Journal of Alzheimer's Disease - Volume 75, issue 2

Authors: Alsharif, Alaa A. | Wei, Li | Ma, Tiantian | Man, Kenneth K.C. | Lau, Wallis C.Y. | Brauer, Ruth | Almetwazi, Mansour | Howard, Rob | Wong, Ian C.K.

Article Type: Research Article

Abstract: Background: Few studies have shown that an increased risk of dementia is associated with diabetes mellitus. Objective: To estimate the prevalence and incidence of dementia in people with diabetes in primary care in the UK. Methods: We conducted a descriptive study using the UK The Health Improvement Network (THIN) database. People diagnosed with diabetes from 2000 to 2016 were included in the study. Prevalence and incidence rates of dementia were calculated annually, stratified by age and gender. Results: The prevalence of dementia was 0.424% [95% CI (0.420%–0.427%)] in 2000 and 2.508% [95% CI (2.501%–2.515%)] …in 2016. The highest prevalence was in those aged 85+ from 2.9% [95% CI (2.890%–2.974%)] in 2000 to 11.3% [95% CI (11.285%–11.384%)] in 2016. The incidence of dementia increased 3.7 times, from 0.181 cases per 100 persons [95% CI (0.179–0.183)] in 2000 to 0.683 cases per 100 persons [95% CI (0.679–0.686)] in 2016, respectively. Women had a higher prevalence and incidence of dementia than men 3.138% [95% CI (3.127%–3.150%)] versus 2.014% [95% CI (2.006%–2.022%)] and 0.820 [95% CI (0.814–0.826)] versus 0.576 cases per 100 persons [95% CI (0.571–0.580)] in 2016, respectively. Conclusion: There was a trend of increasing prevalence and incidence of dementia in people with diabetes over the period of 2000 to 2016. This study adds to the evidence on dementia prevalence and incidence, particularly in the diabetic population. Show more

Keywords: Dementia, diabetes mellitus, epidemiology, incidence, prevalence, THIN database

DOI: 10.3233/JAD-191115

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 607-615, 2020

Authors: Thomas, Binu P. | Tarumi, Takashi | Sheng, Min | Tseng, Benjamin | Womack, Kyle B. | Cullum, C. Munro | Rypma, Bart | Zhang, Rong | Lu, Hanzhang

Article Type: Research Article

Abstract: Aerobic exercise (AE) has recently received increasing attention in the prevention of Alzheimer’s disease (AD). There is some evidence that it can improve neurocognitive function in elderly individuals. However, the mechanism of these improvements is not completely understood. In this prospective clinical trial, thirty amnestic mild cognitive impairment participants were enrolled into two groups and underwent 12 months of intervention. One group (n  = 15) performed AE training (8M/7F, age = 66.4 years), whereas the other (n  = 15) performed stretch training (8M/7F, age = 66.1 years) as a control intervention. Both groups performed 25–30 minutes training, 3 times per week. Frequency and duration were gradually …increased over time. Twelve-month AE training improved cardiorespiratory fitness (p  = 0.04) and memory function (p  = 0.004). Cerebral blood flow (CBF) was measured at pre- and post-training using pseudo-continuous-arterial-spin-labeling MRI. Relative to the stretch group, the AE group displayed a training-related increase in CBF in the anterior cingulate cortex (p  = 0.016). Furthermore, across individuals, the extent of memory improvement was associated with CBF increases in anterior cingulate cortex and adjacent prefrontal cortex (voxel-wise p  < 0.05). In contrast, AE resulted in a decrease in CBF of the posterior cingulate cortex, when compared to the stretch group (p  = 0.01). These results suggest that salutary effects of AE in AD may be mediated by redistribution of blood flow and neural activity in AD-sensitive regions of brain. Show more

Keywords: Aerobic exercise training, Alzheimer’s disease, amnestic mild cognitive impairment, anterior cingulate cortex, cerebral blood flow, posterior cingulate cortex, stretch training

DOI: 10.3233/JAD-190977

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 617-631, 2020

Authors: Pagen, Linda H.G. | van de Ven, Vincent G. | Gronenschild, Ed H.B.M. | Priovoulos, Nikos | Verhey, Frans R.J. | Jacobs, Heidi I.L.

Article Type: Research Article

Abstract: Background: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer’s disease (AD) patients. Objective: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance. Methods: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the …cerebellar DMN seeds and the cerebral DMN. Results: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients. Conclusion: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases. Show more

Keywords: Alzheimer’s disease, cerebellum, functional connectivity, resting state functional MRI

DOI: 10.3233/JAD-191127

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 633-647, 2020

Authors: Clark, Lindsay R. | Zuelsdorff, Megan | Norton, Derek | Johnson, Sterling C. | Wyman, Mary F. | Hancock, Laura M. | Carlsson, Cynthia M. | Asthana, Sanjay | Flowers-Benton, Susan | Gleason, Carey E. | Johnson, Heather M.

Article Type: Research Article

Abstract: Background: Midlife cardiovascular risk factors increase risk for Alzheimer’s disease (AD). Despite disproportionately high cardiovascular disease and dementia rates, African Americans are under-represented in studies of AD risk and research-based guidance on targeting vascular risk factors is lacking. Objective: This study investigated relationships between specific cardiovascular risk factors and cerebral perfusion in White and African American adults enriched for AD risk. Methods: Participants included 397 cognitively unimpaired White (n  = 330) and African American (n  = 67) adults enrolled in the Wisconsin Alzheimer’s Disease Research Center who underwent pseudo-continuous arterial spin labeling MRI. Multiple linear regression models examined …independent relationships between cardiovascular risk factors and mean cerebral perfusion. Subsequent interaction and stratified models assessed the role for APOE genotype and race. Results: When risk factor p -values were FDR-adjusted, diastolic blood pressure was significantly associated with mean perfusion. Tobacco use, triglycerides, waist-to-hip ratio, and a composite risk score were not associated with perfusion. Without FDR adjustment, a relationship was also observed between perfusion and obesity, cholesterol, and fasting glucose. Neither APOE genotype nor race moderated relationships between risk factors and perfusion. Conclusion: Higher diastolic blood pressure predicted lower perfusion more strongly than other cardiovascular risk factors. This relationship did not vary by racial group or genetic risk for AD, although the African American sample had greater vascular risk burden and lower perfusion rates. Our findings highlight the need to prioritize inclusion of underrepresented groups in neuroimaging studies and to continue exploring the link between modifiable risk factors, cerebrovascular health, and AD risk in underrepresented populations. Show more

Keywords: Aging, Alzheimer’s disease, blood pressure, cerebrovascular circulation, neuroimaging, obesity

DOI: 10.3233/JAD-190360

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 649-660, 2020

Authors: Vismara, Matteo | Cirnigliaro, Giovanna | Piccoli, Eleonora | Giorgetti, Federica | Molteni, Laura | Cremaschi, Laura | Fumagalli, Giorgio G. | D’addario, Claudio | Dell’Osso, Bernardo

Article Type: Research Article

Abstract: Frontotemporal dementia (FTD) includes a group of neurocognitive syndromes, clinically characterized by altered behaviors, impairment of language proficiency, and altered executive functioning. FTD is one of the most frequently observed forms of dementia in the elderly population and the most common in presenile age. As for other subtypes of dementia, FTD incidence is constantly on the rise due to the steadily increasing age of the population, and its recognition is now becoming a determinant for clinicians. FTD and psychiatric disorders can overlap in terms of clinical presentations by sharing a common genetic predisposition and neuropathological mechanism in some cases. Nonetheless, …this association is often unclear and underestimated. Since its first reports, research into FTD has constantly grown, with the identification of recent findings related to its neuropathology, genetic, clinical, and therapeutic issues. Literature is thriving on this topic, with numerous research articles published in recent years. In the present review, we aimed to provide an updated description of the clinical manifestations that link and potentially confound the diagnosis of FTD and psychiatric disorders in order to improve their differential diagnosis and early detection. In particular, we systematically reviewed the literature, considering articles specifically focused on the behavioral variant FTD, published after 2015 on the PubMed database. Show more

Keywords: Behavioral symptoms, bipolar disorder, differential diagnosis, frontotemporal lobar degeneration, frontotemporal lobe dementia, genetics, neuroimaging, psychiatric disorders, schizophrenia

DOI: 10.3233/JAD-191333

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 661-673, 2020

Authors: Maltby, John | Chan, Mahathir | Anderson, David | Mukaetova-Ladinska, Elizabeta B.

Article Type: Research Article

Abstract: Background: The Salzburg Dementia Test Prediction (SDTP), developed using artificial intelligence and based on the Mini-Mental State Examination (MMSE), was recently introduced as a brief cognitive screening tool for cognitive impairment. Objective: In the current study, we investigated whether the STDP can be used as a valid bed-side cognitive screening tool for dementia patients, in an English-speaking, medical inpatient setting. Methods: 216 medically ill older patients who had completed the MMSE (from which the SDTP scores can be calculated), with a subsample 58 patients who had also completed the ACE-R/ACE-III scales. Diagnosis of one of four …dementia types (n  = 127) and socio-demographic information were also collected. MMSE, SDTP, ACE-R/ACE-III, and dementia diagnosis were used to examine the construct validity of the SDTP through assessments of the structural, concurrent, and convergent validity. Results: The SDTP shows structural validity through demonstrating uni-dimensionality. Construct validity was demonstrated by sufficient correlation sizes with MMSE scores against a benchmark correlation size for most of the subsample, except vascular dementia. Convergent validity was demonstrated for the STDP with equivalent correlations sizes with ACE-R/ACE-III as the MMSE across all samples, though for vascular dementia the magnitude of this correlation was not as strong. Conclusions: Our findings support using STDP as a brief assessment tool among patients who have been diagnosed with Alzheimer’s disease, Lewy body disease, and mixed dementia; however, there is some statistical variability to overall MMSE scores and correlations with the ACE-R/ACE-III among patients diagnosed with vascular dementia. Show more

Keywords: Cognitive test, dementia, medically ill, Mini-Mental State Examination, older people, Salzburg Dementia Test Prediction

DOI: 10.3233/JAD-200183

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 675-681, 2020

Article Type: Correction

DOI: 10.3233/JAD-209003

Citation: Journal of Alzheimer's Disease, vol. 75, no. 2, pp. 683-683, 2020