Journal of Alzheimer's Disease Reports - Volume 6, issue 1

Authors: Okolichany, Ronald | Padala, Prasad R. | Mooney, Scott

Article Type: Case Report

Abstract: Background: A 76-year-old male Veteran with a historical diagnosis of mild cognitive impairment was assessed at baseline and follow-up as part of two separate, ongoing studies. He was diagnosed with COVID-19 during the interim. Objective: To report potential effects on cognitive and functional abilities measured before and after contracting COVID-19. Methods: The patient was administered a series of cognitive tests and self-report procedures assessing cognitive, functional, and neuropsychiatric status. Results: Overall, no discernable pattern of cognitive changes between pre-COVID and post-COVID assessments were noted. Only mild increases in agitation, depression, and irritability were noted …on a self-report measure. However, this particular subject has relatively ideal psychosocial circumstances in comparison to the typical older adult Veteran male. It is hypothesized that improved psychosocial conditions will result in less negative cognitive and functional outcomes for older adults diagnosed with COVID-19. Conclusion: High levels of resilience, social support, and exercise, coupled with lower levels of perceived stress and loneliness may serve as protective factors against cognitive and functional decline in older adults who contract COVID-19. Show more

Keywords: Cognition, COVID-19, geriatrics, neuropsychology, Veterans

DOI: 10.3233/ADR-210055

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 115-120, 2022

Authors: Gleerup, Helena Sophia | Simonsen, Anja Hviid | Høgh, Peter

Article Type: Short Communication

Abstract: The added value of neurofilament light chain (NfL) to the existing diagnostic methods is unknown, although a plethora of studies have shown increased levels in cerebrospinal fluid (CSF) and blood in many neurodegenerative and neurological disorders. The added value of CSF NfL was determined in a mixed memory clinic cohort of consecutive patients for 136 patients with Alzheimer’s disease (AD) (n  = 69), mild cognitive impairment (n  = 24), non-AD (n  = 34), and also healthy controls (n  = 9). This study found no increase in the diagnostic accuracy of the etiological diagnoses but knowing the CSF NfL value led to increased diagnostic certainty …for the specialist in neurology. Show more

Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid, dementia, neurofilament light chain

DOI: 10.3233/ADR-210047

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 121-127, 2022

Authors: Rudge, Jonathan D’Arcy

Article Type: Research Article

Abstract: This paper proposes a new hypothesis for Alzheimer’s disease (AD)—the lipid invasion model. It argues that AD results from external influx of free fatty acids (FFAs) and lipid-rich lipoproteins into the brain, following disruption of the blood-brain barrier (BBB). The lipid invasion model explains how the influx of albumin-bound FFAs via a disrupted BBB induces bioenergetic changes and oxidative stress, stimulates microglia-driven neuroinflammation, and causes anterograde amnesia. It also explains how the influx of external lipoproteins, which are much larger and more lipid-rich, especially more cholesterol-rich, than those normally present in the brain, causes endosomal-lysosomal abnormalities and overproduction of the …peptide amyloid-β (Aβ). This leads to the formation of amyloid plaques and neurofibrillary tangles, the most well-known hallmarks of AD. The lipid invasion model argues that a key role of the BBB is protecting the brain from external lipid access. It shows how the BBB can be damaged by excess Aβ, as well as by most other known risk factors for AD, including aging, apolipoprotein E4 (APOE4 ), and lifestyle factors such as hypertension, smoking, obesity, diabetes, chronic sleep deprivation, stress, and head injury. The lipid invasion model gives a new rationale for what we already know about AD, explaining its many associated risk factors and neuropathologies, including some that are less well-accounted for in other explanations of AD. It offers new insights and suggests new ways to prevent, detect, and treat this destructive disease and potentially other neurodegenerative diseases. Show more

Keywords: Alzheimer’s disease, anesthesia, anterograde amnesia, apolipoproteins, blood-brain barrier, cholesterol, ethanol, lipids, lipoproteins, nonesterified fatty acids

DOI: 10.3233/ADR-210299

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 129-161, 2022

Authors: Wrigglesworth, Jo | Harding, Ian H. | Ward, Phillip | Woods, Robyn L. | Storey, Elsdon | Fitzgibbon, Bernadette | Egan, Gary | Murray, Anne | Shah, Raj C. | Trevaks, Ruth E. | Ward, Stephanie | McNeil, John J. | Ryan, Joanne | on behalf of the ASPREE investigator group

Article Type: Research Article

Abstract: Background: There is considerable variability in the rate at which we age biologically, and the brain is particularly susceptible to the effects of aging. Objective: We examined the test-retest reliability of brain age at one- and three-year intervals and identified characteristics that predict the longitudinal change in brain-predicted age difference (brain-PAD, defined by deviations of brain age from chronological age). Methods: T1-weighted magnetic resonance images were acquired at three timepoints from 497 community-dwelling adults (73.8±3.5 years at baseline, 48% were female). Brain age was estimated from whole brain volume, using a publicly available algorithm trained on …an independent dataset. Linear mixed models were used, adjusting for sex, age, and age2 . Results: Excellent retest reliability of brain age was observed over one and three years. We identified a significant sex difference in brain-PAD, where a faster rate of brain aging (worsening in brain age relative to chronological age) was observed in men, and this finding replicated in secondary analyses. The effect size, however, was relatively weak, equivalent to 0.16 years difference per year. A higher score in physical health related quality of life and verbal fluency were associated with a faster rate of brain aging, while depression was linked to a slower rate of brain aging, but these findings were not robust. Conclusion: Our study provides consistent evidence that older men have slightly faster brain atrophy than women. Given the sparsity of longitudinal research on brain age in older populations, future prospective studies are needed to confirm our findings. Show more

Keywords: Aging, biomarkers, cognition, depression, health status, neuroimaging, physical fitness, quality of life, sex, social class

DOI: 10.3233/ADR-220011

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 163-176, 2022

Authors: Moreira, Natália Chermont dos Santos | Lima, Jéssica Ellen Barbosa de Freitas | Marchiori, Marcelo Fiori | Carvalho, Ivone | Sakamoto-Hojo, Elza Tiemi

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a slowly progressive neurodegenerative disease conceptualized as a continuous process, ranging from mild cognitive impairment (MCI), to the mild, moderate, and severe clinical stages of AD dementia. AD is considered a complex multifactorial disease. Currently, the use of cholinesterase inhibitors (ChEI), such as tacrine, donepezil, rivastigmine, and galantamine, has been the main treatment for AD patients. Interestingly, there is evidence that ChEI also promotes neuroprotective effects, bringing some benefits to AD patients. The mechanisms by which the ChEI act have been investigated in AD. ChEI can modulate the PI3K/AKT pathway, which is an important signaling cascade …that is capable of causing a significant functional impact on neurons by activating cell survival pathways to promote neuroprotective effects. However, there is still a huge challenge in the field of neuroprotection, but in the context of unravelling the details of the PI3K/AKT pathway, a new scenario has emerged for the development of more efficient drugs that act on multiple protein targets. Thus, the mechanisms by which ChEI can promote neuroprotective effects and prospects for the development of new drug candidates for the treatment of AD are discussed in this review. Show more

Keywords: Acetylcholinesterase, butyrylcholinesterase, neurodegenerative diseases, neuroprotection, PI3K/AKT pathway

DOI: 10.3233/ADR-210061

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 177-193, 2022

Authors: Cai, Jingwen | Cai, Ming | Xia, Wenwen | Jiang, Lanlan | Song, Hang | Chen, Xiangtao

Article Type: Research Article

Abstract: Background: The number of people with diabetes is increasing, and many patients have significantly impaired cognitive function. For patients with diabetic encephalopathy (DE), simply lowering blood sugar does not improve learning and memory. Studies have shown that β-asarone can significantly improve cognitive impairment in patients with DE, but the specific mechanism of action is unclear. Objective: This experiment hopes to use a variety of experimental methods to clarify the protective effect and mechanism of β-asarone on brain neurons during the development of DE disease. Methods: A high-sugar and high-fat diet and streptozotocin injection-induced DE rat model …was used. β-asarone was administered for four weeks. The experiment used the Morris water maze test, biochemical index detection, and many methods to evaluate the neuroprotective effect of β-asarone on DE rats from various aspects and understand its mechanism. Results: β-asarone reduced neuronal cell damage and significantly improved the learning and memory ability of DE rats. In addition, β-asarone can reduce the oxidative stress response and amyloid-β accumulation in the brain of DE model rats and increase the content of brain-derived neurotrophic factor (BDNF) in the brain tissue, thereby reducing neuronal cell apoptosis and playing a protective role. Conclusion: β-asarone can reduce the accumulation of oxidative stress and amyloid-β in the brain, increase the content of BDNF, reduce the apoptosis of neuronal cells, and exert neuronal protection, thereby improving the learning and memory ability of DE model rats. Show more

Keywords: β-asarone, cognitive dysfunction, diabetic encephalopathy, neuronal cells

DOI: 10.3233/ADR-220001

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 195-206, 2022

Authors: Ho, Gilbert | Choo, Pei Chen | Waragai, Masaaki | Inoue, Satoshi | Masliah, Eliezer | Hashimoto, Makoto

Article Type: Article Commentary

Abstract:  Presuming that Alzheimer’s disease (AD) might represent an antagonistic pleiotropic phenomenon derived from the evolvability of multiple amyloidogenic proteins, targeting such proteins simultaneously could enhance therapeutic efficacy. Furthermore, considering that amyloid-β (Aβ) immunotherapies during reproductive life stage might adversely decrease Aβ evolvability in an offspring’s brain, the disease-modifying Aβ immunotherapies should be limited to post-reproductive time in lifespan. Thus, current Aβ immunotherapy strategies should be revised accordingly. Given that the “adiponectin paradox” might underlie both amyloidosis and cognitive dysfunction in aging brain, blocking activin signaling situated downstream of the adiponectin paradox might be an alternative strategy to prevent AD.

Keywords: Activin, adiponectin paradox, Alzheimer’s disease (AD), amyloid-β immunotherapy, antagonistic pleiotropy, evolvability, follistatin

DOI: 10.3233/ADR-210021

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 207-210, 2022

Authors: Fuller-Thomson, Esme | Nowaczynski, Aliya | MacNeil, Andie

Article Type: Research Article

Abstract: Background: Sensory impairments and cognitive impairment are increasing in scope due to the aging population. Objective: To investigate the association between hearing impairment, vision impairment, and dual sensory impairment with cognitive impairment among older adults. Methods: Secondary analysis of a combination of ten consecutive waves (2008–2017) of the nationally representative American Community Survey. The sample included 5.4 million community-dwelling and institutionalized older adults aged 65 and older. Bivariate and logistic regression models were conducted to examine the association hearing impairment, vision impairment, and dual sensory impairment with cognitive impairment. Results: After controlling for age, …race, education, and income, older adults with only hearing impairment had more than double the odds of cognitive impairment (OR = 2.66, 95% CI = 2.64, 2.68), while older adults with only vision impairment had more than triple the odds of cognitive impairment (OR = 3.63; 95% CI = 3.59, 3.67). For older adults with dual sensory impairment, the odds of cognitive impairment were eight-fold (OR = 8.16; 95% CI = 8.07, 8.25). Similar trends were apparent in each sex and age cohort. Conclusion: Hearing and vision impairment are both independently associated with cognitive impairment. However, dual sensory impairment is associated with substantially higher odds of cognitive impairment, even after controlling for sociodemographic characteristics. Practitioners working with older adults may consider treatment for sensory impairments and cognitive impairment concurrently. Future research is needed to determine if the association is causal, and to investigate the effectiveness of common methods of treatment for sensory impairment for reducing the prevalence of cognitive impairment. Show more

Keywords: Blindness, cognitive dysfunction, deafness, dementia, hearing disorders, hearing loss, vision disorders

DOI: 10.3233/ADR-220005

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 211-222, 2022

Authors: Carrarini, Claudia | De Rosa, Matteo Alessandro | Calisi, Dario | Digiovanni, Anna | Salute, Pierpaolo | Dono, Fedele | Evangelista, Giacomo | Consoli, Stefano | Russo, Mirella | Ferri, Laura | D’Ardes, Damiano | Mattoli, Maria Vittoria | Cipollone, Francesco | Onofrj, Marco | Bonanni, Laura

Article Type: Research Article

Abstract: Background: A 79-year-old woman was admitted to the Neurology Clinic of the University of Chieti-Pescara for a syncope. At admission, the occurrence of an acute stroke was ruled out. Her cognitive status was unimpaired. After three days from the hospitalization, the patient experienced an episode of mixed delirium. Objective: The present case report shows a case of delirium-onset dementia with Lewy bodies (DLB) with a specific electroencephalographic (EEG) pattern from its prodromal stage. Methods: Delirium was assessed by 4AT test. During the hospitalization, the patient underwent a quantitative EEG (QEEG) with spectral analysis. At six months …from the episode of delirium, she was tested by neuropsychological evaluation, QEEG, and 18 F-fluorodeoxyglucose PET/CT to assess the onset of a possible cognitive decline. Results: At baseline, the QEEG exam showed a dominant frequency (DF) in the pre-alpha band (7.5 Hz) with a dominant frequency variability (DFV) of 2 Hz. This pattern is typical of DLB at early stage. After six months, she reported attention deficits in association with cognitive fluctuation and REM sleep behavior disorder. The neurological examination revealed signs of parkinsonism. Cognitive status resulted to be impaired (MoCA = 15/30). QEEG recording confirmed the presence of a DLB-typical pattern (DF = 7.5 Hz, DFV = 2.5 Hz). The 18 F-FDG-PET/CT showed a moderate bilateral posterior hypometabolism (occipital and temporal cortex), with relative sparing of the posterior cingulate cortex compared to cuneus/precuneus (Cingulate Island sign ), and mild bilateral hypometabolism in frontal regions (suggestive of a DLB diagnosis). Conclusion: EEGs may represent supportive and validated biomarkers for delirium-onset prodromal DLB. Show more

Keywords: Delirium, dementia with Lewy bodies, EEG, prodromal dementia

DOI: 10.3233/ADR-220017

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 223-228, 2022

Authors: Zygouris, Stelios | Segkouli, Sofia | Triantafyllidis, Andreas | Giakoumis, Dimitrios | Tsolaki, Magdalini | Votis, Konstantinos | Tzovaras, Dimitrios

Article Type: Short Communication

Abstract: This study conducted a preliminary usability assessment of the Virtual Supermarket Test (VST), a serious game-based self-administered cognitive screening test for mild cognitive impairment (MCI). Twenty-four healthy older adults with subjective cognitive decline and 33 patients with MCI self-administered the VST and then completed the System Usability Scale (SUS). The average SUS score was 83.11 (SD = 14.6). The SUS score was unaffected by age, education, touch device familiarity, and diagnosis of MCI. SUS score correlated with VST performance (r  = –0.496, p  = 0.000). Results of this study indicate good usability of the VST.

Keywords: Age-related memory disorders, cognitive assessment screening instrument, computer games, dementia, mild cognitive impairment, neurocognitive tests, screening, self-evaluation

DOI: 10.3233/ADR-210064

Citation: Journal of Alzheimer's Disease Reports, vol. 6, no. 1, pp. 229-234, 2022