Journal of Alzheimer's Disease - Volume 81, issue 1

Authors: Fonseca, Luciana Mascarenhas | Mattar, Guilherme Prado | Haddad, Glenda Guerra | Burduli, Ekaterina | McPherson, Sterling M. | Guilhoto, Laura Maria de Figueiredo Ferreira | Yassuda, Mônica Sanches | Busatto, Geraldo Filho | Bottino, Cassio Machado de Campos | Hoexter, Marcelo Queiroz | Chaytor, Naomi Sage

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Objective: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). Methods: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities …(CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Results: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p  = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2  = 0.627, F(15,76) = 8.510, p  < 0.001). Conclusion: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms. Show more

Keywords: Alzheimer’s disease, dementia, Down syndrome, intellectual disability, Neuropsychiatric Inventory, neuropsychiatric symptoms

DOI: 10.3233/JAD-201009

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 137-154, 2021

Authors: Bai, Dong | Fan, Junting | Li, Mengyue | Dong, Cuixia | Gao, Yiming | Fu, Min | Huang, Guowei | Liu, Huan

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked “RETRACTED”. A retraction notice is available at DOI: 10.3233/JAD-239002 .

DOI: 10.3233/JAD-200997

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 155-167, 2021

Authors: Baptista, Maria Alice Tourinho | Kimura, Nathália | Lacerda, Isabel Barbeito | Silva, Felipe de Oliveira | Dourado, Marcia Cristina Nascimento

Article Type: Research Article

Abstract: Background: There is a lack of research investigating whether there are differences in the domains of awareness according to the age at onset of dementia. Objective: This study is designed to investigate differences in awareness of cognitive functioning and health condition, functional activity impairments, emotional state, and social functioning and relationships among people with young onset (YOD) and late onset dementia (LOD); and examine associations between awareness and its domains with cognition, functionality, neuropsychiatric symptoms, social and emotional functioning, and quality of life (QoL) in both groups. Methods: A group of 136 people with dementia and …their respective caregivers (YOD = 50 and LOD = 86) were consecutively selected. We assessed awareness of disease, dementia severity, cognition, functionality, neuropsychiatric symptoms, social and emotional functioning, and QoL. Results: People with YOD had more neuropsychiatric symptoms than people with LOD. People with YOD were more aware of disease (total score), of their cognitive functioning and health condition and of their functional activity impairments, even if this group was more severely cognitive impaired and had a worse level of functionality than LOD group. Multivariate linear regressions showed that functionality has a wide relationship to awareness for people with YOD. While neuropsychiatric symptoms and QoL has a greater relation to awareness for people with LOD. Conclusion: Different clinical variables are associated to different domains in YOD and LOD groups, reinforcing the heterogeneity of awareness in dementia. Show more

Keywords: Awareness of disease, awareness’ domains, dementia, late onset, young onset

DOI: 10.3233/JAD-201603

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 169-178, 2021

Authors: Schwertner, Emilia | Zelic, Renata | Secnik, Juraj | Johansson, Björn | Winblad, Bengt | Eriksdotter, Maria | Religa, Dorota

Article Type: Research Article

Abstract: Background: In Sweden, 2,296,000 firearms were legally owned by private persons in 2017 and there were 150,000 persons living with a dementia diagnosis. A proportion of these persons owning a firearm may pose safety concerns. Objective: The aim was to describe firearm ownership in persons with dementia in Sweden and examine which characteristics are explaining physicians’ decision to report a person to the police as unsuitable to possess a firearm. Methods: This was a registry-based observational study. 65,717 persons with dementia registered in the Swedish Dementia Registry were included in the study. Logistic regression was used …to evaluate which of the persons’ characteristics were most important in predicting the likelihood of being reported as unsuitable to possess a firearm. Relative importance of predictors was quantified using standardized coefficients (SC) and dominance analysis (DA). Results: Out of 53,384 persons with dementia, 1,823 owned a firearm and 419 were reported to the police as unsuitable owners. Firearm owners were predominantly younger, males, living alone, and without assistance of homecare. The most important predictors of being reported to the police were: living with another person (SC = 0.23), frontotemporal dementia (SC = 0.18), antipsychotics prescription (SC = 0.18), being diagnosed in a memory/cognitive clinic (SC = –0.27), female gender (SC = 0.18), mild (SC = –0.25) and moderate (SC = –0.21) dementia, and hypnotics prescription (SC = 0.17). Conclusion: Firearm owners with dementia were mostly younger males who were still living more independent lives. The decision to remove a weapon was not solely based on a diagnosis of dementia but a combination of factors was considered. Show more

Keywords: Alzheimer’s disease, behavioral and psychological symptoms of dementia, dementia, firearm, frontotemporal, neuropsychiatric symptoms, risk assessment, vascular, violence

DOI: 10.3233/JAD-201365

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 179-188, 2021

Authors: Kadey, Kylie R. | Woodard, John L. | Moll, Allison C. | Nielson, Kristy A. | Smith, J. Carson | Durgerian, Sally | Rao, Stephen M.

Article Type: Research Article

Abstract: Background: Body mass index (BMI) has been identified as an important modifiable lifestyle risk factor for dementia, but less is known about how BMI might interact with Apolipoprotein E ɛ4 (APOE ɛ4) carrier status to predict conversion to mild cognitive impairment (MCI) and dementia. Objective: The aim of this study was to investigate the interaction between APOE ɛ4 status and baseline (b BMI) and five-year BMI change (Δ BMI) on conversion to MCI or dementia in initially cognitively healthy older adults. Methods: The associations between b BMI, Δ BMI, APOE ɛ4 status, and …conversion to MCI or dementia were investigated among 1,289 cognitively healthy elders from the National Alzheimer’s Coordinating Center (NACC) database. Results: After five years, significantly more carriers (30.6%) converted to MCI or dementia than noncarriers (17.6%), p  < 0.001, OR  = 2.06. Neither b BMI (OR = 0.99, 95%CI = 0.96–1.02) nor the b BMI by APOE interaction (OR = 1.02, 95%CI = 0.96–1.08) predicted conversion. Although Δ BMI also did not significantly predict conversion (OR = 0.90, 95%CI = 0.78–1.04), the interaction between Δ BMI and carrier status was significant (OR = 0.72, 95%CI = 0.53–0.98). For carriers only, each one-unit decline in BMI over five years was associated with a 27%increase in the odds of conversion (OR = 0.73, 95%CI = 0.57–0.94). Conclusion: A decline in BMI over five years, but not b BMI, was strongly associated with conversion to MCI or dementia only for APOE ɛ4 carriers. Interventions and behaviors aimed at maintaining body mass may be important for long term cognitive health in older adults at genetic risk for AD. Show more

Keywords: Alzheimer’s disease, Apolipoprotein E4, body mass index, cognitive dysfunction, dementia

DOI: 10.3233/JAD-201360

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 189-199, 2021

Authors: Tong, Qiang | Chen, Liam

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the two most prevalent neurodegenerative diseases associated with age. Pathological studies have shown that these two diseases share a certain degree of neuropathological overlap. AD neuropathologic change contributes to cognitive impairment in PD. However, the impact of AD pathology on other clinical phenotypes in PD remains largely unknown. Objective: Herein we aimed to assess the impact of co-occurring AD neuropathologic change on the clinical phenotypes of PD. Methods: We examined 46 autopsy brains of PD patients and available clinical information to retrospectively assess the effects of comorbid …AD pathology on dementia, hallucinations, and dyskinesia commonly seen in advanced PD. Results: AD neuropathology significantly increased the risk of hallucinations and dementia, but not dyskinesia in PD patients. Surprisingly, diffuse Lewy body pathology, but not AD pathology, was associated with the occurrence of dementia and hallucinations. Most importantly, we reported that the severity of neuronal loss in the locus coeruleus (LC), but not the severity of neuronal loss in the substantia nigra (SN), was associated with the occurrence of dyskinesia in advanced PD patients, while neither Lewy body scores in SN nor LC had significant effects. Conclusion: We show for the first time that neuronal loss in LC contributes to dyskinesia. Understanding the relationships between the two distinct pathologies and their relevant clinical phenotypes will be crucial in the development of effective disease-modifying therapies for PD. Show more

Keywords: Alzheimer’s disease neuropathologic change, dementia, dyskinesia, hallucination, locus coeruleus, Parkinson’s disease

DOI: 10.3233/JAD-210114

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 201-207, 2021

Authors: Stonnington, Cynthia M. | Wu, Jianfeng | Zhang, Jie | Shi, Jie | Bauer III, Robert J. | Devadas, Vivek | Su, Yi | Locke, Dona E.C. | Reiman, Eric M. | Caselli, Richard J. | Chen, Kewei | Wang, Yalin | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Besides their other roles, brain imaging and other biomarkers of Alzheimer’s disease (AD) have the potential to inform a cognitively unimpaired (CU) person’s likelihood of progression to mild cognitive impairment (MCI) and benefit subject selection when evaluating promising prevention therapies. We previously described that among baseline FDG-PET and MRI measures known to be preferentially affected in the preclinical and clinical stages of AD, hippocampal volume was the best predictor of incident MCI within 2 years (79%sensitivity/78%specificity), using standard automated MRI volumetric algorithmic programs, binary logistic regression, and leave-one-out procedures. Objective: To improve the same prediction by using …different hippocampal features and machine learning methods, cross-validated via two independent and prospective cohorts (Arizona and ADNI). Methods: Patch-based sparse coding algorithms were applied to hippocampal surface features of baseline TI-MRIs from 78 CU adults who subsequently progressed to amnestic MCI in approximately 2 years (“progressors”) and 80 matched adults who remained CU for at least 4 years (“nonprogressors”). Nonprogressors and progressors were matched for age, sex, education, and apolipoprotein E4 allele dose. We did not include amyloid or tau biomarkers in defining MCI. Results: We achieved 92%prediction accuracy in the Arizona cohort, 92%prediction accuracy in the ADNI cohort, and 90%prediction accuracy when combining the two demographically distinct cohorts, as compared to 79%(Arizona) and 72%(ADNI) prediction accuracy using hippocampal volume. Conclusion: Surface multivariate morphometry and sparse coding, applied to individual MRIs, may accurately predict imminent progression to MCI even in the absence of other AD biomarkers. Show more

Keywords: Alzheimer’s disease, magnetic resonance imaging, mild cognitive impairment, prediction, prognosis

DOI: 10.3233/JAD-200821

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 209-220, 2021

Authors: Gao, Dandan | Shang, Junkui | Sun, Ruihua | Shi, Yingying | Jiang, Haisong | Ma, Mingming | Zhang, Jiewen

Article Type: Research Article

Abstract: Background: Exosomes are nano-sized extracellular vesicles which are secreted by cells and usually found in body fluids. Previous research has shown that exosomal secretion and autophagy-lysosomal pathway synergistically participates in intracellular abnormal protein elimination. The main pathological manifestations of Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is abnormal accumulation of mutant NOTCH3, and CADASIL vascular smooth muscle cells have been found with autophagy-lysosomal dysfunction. However, whether plasma exosomes change in CADASIL patients is still unclear. Objective: We are aimed to investigate the differences of plasma exosomes between CADASIL patients and healthy controls. Methods: …The subjects included 30 CADASIL patients and 30 healthy controls without NOTCH3 mutation. The severity of white matter lesions (WMLs) of CADASIL patients was quantified by Fazekas score. Transmission electron microscopy and nanoparticle tracking analysis were performed to characterize plasma exosomes. In addition, NOTCH3, Neurofilament light and Aβ42 levels in plasma exosomes were quantified by enzyme-linked immunosorbent assays. Results: We found that exosomes from CADASIL patients were lower in quantity. In addition, CADASIL plasma exosomes had significantly lower levels of NOTCH3 and significantly increased levels of NFL than those of matched healthy subjects. Interestingly, plasma exosome NOTCH3 levels of CADASIL patients significantly correlated with severity of WMLs. Conclusion: The exosome NOTCH3 may be related to the pathological changes of CADASIL, which provides a basis for the pathogenesis research of CADASIL. In addition, plasma exosome NOTCH3 and NFL levels may act as biomarkers to monitor and predict disease progression and measure therapeutic effectiveness in the future clinical trials. Show more

Keywords: CADASIL, exosomes, nanoparticle tracking analysis, neurofilament light, NOTCH3, transmission electron microscopy

DOI: 10.3233/JAD-210101

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 221-229, 2021

Authors: Teitsdottir, Unnur D. | Halldorsson, Skarphedinn | Rolfsson, Ottar | Lund, Sigrun H. | Jonsdottir, Maria K. | Snaedal, Jon | Petersen, Petur H.

Article Type: Research Article

Abstract: Background: Understanding how dysregulation in lipid metabolism relates to the severity of Alzheimer‘s disease (AD) pathology might be critical in developing effective treatments. Objective: To identify lipid species in cerebrospinal fluid (CSF) associated with signature AD pathology and to explore their relationships with measures reflecting AD-related processes (neurodegeneration, inflammation, deficits in verbal episodic memory) among subjects at the pre- and early symptomatic stages of dementia. Methods: A total of 60 subjects that had been referred to an Icelandic memory clinic cohort were classified as having CSF AD (n  = 34) or non-AD (n  = 26) pathology profiles. …Untargeted CSF lipidomic analysis was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) for the detection of mass-to-charge ratio (m/z) features. CSF proteins reflecting neurodegeneration (neurofilament light [NFL]) and inflammation (chitinase-3-like protein 1 [YKL-40], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein [GFAP]) were also measured. Rey Auditory Verbal Learning (RAVLT) and Story tests were used for the assessment of verbal episodic memory. Results: Eight out of 1008 features were identified as best distinguishing between the CSF profile groups. Of those, only the annotation of the m/z feature assigned to lipid species C18 ceramide was confirmed with a high confidence. Multiple regression analyses, adjusted for age, gender, and education, demonstrated significant associations of CSF core AD markers (Aβ42 : st.β= –0.36, p  = 0.007; T-tau: st.β= 0.41, p  = 0.005) and inflammatory marker S100B (st.β= 0.51, p  = 0.001) with C18 ceramide levels. Conclusion: Higher levels of C18 ceramide associated with increased AD pathology and inflammation, suggesting its potential value as a therapeutic target. Show more

Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid, inflammation, lipidomics

DOI: 10.3233/JAD-200964

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 231-244, 2021

Authors: Lee, Cecilia S. | Lee, Michael L. | Gibbons, Laura E. | Yanagihara, Ryan T. | Blazes, Marian | Kam, Jason P. | McCurry, Susan M. | Bowen, James D. | McCormick, Wayne C. | Lee, Aaron Y. | Larson, Eric B. | Crane, Paul K.

Article Type: Research Article

Abstract: Background: Vascular disease is a risk factor for Alzheimer’s disease (AD) and related dementia in older adults. Retinal artery/vein occlusion (RAVO) is an ophthalmic complication of systemic vascular pathology. Whether there are associations between RAVO and dementia risk is unknown. Objective: To determine whether RAVOs are associated with an increased risk of developing vascular dementia or AD. Methods: Data from Adult Changes in Thought (ACT) study participants were analyzed. This prospective, population-based cohort study followed older adults (age ≥65 years) who were dementia-free at enrollment for development of vascular dementia or AD based on research criteria. …RAVO diagnoses were extracted from electronic medical records. Cox-regression survival analyses were stratified by APOE ɛ 4 genotype and adjusted for demographic and clinical factors. Results: On review of 41,216 person-years (4,743 participants), 266 (5.6%) experienced RAVO. APOE ɛ 4 carriers who developed RAVO had greater than four-fold higher risk for developing vascular dementia (Hazard Ratio [HR] 4.54, 95% Confidence Interval [CI] 1.86, 11.10, p  = 0.001). When including other cerebrovascular disease (history of carotid endarterectomy or transient ischemic attack) in the model, the risk was three-fold higher (HR 3.06, 95% CI 1.23, 7.62). No other conditions evaluated in the secondary analyses were found to confound this relationship. There was no effect in non-APOE ɛ 4 carriers (HR 1.03, 95% CI 0.37, 2.80). There were no significant associations between RAVO and AD in either APOE group. Conclusion: Older dementia-free patients who present with RAVO and carry the APOE ɛ 4 allele appear to be at higher risk for vascular dementia. Show more

Keywords: Alzheimer’s disease, cohort study, epidemiology, retinal artery occlusion, retinal vascular occlusion, retinal vein occlusion, vascular dementia

DOI: 10.3233/JAD-201492

Citation: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 245-253, 2021