Journal of Alzheimer's Disease - Volume 90, issue 1

Authors: Lachner, Christian | Day, Gregory S. | Camsari, Gamze Balci | Kouri, Naomi | Ertekin-Taner, Nilüfer | Boeve, Bradley F. | Labuzan, Sydney A. | Lucas, John A. | Thompson, E. Aubrey | Siddiqui, Habeeba | Crook, Julia E. | Cabrera-Rodriguez, Janisse N. | Josephs, Keith A. | Petersen, Ronald C. | Dickson, Dennis W. | Reichard, R. Ross | Mielke, Michelle M. | Knopman, David S. | Graff-Radford, Neill R. | Murray, Melissa E.

Article Type: Research Article

Abstract: Background: Dementia, vascular disease, and cancer increase with age, enabling complex comorbid interactions. Understanding vascular and cancer contributions to dementia risk and neuropathology in oldest-old may improve risk modification and outcomes. Objective: Investigate the contributions of vascular factors and cancer to dementia and neuropathology. Methods: Longitudinal clinicopathologic study of prospectively followed Mayo Clinic participants dying≥95 years-old who underwent autopsy. Participants were stratified by dementia status and compared according to demographics, vascular risk factors, cancer, and neuropathology. Results: Participants (n  = 161; 83% female; 99% non-Hispanic whites)≥95 years (95–106 years-old) with/without dementia did not differ based …on demographics. APOE ɛ2 frequency was higher in no dementia (20/72 [28%]) versus dementia (11/88 [12%]; p  = 0.03), but APOE ɛ4 frequency did not differ. Coronary artery disease was more frequent in no dementia (31/72 [43%]) versus dementia (23/89 [26%]; p  = 0.03) associated with 56% lower dementia odds (odds ratio [OR] = 0.44 [confidence interval (CI) = 0.19–0.98]; p  = 0.04) and fewer neuritic/diffuse plaques. Diabetes had an 8-fold increase in dementia odds (OR = 8.42 [CI = 1.39–163]; p  = 0.02). Diabetes associated with higher cerebrovascular disease (Dickson score; p  = 0.05). Cancer associated with 63% lower dementia odds (OR = 0.37 [CI = 0.17–0.78]; p  < 0.01) and lower Braak stage (p  = 0.01). Conclusion: Cancer exposure in the oldest-old was associated with lower odds of dementia and tangle pathology, whereas history of coronary artery disease was associated with lower odds of dementia and amyloid-β plaque pathology. History of diabetes mellitus was associated with increased odds of dementia and cerebrovascular disease pathology. Cancer-related mechanisms and vascular risk factor reduction strategies may alter dementia risk and neuropathology in oldest-old. Show more

Keywords: Aging, Alzheimer’s disease, cancer, dementia, neuropathology, vascular disease

DOI: 10.3233/JAD-220440

Citation: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 405-417, 2022

Authors: Baldeiras, Inês | Silva-Spínola, Anuschka | Lima, Marisa | Leitão, Maria João | Durães, João | Vieira, Daniela | Tábuas-Pereira, Miguel | Cruz, Vitor Tedim | Rocha, Raquel | Alves, Luisa | Machado, Álvaro | Milheiro, Miguel | Santiago, Beatriz | Santana, Isabel

Article Type: Research Article

Abstract: Background: The ATN scheme was proposed as an unbiased biological characterization of the Alzheimer’s disease (AD) spectrum, grouping biomarkers into three categories: brain Amyloidosis-A, Tauopathy-T, Neurodegeneration-N. Although this scheme was mainly recommended for research, it is relevant for diagnosis. Objective: To evaluate the ATN scheme performance in real-life cohorts reflecting the inflow of patients with cognitive complaints and different underlying disorders in general neurological centers. Methods: We included patients (n  = 1,128) from six centers with their core cerebrospinal fluid-AD biomarkers analyzed centrally. A was assessed through Aβ42 /Aβ40 , T through pTau-181, and N through tTau. …Association between demographic features, clinical diagnosis at baseline/follow-up and ATN profiles was assessed. Results: The prevalence of ATN categories was: A-T-N-: 28.3%; AD continuum (A  + T-/+N-/+): 47.8%; non-AD (A- plus T or/and N +): 23.9%. ATN profiles prevalence was strongly influenced by age, showing differences according to gender, APOE genotype, and cognitive status. At baseline, 74.6% of patients classified as AD fell in the AD continuum, decreasing to 47.4% in mild cognitive impairment and 42.3% in other neurodegenerative conditions. At follow-up, 41% of patients changed diagnosis, and 92% of patients that changed to AD were classified within the AD continuum. A  + was the best individual marker for predicting a final AD diagnosis, and the combinations A  + T+ (irrespective of N) and A  + T+N+ had the highest overall accuracy (83%). Conclusion: The ATN scheme is useful to guide AD diagnosis in real-life neurological centers settings. However, it shows a lack of accuracy for patients with other types of dementia. In such cases, the inclusion of other markers specific for non-AD proteinopathies could be an important aid to the differential diagnosis. Show more

Keywords: Alzheimer’s disease, ATN scheme, cerebrospinal fluid biomarkers, cognitive complaints

DOI: 10.3233/JAD-220587

Citation: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 419-432, 2022

Authors: Mattioli, Pietro | Pardini, Matteo | Girtler, Nicola | Brugnolo, Andrea | Orso, Beatrice | Donniaquio, Andrea | Calizzano, Francesco | Mancini, Raffaele | Massa, Federico | Terzaghi, Michele | Bauckneht, Matteo | Morbelli, Silvia | Sambuceti, Gianmario | Nobili, Flavio | Arnaldi, Dario

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) is a heterogeneous condition. Idiopathic REM sleep behavior disorder (iRBD) can be associated with MCI (MCI-RBD). Objective: To investigate neuropsychological and brain metabolism features of patients with MCI-RBD by comparison with matched MCI-AD patients. To explore their predictive value toward conversion to a full-blown neurodegenerative disease. Methods: Seventeen MCI-RBD patients (73.6±6.5 years) were enrolled. Thirty-four patients with MCI-AD were matched for age (74.8±4.4 years), Mini-Mental State Exam score and education with a case-control criterion. All patients underwent a neuropsychological assessment and brain 18 F-FDG-PET. Images were compared between groups to identify …hypometabolic volumes of interest (MCI-RBD-VOI and MCI-AD-VOI). The dependency of whole-brain scaled metabolism levels in MCI-RBD-VOI and MCI-AD-VOI on neuropsychological test scores was explored with linear regression analyses in both groups, adjusting for age and education. Survival analysis was performed to investigate VOIs phenoconversion prediction power. Results: MCI-RBD group scored lower in executive functions and higher in verbal memory compared to MCI-AD group. Also, compared with MCI-AD, MCI-RBD group showed relative hypometabolism in a posterior brain area including cuneus, precuneus, and occipital regions while the inverse comparison revealed relative hypometabolism in the hippocampus/parahippocampal areas in MCI-AD group. MCI-RBD-VOI metabolism directly correlated with executive functions in MCI-RBD (p  = 0.04). MCI-AD-VOI metabolism directly correlated with verbal memory in MCI-AD (p  = 0.001). MCI-RBD-VOI metabolism predicted (p  = 0.03) phenoconversion to an alpha-synucleinopathy. MCI-AD-VOI metabolism showed a trend (p  = 0.07) in predicting phenoconversion to dementia. Conclusion: MCI-RBD and MCI-AD showed distinct neuropsychological and brain metabolism profiles, that may be helpful for both diagnosis and prognosis purposes. Show more

Keywords: Alpha-synucleinopathies, Alzheimer’s disease, brain metabolism, mild cognitive impairment, REM sleep behavior disorder

DOI: 10.3233/JAD-220653

Citation: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 433-444, 2022

Authors: Sun, Lin | Li, Wei | Yue, Ling | Xiao, Shifu

Article Type: Correction

DOI: 10.3233/JAD-229011

Citation: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 445-445, 2022