Dementia, genetic influences could be equated across sex. Co-twin analyses, however, suggest greater risk to female than to male co-twins of dementia cases even though sex differences in either genetic or shared environmental influences on the risk of dementia could not be differentiated. Show more

Keywords: Alzheimer’s disease, APOE ɛ4, sex differences, twin studies

DOI: 10.3233/JAD-191192

Citation: Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 539-551, 2020

Authors: Beam, Christopher R. | Kaneshiro, Cody | Jang, Jung Yun | Reynolds, Chandra A. | Pedersen, Nancy L. | Gatz, Margaret

Article Type: Short Communication

Abstract: In the following brief report, we examined gender differences in incidence rates of any dementia, Alzheimer’s disease (AD) alone, and non-Alzheimer’s dementia alone in 16,926 women and men in the Swedish Twin Registry aged 65+. Dementia diagnoses were based on clinical workup and national health registry linkage. Incidence rates of any dementia and AD were greater in women than men, with any dementia rates diverging after age 85 and AD rates diverging around 80. This pattern is consistent with women’s survival to older ages compared to men. These findings are similar to incidence rates reported in other Swedish samples.

Keywords: Alzheimer’s disease, any dementia, gender differences, incidence, Swedish Twin Registry

DOI: 10.3233/JAD-180141

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1077-1083, 2018

Authors: Jang, Jung Yun | Ho, Jean K. | Blanken, Anna E. | Dutt, Shubir | Nation, Daniel A. | the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer’s disease (AD) pathophysiology. Objective: To investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality. Methods: Participants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ 4 …(ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months. Results: Latent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles. Conclusion: Findings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles. Show more

Keywords: Alzheimer’s disease, CSF biomarkers, dementia, neuropsychiatric symptoms

DOI: 10.3233/JAD-200190

Citation: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1195-1207, 2020

Authors: Nation, Daniel A. | Tan, Alick | Dutt, Shubir | McIntosh, Elissa C. | Yew, Belinda | Ho, Jean K. | Blanken, Anna E. | Jang, Jung Yun | Rodgers, Kathleen E. | Gaubert, Aimée

Article Type: Research Article

Abstract: Background: Bone marrow-derived progenitor cells survey the vasculature and home to sites of tissue injury where they can promote repair and regeneration. It has been hypothesized that these cells may play a protective role neurodegenerative and vascular cognitive impairment. Objective: To evaluate progenitor cell levels in older adults with and without mild cognitive impairment (MCI), and to relate circulating levels to memory, brain volume, white matter lesion volume, and cerebral perfusion. Method: Thirty-two older adults, free of stroke and cardiovascular disease, were recruited from the community and evaluated for diagnosis of MCI versus cognitively normal (CN). Participants underwent brain MRI …and blood samples were taken to quantify progenitor reserve using flow cytometry (CD34+, CD34+CD133+, and CD34+CD133+CD309+ cells). Results: Participants with MCI (n  = 10) exhibited depletion of all CPC markers relative to those who were CN (n  = 22), after controlling for age, sex, and education. Post-hoc age, sex, and education matched comparisons (n  = 10 MCI, n  = 10 CN) also revealed the same pattern of results. Depletion of CD34+ cells correlated with memory performance, left posterior cortical thickness, and bilateral hippocampal perfusion. Participants exhibited low levels of vascular risk and white matter lesion burden that did not correlate with progenitor levels. Conclusions: Circulating progenitor cells are associated with cognitive impairment, memory, cortical atrophy, and hippocampal perfusion. We hypothesize that progenitor depletion contributes to, or is triggered by, cognitive decline and cortical atrophy. Further study of progenitor cell depletion in older adults may benefit efforts to prevent or delay dementia. Show more

Keywords: Atrophy, cognitive dysfunction, memory, perfusion, stem cells

DOI: 10.3233/JAD-170587

Citation: Journal of Alzheimer's Disease, vol. 61, no. 1, pp. 91-101, 2018

Authors: Marshall, Anisa J. | Gaubert, Aimee | Kapoor, Arunima | Tan, Alick | McIntosh, Elissa | Jang, Jung Yun | Yew, Belinda | Ho, Jean K. | Blanken, Anna E. | Dutt, Shubir | Sible, Isabel J. | Li, Yanrong | Rodgers, Kathleen | Nation, Daniel A.

Article Type: Research Article

Abstract: Background: Depletion of blood-derived progenitor cells, including so called “early endothelial progenitor cells”, has been observed in individuals with early stage Alzheimer’s disease relative to matched older control subjects. These findings could implicate the loss of angiogenic support from hematopoietic progenitors or endothelial progenitors in cognitive dysfunction. Objective: To investigate links between progenitor cell proliferation and mild levels of cognitive dysfunction. Methods: We conducted in vitro studies of blood-derived progenitor cells using blood samples from sixty-five older adults who were free of stroke or dementia. Peripheral blood mononuclear cells from venous blood samples were cultured in CFU-Hill media and the …number of colony forming units were counted after 5 days in vitro . Neuropsychological testing was administered to all participants. Results: Fewer colony forming units were observed in samples from older adults with a Clinical Dementia Rating global score of 0.5 versus 0. Older adults whose samples developed fewer colony forming units exhibited worse performance on neuropsychological measures of memory, executive functioning, and language ability. Conclusion: These data suggest blood progenitors may represent a vascular resilience marker related to cognitive dysfunction in older adults. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, progenitor cells, vascular resilience

DOI: 10.3233/JAD-220269

Citation: Journal of Alzheimer's Disease, vol. 93, no. 3, pp. 1041-1050, 2023