Journal of Alzheimer's Disease - Volume 86, issue 2

Authors: Jutten, Roos J. | Thompson, Louisa | Sikkes, Sietske A.M. | Maruff, Paul | Molinuevo, José Luis | Zetterberg, Henrik | Alber, Jessica | Faust, David | Gauthier, Serge | Gold, Michael | Harrison, John | Lee, Athene K.W. | Snyder, Peter J.

Article Type: Review Article

Abstract: The global fight against Alzheimer’s disease (AD) poses unique challenges for the field of neuropsychology. Along with the increased focus on early detection of AD pathophysiology, characterizing the earliest clinical stage of the disease has become a priority. We believe this is an important time for neuropsychology to consider how our approach to the characterization of cognitive impairment can be improved to detect subtle cognitive changes during early-stage AD. The present article aims to provide a critical examination of how we define and measure cognitive status in the context of aging and AD. First, we discuss pitfalls of current methods …for defining cognitive impairment within the context of research shifting to earlier (pre)symptomatic disease stages. Next, we introduce a shift towards a more continuous approach for identifying early markers of cognitive decline and characterizing progression and discuss how this may be facilitated by novel assessment approaches. Finally, we summarize potential implications and challenges of characterizing cognitive status using a continuous approach. Show more

Keywords: Cognitive assessment, early diagnosis, neuropsychology, preclinical Alzheimer’s disease, progression

DOI: 10.3233/JAD-215098

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 511-524, 2022

Authors: Morin, Alexandre | Pressat-Laffouilhere, Thibaut | Sarazin, Marie | Lagarde, Julien | Roue-Jagot, Carole | Olivieri, Pauline | Paquet, Claire | Cognat, Emmanuel | Dumurgier, Julien | Pasquier, Florence | Lebouvier, Thibaut | Ceccaldi, Matthieu | Godefroy, Olivier | Martinaud, Olivier | Grosjean, Julien | Zarea, Aline | Maltête, David | Wallon, David

Article Type: Short Communication

Abstract: This multicenter study was conducted in French memory clinics during the first COVID-2019 lockdown (March–May 2020). The objective was to evaluate the effect of a telemedicine consultation on treatment modification in dementia care. Among 874 patients who had a telemedicine consultation, 103 (10.7%) had treatment modifications, in particular those living with a relative or diagnosed with Alzheimer’s disease. A control group of patients referred March–May 2019 was also included. Treatment modification rate was similar between periods with an adjusted percentage difference of –4% (p  = 0.27). Telemedicine consultations allowed treatment modifications with only a minor short-term negative impact on therapeutic strategies.

Keywords: Alzheimer’s disease, COVID-19, psychoactive drugs, telemedicine, treatments in dementia

DOI: 10.3233/JAD-215459

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 525-530, 2022

Authors: Khan, Noreen | Garcia, Nelda | Mehdipanah, Roshanak | Briceño, Emily M. | Heeringa, Steven G. | Levine, Deborah A. | Gonzales, Xavier F. | Langa, Kenneth M. | Longoria, Ruth | Morgenstern, Lewis B.

Article Type: Short Communication

Abstract: Older adults with significant cognitive impairment require help with activities of daily living. The BASIC-Cognitive Project, set in Nueces County, Texas, is a community-based study examining trends in cognition among Mexican Americans and non-Hispanic Whites. Using cross-sectional data from a cohort study, we found that at least 7% of individuals aged 65 and older with a Montreal Cognitive Assessment (MoCA) score of < 20 (or < 15 for telephone MoCA), did not receive any caregiving help. This conservative estimate highlights an important community need for those with significant cognitive impairment and has implications regarding safety and care for older adults.

Keywords: Activities of daily living, caregiving, dementia, Hispanic, underserved populations

DOI: 10.3233/JAD-215418

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 531-535, 2022

Authors: Yang, Zhiyuan | Sheng, Xiaoning | Qin, Ruomeng | Chen, Haifeng | Shao, Pengfei | Xu, Hengheng | Yao, Weina | Zhao, Hui | Xu, Yun | Bai, Feng

Article Type: Research Article

Abstract: Background: Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer’s disease (AD) spectrum patients. Objective: We recruited 16 amnesic mild cognitive impairment (aMCI) and 6 AD patients in the study. All the patients were stimulated to the left angular gyrus, which was confirmed a strong link to the hippocampus through neuroimaging studies, by the neuro-navigated rTMS for four weeks. Methods: Automated fiber quantification using diffusion tensor imaging metrics and graph theory analysis on functional network were employed to detect the neuroplasticity of brain networks. …Results: After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment score of two groups were significantly improved. Increased FA values of right anterior thalamic radiation among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of thalamic system. Conclusion: We speculated that the rTMS intervention targeting left angular gyrus may be served as a strategy to improve cognitive impairment at the early stage of AD patients, supporting by the neuroplasticity of thalamic system. Show more

Keywords: Alzheimer’s disease, amnesic mild cognitive impairment, neuro-navigated repetitive transcranial magnetic stimulation, thalamic system

DOI: 10.3233/JAD-215390

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 537-551, 2022

Authors: Park, Seon Young | Han, Jiyeon | Kim, Seon Hwa | Suk, Hye Won | Park, Jee Eun | Lee, Dong Young

Article Type: Research Article

Abstract: Background: Air pollution control is necessary to decrease the burden on older adults with cognitive impairment, especially in low- and middle-income countries (LMICs). Objective: This study retrospectively examined the effect of cumulative exposure to air pollution, including NO2 , SO2 , CO, fine particulate matter (PM)10 , PM2.5 , and O3 , on cognitive function in older individuals. Methods: Community-dwelling older adults who underwent the Mini-Mental State Examination (MMSE) from 2007 to 2018 were included in the analyses. We excluded older individuals diagnosed with dementia at baseline, while those who had completed more than two MMSE …tests were included in the longitudinal analyses. Baseline MMSE and changes in MMSE scores were analyzed according to 5-year average concentrations of the district-level air pollutants, after controlling for covariates associated with cognitive decline in older adults. Results: In total, 884,053 (74.3±7.1 years; 64.1% females) and 398,889 (72.3±6.4 years; 67.0% females) older individuals were included in the cross-sectional and longitudinal analyses, respectively. Older individuals exposed to higher levels of NO2 , SO2 , CO, and PM10 showed lower baseline MMSE scores. During follow-up, exposure to higher levels of NO2 , SO2 , CO, and PM10 was associated with greater decreases in MMSE scores in older individuals; for O3 , the opposite pattern was observed. Conclusion: Our findings suggest that exposure to high levels of air pollutants can worsen the cognitive performance of older adults without dementia. Efforts to reduce air pollution in LMICs that have similar levels of pollutants to South Korea are necessary to reduce the burden on older adults with cognitive impairment. Show more

Keywords: Air pollution, cognition, cognitive decline, older adults, South Korea

DOI: 10.3233/JAD-215120

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 553-563, 2022

Authors: Um, Yoo Hyun | Wang, Sheng-Min | Kang, Dong Woo | Kim, Nak-Young | Lim, Hyun Kook

Article Type: Research Article

Abstract: Background: Despite the important associations among sleep, Alzheimer’s disease (AD), subcortical structures, and the cerebellum, structural and functional magnetic resonance imaging (MRI) with regard to these regions and sleep on patients in AD trajectory are scarce. Objective: This study aimed to evaluate the influence of prolonged sleep latency on the structural and functional alterations in the subcortical and cerebellar neural correlates in amyloid-β positive amnestic mild cognitive impairment patients (Aβ+aMCI). Methods: A total of 60 patients with aMCI who were identified as amyloid positive ([18 F] flutemetamol+) were recruited in the study, 24 patients with normal …sleep latency (aMCI-n) and 36 patients prolonged sleep latency (aMCI-p). Cortical thickness and volumes between the two groups were compared. Volumetric analyses were implemented on the brainstem, thalamus, and hippocampus. Subcortical and cerebellar resting state functional connectivity (FC) differences were measured between the both groups through seed-to-voxel analysis. Additionally, group x Aβ interactive effects on FC values were tested with a general linear model. Result: There was a significantly decreased brainstem volume in aMCI-p subjects. We observed a significant reduction of the locus coeruleus (LC) FC with frontal, temporal, insular cortices, hippocampus, and left thalamic FC with occipital cortex. Moreover, the LC FC with occipital cortex and left hippocampal FC with frontal cortex were increased in aMCI-p subjects. In addition, there was a statistically significant group by regional standardized uptake value ratio interactions discovered in cerebro-cerebellar networks. Conclusion: The aforementioned findings suggest that prolonged sleep latency may be a detrimental factor in compromising structural and functional correlates of subcortical structures and the cerebellum, which may accelerate AD pathophysiology. Show more

Keywords: Cerebellum, hippocampus, locus coeruleus, mild cognitive impairment, sleep latency, thalamus

DOI: 10.3233/JAD-215460

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 565-578, 2022

Authors: Benussi, Alberto | Pilotto, Andrea | Cantoni, Valentina | Ferrari, Elisabetta | Borroni, Barbara | Padovani, Alessandro

Article Type: Research Article

Abstract: Background: The neurophysiological correlates of cognitive and motor symptoms in prodromal and overt dementia with Lewy bodies (DLB) are still to be elucidated. Objective: To evaluate if cognitive and motor features of patients with prodromal and overt DLB are associated with the impairment of specific neurotransmitter circuits, evaluated in vivo with transcranial magnetic stimulation (TMS). Methods: Fifty-one patients with DLB (twenty-five prodromal; twenty-six with dementia) underwent neuropsychological and clinical evaluation, with twenty-five patients having at least one follow-up evaluation. All patients were assessed with TMS at baseline, with protocols assessing cholinergic circuits (short latency afferent …inhibition, SAI), GABAergic circuits (short interval intracortical inhibition, SICI), and glutamatergic circuits (intracortical facilitation, ICF). Results: Compared to HC, SICI, ICF, and SAI resulted significantly impaired in both prodromal and overt DLB, with the latter showing a reduced SICI and SAI also compared to prodromal DLB. There was a significant correlation between motor deficits, evaluated with the UPDRS-III, and the impairment of GABAergic (SICI) (r  = 0.729, p  < 0.001) and glutamatergic (ICF) (r –0.608, p  < 0.001) circuits; global cognition, evaluated with the Mini-Mental State Examination, correlated with the impairment of cholinergic (SAI) circuits (r =–0.738, p  < 0.001). Worsening of cognitive functions at follow-up was associated with reduced cholinergic functions at baseline (R2  = 0.53, p  < 0.001). Conclusion: These results suggest that motor and cognitive dysfunctions in prodromal and overt DLB depend on specific and independent neurotransmitter circuits. Show more

Keywords: Cognition, dementia with Lewy bodies, motor, prodromal, short interval intracortical inhibition, transcranial magnetic stimulation

DOI: 10.3233/JAD-215531

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 579-588, 2022

Authors: Engedal, Knut | Gjøra, Linda | Benth, Jūratė Šaltytė | Wagle, Jørgen | Rønqvist, Thale Kinne | Selbæk, Geir

Article Type: Research Article

Abstract: Background: Several studies have found that normative scores on the Montreal Cognitive Assessment Scale (MoCA) vary depending on the person’s education and age. The evidence for different normative scores between sexes is poor. Objective: The main aim of the study was to determine normative scores on the MoCA for Norwegian older adults stratified by educational level, age, and sex. In addition, we aimed to explore sex differences in greater detail. Methods: From two population-based studies in Norway, we included 4,780 people age 70 years and older. People with a diagnosis of dementia or mild cognitive impairment, …a history of stroke, and depression were excluded. Trained health personnel tested the participants with the MoCA. Results: The mean MoCA score varied between 22 and 27 and was highest among women 70–74 years with education >13 years and lowest among men age 85 and older with education ≤10 years. Education, age, and sex were significant predictors of MoCA scores. Conclusion: In the present study of cognitively healthy Norwegian adults 70 years and older, we found that the normative score on the MoCA varied between 22 and 27 depending on a person’s education, age, and sex. We suggest that normative scores should be determined taking these three variables into consideration. Show more

Keywords: Cognition, montreal cognitive assessment, normative scores, older adults, sex differences

DOI: 10.3233/JAD-215442

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 589-599, 2022

Authors: Gao, Lan | Nguyen, Dieu | Moodie, Marj

Article Type: Research Article

Abstract: Background: The established link between cardiovascular disease (CVD) and dementia may provide new insights into dementia prevention. Objective: It aims to quantify the burden of dementia attributable to people with CVD. Methods: A Markov microsimulation model was developed to simulate the lifetime cost and quality-adjusted life-years (QALYs) related to people with and without CVD in Australia. A de-novo systematic review was undertaken to identify all evidence around the association between CVD [i.e., stroke, myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF)] and the risk of developing dementia. Incremental costs and QALY losses were …estimated for people by type of CVD compared to the general Australian population without CVD. Results: Of the comprehensive literature search, 19 observational studies were included in the qualitative synthesis. Patients who had CVD incurred both higher healthcare costs over their lifetime (ranging from $73,131 for patients with AF to $127,396 for patients with HF) and fewer QALYs gains (from –1.099 for patients with MI to –5.163 for patients with stroke), compared to people who did not have CVD. The total incremental economic burden of dementia from patients aged 65 years and over with CVD was $6.45 billion (stroke), $11.89 billion (AF), $17.57 billion (MI), or $7.95 billion (HF) over their remaining life expectancy. Conclusion: The results highlighted the importance of CVD prevention to reduce the CVD burden and decrease the prevalence of dementia. Interventions that target patients with dementia risk factors like CVD may prove to be effective and cost-effective strategies. Show more

Keywords: Burden of disease, cardiovascular disease, dementia, meta-analysis, systematic review

DOI: 10.3233/JAD-215368

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 601-612, 2022

Authors: Tseng, Wen-Yih Isaac | Hsu, Yung-Chin | Kao, Te-Wei

Article Type: Research Article

Abstract: Background: The Clinical Dementia Rating (CDR) has been widely used to assess dementia severity, but it is limited in predicting dementia progression, thus unable to advise preventive measures to those who are at high risk. Objective: Predicted age difference (PAD) was proposed to predict CDR change. Methods: All diffusion magnetic resonance imaging and CDR scores were obtained from the OASIS-3 databank. A brain age model was trained by a machine learning algorithm using the imaging data of 258 cognitively healthy adults. Two diffusion indices, i.e., mean diffusivity and fractional anisotropy, over the whole brain white matter …were extracted to serve as the features for model training. The validated brain age model was applied to a longitudinal cohort of 217 participants who had CDR = 0 (CDR0), 0.5 (CDR0.5), and 1 (CDR1) at baseline. Participants were grouped according to different baseline CDR and their subsequent CDR in approximately 2 years of follow-up. PAD was compared between different groups with multiple comparison correction. Results: PADs were significantly different among participants with different baseline CDRs. PAD in participants with relatively stable CDR0.5 was significantly smaller than PAD in participants who had CDR0.5 at baseline but converted to CDR1 in the follow-up. Similarly, participants with relatively stable CDR0 had significantly smaller PAD than those who were CDR0 at baseline but converted to CDR0.5 in the follow-up. Conclusion: Our results imply that PAD might be a potential imaging biomarker for predicting CDR outcomes in patients with CDR0 or CDR0.5. Show more

Keywords: Brain age, dementia, diffusion MRI, predicted age difference

DOI: 10.3233/JAD-215380

Citation: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 613-627, 2022