Journal of Alzheimer's Disease - Volume 79, issue 2

Authors: Lage, Carmen | González-Suárez, Andrea | Alcalde-Hierro, María Puerto | Sampedro-González, María Isabel | Villanueva-Eguaras, María Ángeles | Sánchez-Crespo, Manuel Rubén | Widmann, Catherine | Brosseron, Frederic | Pozueta, Ana | López-García, Sara | García-Martínez, María | Kazimierczak, Martha | Bravo-González, María | Fernández-Rodríguez, Andrea | Drake-Pérez, Marta | Irure-Ventura, Juan | López-Hoyos, Marcos | Rodríguez-Rodríguez, Eloy | Heneka, Michael T. | Sánchez-Juan, Pascual

Article Type: Research Article

Abstract: Background: Major surgery has been associated with perioperative neurocognitive disorders (PND), but the contributing factors and long-term prognosis are uncertain. We hypothesize that preclinical Alzheimer’s disease (AD) might predispose to cognitive deterioration after surgery. Objective: To analyze the effect of amyloid-β on the cognitive trajectory after orthopedic surgery in a sample of non-demented subjects. Methods: Non-demented individuals older than 65 years that were on the waiting list for orthopedic surgery with spinal anesthesia underwent a neuropsychological assessment before and after surgery. During surgery, cerebrospinal fluid samples were obtained to determine AD biomarkers. Results: Cumulative …incidence of PND was 55.2%during a mean follow-up of nine months. The most affected cognitive domains were executive function and constructional praxis. The presence of abnormal levels of amyloid-β was associated to a postoperative impairment in verbal and visual memory tests. According to their AD biomarker profile, participants were categorized as either Amyloid Positive (A +) or Amyloid Negative (A-). The incidence of PND did not differ between both groups. The A- group showed a tendency similar to the global sample, worsening in executive function tests and improving on memory scales due to practice effects. In contrast, the A  + group showed a notable worsening on memory performance. Conclusion: Our findings support the hypothesis that surgery may promote or accelerate memory decline in cognitively asymptomatic subjects with brain amyloid-β deposits. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, biomarkers, dementia, surgery

DOI: 10.3233/JAD-191229

Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 863-874, 2021

Authors: Gabrielyan, Lilit | Liang, Honghui | Minalyan, Artem | Hatami, Asa | John, Varghese | Wang, Lixin

Article Type: Research Article

Abstract: Background: Alpha-synuclein (α -syn) is involved in pathology of Parkinson’s disease, and 90% of α -syn in Lewy bodies is phosphorylated at serine 129 (pS129 α -syn). Objective: To assess behavior impairments and brain levels of α -syn and pS129 α -syn in mice overexpressing human α -syn under Thy1 promoter (Thy1-α -syn) and wild type (wt) littermates. Methods: Motor and non-motor behaviors were monitored, brain human α -syn levels measured by ELISA, and α -syn and pS129 α -syn mapped by immunohistochemistry. Results: Male and female wt littermates did not show differences in …the behavioral tests. Male Thy1-α -syn mice displayed more severe impairments than female counterparts in cotton nesting, pole tests, adhesive removal, finding buried food, and marble burying. Concentrations of human α -syn in the olfactory regions, cortex, nigrostriatal system, and dorsal medulla were significantly increased in Thy1-α -syn mice, higher in males than females. Immunoreactivity of α -syn was not simply increased in Thy1-α -syn mice but had altered localization in somas and fibers in a few brain areas. Abundant pS129 α -syn existed in many brain areas of Thy1-α -syn mice, while there was none or only a small amount in a few brain regions of wt mice. The substantia nigra, olfactory regions, amygdala, lateral parabrachial nucleus, and dorsal vagal complex displayed different distribution patterns between wt and transgenic mice, but not between sexes. Conclusion: The severer abnormal behaviors in male than female Thy1-α -syn mice may be related to higher brain levels of human α -syn, in the absence of sex differences in the altered brain immunoreactivity patterns of α -syn and pS129 α -syn. Show more

Keywords: α-synuclein, behavior, brain, mouse, phosphorylated serine-129 α-synuclein, synucleinopathy

DOI: 10.3233/JAD-200983

Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 875-893, 2021

Authors: Chatterjee, Pratishtha | Fagan, Anne M. | Xiong, Chengjie | McKay, Matthew | Bhatnagar, Atul | Wu, Yunqi | Singh, Abhay K. | Taddei, Kevin | Martins, Ian | Gardener, Samantha L. | Molloy, Mark P. | Multhaup, Gerhard | Masters, Colin L. | Schofield, Peter R. | Benzinger, Tammie L.S. | Morris, John C. | Bateman, Randall J. | Greenberg, Steven M. | Wermer, Marieke J.H. | van Buchem, Mark A. | Sohrabi, Hamid R. | Martins, Ralph N. | Dominantly Inherited Alzheimer Network

Article Type: Research Article

Abstract: Background: Cerebral amyloid angiopathy (CAA) is one of the major causes of intracerebral hemorrhage and vascular dementia in older adults. Early diagnosis will provide clinicians with an opportunity to intervene early with suitable strategies, highlighting the importance of pre-symptomatic CAA biomarkers. Objective: Investigation of pre-symptomatic CAA related blood metabolite alterations in Dutch-type hereditary CAA mutation carriers (D-CAA MCs). Methods: Plasma metabolites were measured using mass-spectrometry (AbsoluteIDQ® p400 HR kit) and were compared between pre-symptomatic D-CAA MCs (n = 9) and non-carriers (D-CAA NCs, n = 8) from the same pedigree. Metabolites that survived correction …for multiple comparisons were further compared between D-CAA MCs and additional control groups (cognitively unimpaired adults). Results: 275 metabolites were measured in the plasma, 22 of which were observed to be significantly lower in theD-CAAMCs compared to D-CAA NCs, following adjustment for potential confounding factors age, sex, and APOE ε 4 (p  < 0.05). After adjusting for multiple comparisons, only spermidine remained significantly lower in theD-CAAMCscompared to theD-CAA NCs (p  < 0.00018). Plasma spermidine was also significantly lower in D-CAA MCs compared to the cognitively unimpaired young adult and older adult groups (p  < 0.01). Spermidinewas also observed to correlate with CSF Aβ40 (rs = 0.621, p = 0.024), CSF Aβ42 (rs = 0.714, p = 0.006), and brain Aβ load (rs = –0.527, p  = 0.030). Conclusion: The current study provides pilot data on D-CAA linked metabolite signals, that also associated with Aβ neuropathology and are involved in several biological pathways that have previously been linked to neurodegeneration and dementia. Show more

Keywords: Blood biomarkers, cerebral amyloid angiopathy, early diagnosis, hereditary cerebral hemorrhage with amyloidosis - dutch type, intracerebral hemorrhage, metabolomics, vascular dementia

DOI: 10.3233/JAD-201267

Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 895-903, 2021

Authors: Hoang, Minh Tuan | Kåreholt, Ingemar | von Euler, Mia | von Koch, Lena | Eriksdotter, Maria | Garcia-Ptacek, Sara

Article Type: Research Article

Abstract: Background: Patient dissatisfaction with stroke care is associated with poor self-rated health and unmet care needs. Dementia patients’ satisfaction with stroke care is understudied. Objective: To compare satisfaction with stroke care in patients with and without dementia. Methods: This longitudinal cohort study included 5,932 dementia patients (2007–2017) who suffered a first stroke after dementia diagnosis and 39,457 non-dementia stroke patients (2007–2017). Data were retrieved by linking the Swedish Stroke Register, the Swedish Dementia Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. The association between dementia and satisfaction was analyzed with ordinal logistic …regression. Results: When dementia patients answered themselves, they reported significantly lower odds of satisfaction with acute stroke care (OR: 0.71; 95% CI: 0.60–0.85), healthcare staff’s attitude (OR: 0.79; 95% CI: 0.66–0.96), communication with doctors (OR: 0.78; 95% CI: 0.66–0.92), stroke information (OR: 0.62; 95% CI: 0.52–0.74); but not regarding inpatient rehabilitation (OR: 0.93; 95% CI: 0.75–1.16), or outpatient rehabilitation (OR: 0.93; 95% CI: 0.73–1.18). When patients answered with caregivers’ help, the association between dementia status and satisfaction remained significant in all items. Subgroup analyses showed that patients with Alzheimer’s disease and mixed dementia reported lower odds of satisfaction with acute care and healthcare staff’s attitude when they answered themselves. Conclusion: Patients with dementia reported lower satisfaction with stroke care, revealing unfulfilled care needs among dementia patients, which are possibly due to different (or less) care, or because dementia patients require adaptations to standard care. Show more

Keywords: Care, dementia, patient-reported, rehabilitation, satisfaction, stroke

DOI: 10.3233/JAD-200976

Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 905-916, 2021

Authors: Tromp, Krista | Smedinga, Marthe | Richard, Edo | Perry, Marieke | Schermer, Maartje H.N.

Article Type: Research Article

Abstract: Background: Hope for future treatments to prevent or slow down dementia motivates researchers to strive for ever-earlier diagnoses of Alzheimer’s disease (AD) based on biomarkers, even before symptoms occur. But is a biomarker-based early diagnosis desirable in clinical practice? Objective: This study explores the ethical considerations that shape current clinical practice regarding early AD diagnostics and the use of biomarkers. Methods: In this qualitative study, Dutch physicians were interviewed. Topics included physicians’ views concerning early AD diagnosis in persons with no or mild cognitive impairment, physicians’ considerations regarding current and expected future practices of early AD …diagnosis, the use of biomarkers, and the use of the concepts preclinical and prodromal AD. We analyzed the transcripts using directed content analysis. Results: 15 general practitioners, neurologists, and geriatricians in the Netherlands were interviewed. Most of them interpreted an early AD diagnosis with an early diagnosis of dementia. We identified six clusters of considerations sometimes in favor but most often against pursuing an early AD diagnosis in people with no or mild cognitive impairment that influence physicians’ diagnostic decision-making: preferences and characteristics of persons, test characteristics, impact on care, type of setting, disease concepts, and issues on a societal level. Conclusion: The discussion concerning an early AD diagnosis based on biomarkers which is widely held in the scientific field, has not entered clinical practice structurally. A biomarker-based early diagnosis does not fit within Dutch physicians’ views on what good care for people with no, subjective, or mild cognitive impairment should entail. Show more

Keywords: Alzheimer’s disease, biomarkers, decision-making, early diagnosis, ethics

DOI: 10.3233/JAD-200884

Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 917-927, 2021

Authors: Waki, Takashi | Tanaka-Mizuno, Sachiko | Takashima, Naoyuki | Takechi, Hajime | Hayakawa, Takehito | Miura, Katsuyuki | Ueshima, Hirotsugu | Kita, Yoshikuni | Dodge, Hiroko H.

Article Type: Correction

DOI: 10.3233/JAD-209011

Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 929-930, 2021