Journal of Alzheimer's Disease - Volume 97, issue 2

Authors: Nguyen, Sarah A. | Oughli, Hanadi Ajam | Lavretsky, Helen

Article Type: Review Article

Abstract: Integrative medicine takes a holistic approach because it considers multiple aspects of the individual. This includes a person’s physical, emotional, interpersonal, behavioral, nutritional, environmental, and spiritual dimensions of wellbeing that contribute to the Whole Person Health. There is increasing interest and popularity of integrative approaches to treating cognitive decline and dementia because of the multifactorial nature of aging and the limited pharmacological interventions available in treating cognitive decline and dementia, particularly Alzheimer’s disease, the most common type of dementia. This review summarizes the existing evidence using complementary and integrative medicine therapies in cognitive decline and Alzheimer’s disease. This includes the …use of mind-body therapies, lifestyle interventions (nutritional, physical exercise, stress reduction), and other integrative modalities. Unfortunately, there are still limited studies available to guide clinicians despite the increasing popularity of integrative treatments. Show more

Keywords: Alternative, Alzheimer’s disease, complementary, dementia, integrative, neurocognitive disorders

DOI: 10.3233/JAD-230710

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 523-540, 2024

Authors: Toh, Keith Z.X. | Koh, Ming Yi | Loh, Enver D.W. | Sia, Ching-Hui | Chong, Yaofeng | Yeo, Leonard L.L. | Sharma, Vijay K. | Lim, Mervyn J.R. | Tan, Benjamin Y.Q.

Article Type: Systematic Review

Abstract: Background: Cognitive impairment, and in the long term Alzheimer’s disease, vascular, or mixed dementia, are potential complications of moyamoya disease (MMD), of which the prevalence and associations are not well established. Objective: We performed a systematic review and meta-analysis to investigate the prevalence of cognitive impairment in adult patients with MMD as well as its clinical and demographic correlates. Methods: We performed a systematic search of four electronic databases: PubMed (MEDLINE), EMBASE, Scopus, and Cochrane Library, profiling studies from inception until 7 May 2023. Clinical data consisting of population characteristics, comorbidities, cognitive assessment tools used, and …prevalence of cognitive impairment was extracted. Results: Seventeen studies were included in the meta-analysis, with a total study population of 1,190 patients. All studies assessed cognition, and the overall prevalence of cognitive impairment in MMD patients was 54.59%. A subgroup analysis identified that the prevalence of executive dysfunction in MMD patients was 31.55%. We performed a meta-regression analysis which identified that cognitive impairment was not associated with age, education level, or a history of ischemic or hemorrhagic stroke. Conclusions: A substantial proportion of MMD patients have cognitive impairment, and cognitive impairment was found to have no association with a history of stroke. Further research is necessary to investigate the longitudinal relationship of MMD and cognitive impairment, and the impact of bypass surgery on cognitive impairment. Show more

Keywords: Alzheimer’s disease, cognitive impairment, moyamoya disease, prevalence

DOI: 10.3233/JAD-230979

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 541-552, 2024

Authors: Keizer, Hiskias G. | Brands, Ruud | Oosting, Ronald S. | Seinen, Willem

Article Type: Research Article

Abstract: Despite decades of intense research, the precise etiology of Alzheimer’s disease (AD) remains unclear. In this hypothesis, we present a new perspective on this matter by identifying carnitine palmitoyl transferase-2 (CPT2) as a central target in AD. CPT2 is an enzyme situated within the inner mitochondrial membrane, playing a crucial role in beta-oxidation of fatty acids. It exhibits high sensitivity to hydrogen peroxide. This sensitivity holds relevance for the etiology of AD, as all major risk factors for the disease share a commonality in producing an excess of hydrogen peroxide right at this very mitochondrial membrane. We will explain the …high sensitivity of CPT2 to hydrogen peroxide and elucidate how the resulting inhibition of CPT2 can lead to the characteristic phenotype of AD, thus clarifying its central role in the disease’s etiology. This insight holds promise for the development of therapies for AD which can be implemented immediately. Show more

Keywords: Alzheimer’s disease, AMP-kinase pathway dependent integrated stress response, carnitine palmitoyl transferase 2, CPT2, hydrogen peroxide, hypoxia, longevity, radical oxygen species

DOI: 10.3233/JAD-230991

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 553-558, 2024

Authors: Dosso, Jill A. | Kailley, Jaya N. | Robillard, Julie M.

Article Type: Short Communication

Abstract: The quality of information about dementia retrieved using ChatGPT is unknown. Content was evaluated for length, readability, and quality using the QUEST, a validated tool, and compared against online material from three North American organizations. Both sources of information avoided conflicts of interest, supported the patient-physician relationship, and used a balanced tone. Official bodies but not ChatGPT referenced identifiable research and pointed to local resources. Users of ChatGPT are likely to encounter accurate but shallow information about dementia. Recommendations are made for information creators and providers who counsel patients around digital health practices.

Keywords: Alzheimer’s disease, artificial intelligence, dementia, health

DOI: 10.3233/JAD-230573

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 559-565, 2024

Authors: Digma, Leonardino A. | Winer, Joseph R. | Greicius, Michael D.

Article Type: Article Commentary

Abstract: With the FDA approval of aducanumab and lecanemab, and with the recent statistically significant phase 3 clinical trial for donanemab, there is growing enthusiasm for anti-amyloid antibodies in the treatment of Alzheimer’s disease. Here, we discuss three substantial limitations regarding recent anti-amyloid clinical trials: 1) there is little evidence that amyloid reduction correlates with clinical outcome, 2) the reported efficacy of anti-amyloid therapies may be explained by functional unblinding, and 3) donanemab had no effect on tau burden in its phase 3 trial. Taken together, these observations call into question the efficacy of anti-amyloid therapies.

Keywords: Alzheimer’s disease, amyloid, clinical trials, tau

DOI: 10.3233/JAD-231198

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 567-572, 2024

Authors: Maters, Jasper | van der Steen, Jenny T. | de Vugt, Marjolein E. | Bakker, Christian | Koopmans, Raymond T.C.M.

Article Type: Research Article

Abstract: Background: The evidence underpinning palliative care in dementia is mostly based on research in older populations. Little is known about the palliative care needs of people with young-onset dementia (YOD). Objective: To describe palliative care practices including advance care planning (ACP) in people with YOD residing in Dutch nursing homes. Methods: The study presents baseline questionnaire data from an observational cohort study. Physicians, family caregivers, and nursing staff completed questionnaires about 185 residents with YOD. The questionnaires included items on sociodemographics, quality of life measured with the quality of life in late-stage dementia (QUALID) scale, dementia-related …somatic health problems, symptoms, pain medication, psychotropic drugs, and ACP. Results: The mean age was 63.9 (SD 5.8) years. Half (50.3%) of them were female. Alzheimer’s disease dementia (42.2%) was the most prevalent subtype. The mean QUALID score was 24.0 (SD 7.9) as assessed by family caregivers, and 25.3 (SD 8.6) as assessed by the nursing staff. Swallowing problems were the most prevalent dementia-related health problem (11.4%). Agitation was often reported by physicians (42.0%) and nursing staff (40.5%). Psychotropics were prescribed frequently (72.3%). A minority had written advance directives (5.4%) or documentation on treatment preferences by the former general practitioner (27.2%). Global care goals most often focused on comfort (73.9%). Proportions of do-not-treat orders were higher than do-treat orders for all interventions except for hospitalization and antibiotics. Conclusions: ACP must be initiated earlier, before nursing home admission. A palliative approach seems appropriate even though residents are relatively young and experience few dementia-related health problems. Show more

Keywords: Advance care planning, Alzheimer’s disease, palliative care, young-onset dementia

DOI: 10.3233/JAD-230486

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 573-586, 2024

Authors: Almkvist, Ove | Larsson, Maria | Graff, Caroline

Article Type: Research Article

Abstract: Background: Impaired odor identification is a characteristic of sporadic Alzheimer’sdisease(AD), but its presence in autosomal-dominantAD (adAD) remains uncertain. Objective: To investigate odor identification ability in mutation carriers (MC) and non-carriers (NC) of adAD in relation to years to estimated clinical onset clinical onset (YECO) of disease. Methods: Participants from six families with autosomal-dominant mutations (APP Swedish, APP Arctic, and PSEN1 mutations) included 20 MC and 20 NC. The groups were comparable in age, gender, education, number of APOE ɛ4 alleles, and YECO, but differed in global cognition (Mini-Mental State …Examination). The MC group included individuals in asymptomatic, symptomatic cognitively unimpaired, mild cognitive impairment, and dementia stages of disease, spanning approximately 40 years of the AD continuum. All NC were asymptomatic. Olfactory function was assessed by means of free and cued identification of common odors summarized as total identification. Results: MC performed poorer than NC in free and total identification. Four MC and none of the NC were anosmic. Olfactory functions in MC and NC were significantly and inversely related to time course (YECO) for both free and total identification. The decline in free identification began approximately 10 years prior to the estimated clinical onset of AD in MC. Odor identification proficiency was associated with episodic memory and executive function in MC and NC. Conclusions: Impaired odor identification is present well before the clinical diagnosis of AD in MC and is associated with disease progression. Odor identification ability may be a useful early biomarker for adAD. Show more

Keywords: Alzheimer’s disease, autosomal-dominant Alzheimer’s disease, cognition, mutation carriers, non-carriers, odor identification

DOI: 10.3233/JAD-230618

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 587-598, 2024

Authors: Ricci, Francesco | Martorana, Alessandro | Bonomi, Chiara G. | Serafini, Chiara | Mercuri, Nicola B. | Koch, Giacomo | Motta, Caterina

Article Type: Research Article

Abstract: Background: Blood-brain barrier (BBB) dysfunction could favor the pathogenesis and progression of Alzheimer’s disease (AD). Vascular risk factors (VRF) could worsen BBB integrity, thus promoting neurode generation. Objective: To investigate BBB permeability and its relation with VRF along the AD continuum (ADc). Cerebrospinal fluid (CSF) Amyloid (A) and p-tau (T) levels were used to stratify patients. Methods: We compared CSF/plasma albumin ratio (QAlb) of 131 AD patients and 24 healthy controls (HC). APOE genotype and VRF were evaluated for each patient. Spearman’s Rho correlation was used to investigate the associations between Qalb …and CSF AD biomarkers. Multivariate regression analyses were conducted to explore the relationship between Qalb and AD biomarkers, sex, age, cognitive status, and VRF. Results: QAlb levels did not show significant difference between ADc patients and HC (p  = 0.984). However, QAlb was significantly higher in A  + T–compared to A  + T+ (p  = 0.021). In ADc, CSF p-tau demonstrated an inverse correlation with QAlb, a finding confirmed in APOE4 carriers (p  = 0.002), but not in APOE3 . Furthermore, in APOE4 carriers, sex, hypertension, and hypercholesterolemia were associated with QAlb (p  = 0.004, p  = 0.038, p  = 0.038, respectively), whereas only sex showed an association in APOE3 carriers (p  = 0.026). Conclusions: BBB integrity is preserved in ADc. Among AT categories, A  + T–have a more permeable BBB than A  + T+. In APOE4 carriers, CSF p-tau levels display an inverse association with BBB permeability, which in turn, seems to be affected by VRF. These data suggest a possible relationship between BBB efficiency, VRF and CSF p-tau levels depending on APOE genotype. Show more

Keywords: Alzheimer’s disease, Alzheimer’s disease continuum, APOE, biomarkers, blood-brain barrier, QAlb, vascular risk factors

DOI: 10.3233/JAD-230792

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 599-607, 2024

Authors: Ren, Jiawen | Yu, Yongquan | Wang, Yucheng | Dong, Yu | Shen, Xiaobing

Article Type: Research Article

Abstract: Background: Glyphosate is the most commonly used herbicide with potential neurotoxicity. However, limited epidemical evidence is found in the relationship between glyphosate and cognitive impairment, especially in the cognitive-disrupting sensitive elderly populations. Objective: This study aimed to examine the association of urinary glyphosate exposure with cognitive impairment in the United State (US) older adults. Methods: Cognitive impairment was determined by the following four tests: the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) Immediate Recall test (IR), the CERAD Delayed Recall tests (DR), the Animal Fluency (AF) test and the Digit Substitution test (DSST). Survey …weighted logistic regression and restricted cubic splines were applied to evaluate and visualize the association between glyphosate and cognitive impairment. Results: A total of 465 elderly adults were identified in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 cycle, and among them, 83.87% individuals had detectable urinary levels of glyphosate (0.628 ng/mL in average). After adjusting for the potential covariates, glyphosate was significantly linked to increased DR and AF impairment, and the corresponding ORs were 1.52 (1.01 to 2.30, p  = 0.049) and 1.69 (1.11 to 2.59, p  = 0.019), respectively. No significant association was identified between glyphosate and IR or DSST impairment. The RCS plot further confirmed the linear and positive relationships between glyphosate and DR and AF impairment. Conclusions: These findings suggested that exposure to glyphosate might be associated with declined cognitive function in the elderly, and it might be prudent to evaluate cognitive outcomes for aged individuals with glyphosate exposures. Show more

Keywords: Alzheimer’s disease, cognitive impairment, glyphosate, logistic regression, restricted cubic spline

DOI: 10.3233/JAD-230782

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 609-620, 2024

Authors: Rehman, Habbiburr | Ang, Ting Fang Alvin | Tao, Qiushan | Espenilla, Arielle Lauren | Au, Rhoda | Farrer, Lindsay A. | Zhang, Xiaoling | Qiu, Wei Qiao

Article Type: Research Article

Abstract: Background: Although cerebrospinal fluid (CSF) amyloid-β42 peptide (Aβ42 ) and phosphorylated tau (p-tau) and blood p-tau are valuable for differential diagnosis of Alzheimer’s disease (AD) from cognitively normal (CN) there is a lack of validated biomarkers for mild cognitive impairment (MCI). Objective: This study sought to determine how plasma and CSF protein markers compared in the characterization of MCI and AD status. Methods: This cohort study included Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants who had baseline levels of 75 proteins measured commonly in plasma and CSF (257 total, 46 CN, 143 MCI, and 68 AD). …Logistic regression, least absolute shrinkage and selection operator (LASSO) and Random Forest (RF) methods were used to identify the protein candidates for the disease classification. Results: We observed that six plasma proteins panel (APOE, AMBP, C3, IL16, IGFBP2, APOD) outperformed the seven CSF proteins panel (VEGFA, HGF, PRL, FABP3, FGF4, CD40, RETN) as well as AD markers (CSF p-tau and Aβ42 ) to distinguish the MCI from AD [area under the curve (AUC) = 0.75 (plasma proteins), AUC = 0.60 (CSF proteins) and AUC = 0.56 (CSF p-tau and Aβ42 )]. Also, these six plasma proteins performed better than the CSF proteins and were in line with CSF p-tau and Aβ42 in differentiating CN versus MCI subjects [AUC = 0.89 (plasma proteins), AUC = 0.85 (CSF proteins) and AUC = 0.89 (CSF p-tau and Aβ42 )]. These results were adjusted for age, sex, education, and APOE ϵ 4 genotype. Conclusions: This study suggests that the combination of 6 plasma proteins can serve as an effective marker for differentiating MCI from AD and CN. Show more

Keywords: Alzheimer’s disease, biomarkers, mild cognitive impairment, proteins

DOI: 10.3233/JAD-230837

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 621-633, 2024