Journal of Alzheimer's Disease - Volume 63, issue 1

Authors: Gerritsen, Adrie A.J. | Bakker, Christian | Verhey, Frans R.J. | Bor, Hans | Pijnenburg, Yolande A.L. | de Vugt, Marjolein E. | Koopmans, Raymond T.C.M.

Article Type: Research Article

Abstract: Background: The progression of dementia in people with young-onset dementia (YOD) is relatively unknown. Objective: To investigate the progression of dementia and cognitive decline in the three most common subtypes in YOD and to explore which factors are associated with this course. Methods: The course of dementia was examined in 198 people with YOD. The primary outcomes were cognitive function, as assessed by the Mini-Mental State Examination (MMSE) and dementia severity, as assessed by the Global Deterioration Scale (GDS). Mixed-model analyses were used to explore factors associated with the course of dementia of the diagnostic sub-types. …Results: The mean overall two-year progression of dementia severity was 0.9 GDS points, this was a statistically significant change (p  = 0.012) and was not significantly different for the three dementia subtypes. The mean overall two-year decline in cognitive function was 1.6 points on the MMSE. The differences in cognitive decline were statistically significant (p  = 0.046) among the three diagnosis groups, AD participants showed the greatest decline, of 2.3 points. In addition to lower education (p  = 0.010), higher scores on the Neuropsychiatric Inventory (NPI) sub-syndromes psychosis (p  < 0.001) and hyperactivity (p  = 0.002) were associated with higher rates of cognitive decline. In contrast, higher scores on the NPI affect cluster were associated with lower levels of cognitive decline (p  < 0.001). Conclusion: Different YOD subtypes show different rates of decline in cognitive functioning, and this decline seems less progressive compared to those observed in studies in late-onset AD. Further research is needed to evaluate whether managing neuropsychiatric symptoms can positively influence the decline of cognitive function. Show more

Keywords: Cognitive decline, progression of dementia, young onset dementia

DOI: 10.3233/JAD-170859

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 343-351, 2018

Authors: Klöppel, Stefan | Kotschi, Maria | Peter, Jessica | Egger, Karl | Hausner, Lucrezia | Frölich, Lutz | Förster, Alex | Heimbach, Bernhard | Normann, Claus | Vach, Werner | Urbach, Horst | Abdulkadir, Ahmed | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Older patients with depression or Alzheimer’s disease (AD) at the stage of early dementia or mild cognitive impairment may present with objective cognitive impairment, although the pathology and thus therapy and prognosis differ substantially. In this study, we assessed the potential of an automated algorithm to categorize a test set of 65 T1-weighted structural magnetic resonance images (MRI). A convenience sample of elderly individuals fulfilling clinical criteria of either AD (n  = 28) or moderate and severe depression (n  = 37) was recruited from different settings to assess the potential of the pattern recognition method to assist in the differential diagnosis of …AD versus depression. We found that our algorithm learned discriminative patterns in the subject’s grey matter distribution reflected by an area under the receiver operator characteristics curve of up to 0.83 (confidence interval ranged from 0.67 to 0.92) and a balanced accuracy of 0.79 for the separation of depression from AD, evaluated by leave-one-out cross validation. The algorithm also identified consistent structural differences in a clinically more relevant scenario where the data used during training were independent from the data used for evaluation and, critically, which included five possible diagnoses (specifically AD, frontotemporal dementia, Lewy body dementia, depression, and healthy aging). While the output was insufficiently accurate to use it directly as a means for classification when multiple classes are possible, the continuous output computed by the machine learning algorithm differed between the two groups that were investigated. The automated analysis thus could complement, but not replace clinical assessments. Show more

Keywords: Alzheimer’s disease, depression, magnetic resonance imaging, supervised machine learning, support vector machine

DOI: 10.3233/JAD-170964

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 353-363, 2018

Authors: Silbert, Lisa C. | Lahna, David | Promjunyakul, Nutta-on | Boespflug, Erin | Ohya, Yusuke | Higashiuesato, Yasushi | Nishihira, Junko | Katsumata, Yuriko | Tokashiki, Takashi | Dodge, Hiroko H.

Article Type: Research Article

Abstract: Background: Cortical gray matter (GM) and white matter (WM) deterioration are signals of neurodegeneration and increased dementia risk; however, their specific etiologies in dementia-free aging is unclear. Objective: The objective of this study was to examine potentially modifiable risk factors of GM and WM degeneration in a well-characterized cohort of dementia-free elderly. Methods: 96 Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging Project (KOCOA) underwent MRI and cognitive evaluation. Serum markers of inflammation (interleukin-6 (IL-6), high sensitivity C-reactive protein), cerebrovascular disease (systolic blood pressure (SBP) 140+, hemoglobin A1C (HgbA1C), total cholesterol), and …essential minerals (copper (Cu), magnesium, and calcium) were examined in relation to mean cortical thickness (MCT) and white matter hyperintensities (WMH), adjusting for age and gender. Voxel-based morphometry (VBM) analyses identified relationships between regional GM density and the above markers. Results: Decreased MCT was associated with SBP 140 + (p  = 0.029) and increased serum IL-6 (p  = 0.036), HgbA1C (p  = 0.002), and Cu (p  = 0.025). In VBM analyses, increased IL-6, HgbA1C, and Cu were associated with decreased GM density in temporal lobe regions. HgbA1C (p  = 0.004) was associated with greater WMH volume. Conclusions: Peripheral markers of Cu, CVD risk, and inflammation are associated with MRI-markers of decreased brain health in dementia-free Okinawan elderly, with regional cortical thinning in areas involved in early accumulation of Alzheimer’s disease pathology. Results identify potentially modifiable biomarkers as targets in the prevention of dementia in older individuals. Show more

Keywords: Aging, Alzheimer’s disease, atrophy, brain, cerebrovascular disorders, cognitive aging, copper, inflammation, magnetic resonance imaging, micronutrients, vascular disease

DOI: 10.3233/JAD-171153

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 365-372, 2018

Authors: Niemantsverdriet, Ellis | Feyen, Bart F.E. | Le Bastard, Nathalie | Martin, Jean-Jacques | Goeman, Johan | De Deyn, Peter Paul | Bjerke, Maria | Engelborghs, Sebastiaan

Article Type: Research Article

Abstract: Background: Differential dementia diagnosis remains a challenge due to overlap of clinical profiles, which often results in diagnostic doubt. Objective: Determine the added diagnostic value of cerebrospinal fluid (CSF) biomarkers for differential dementia diagnosis as compared to autopsy-confirmed diagnosis. Methods: Seventy-one dementia patients with autopsy-confirmed diagnoses were included in this study. All neuropathological diagnoses were established according to standard neuropathological criteria and consisted of Alzheimer’s disease (AD) or other dementias (NONAD). CSF levels of Aβ1 - 42 , T-tau, and P-tau181 were determined and interpreted based on the IWG-2 and NIA-AA criteria, separately. A panel of three …neurologists experienced with dementia made clinical consensus dementia diagnoses. Clinical and CSF biomarker diagnoses were compared to the autopsy-confirmed diagnoses. Results: Forty-two patients (59%) had autopsy-confirmed AD, whereas 29 patients (41%) had autopsy-confirmed NONAD. Of the 24 patients with an ambiguous clinical dementia diagnosis, a correct diagnosis would have been established in 67% of the cases applying CSF biomarkers in the context of the IWG-2 or the NIA-AA criteria respectively. Conclusion: AD CSF biomarkers have an added diagnostic value in differential dementia diagnosis and can help establishing a correct dementia diagnosis in case of ambiguous clinical dementia diagnoses. Show more

Keywords: Ambiguous diagnosis, Alzheimer’s disease, biomarkers, cerebrospinal fluid, dementia, differential dementia diagnosis, neuropathology

DOI: 10.3233/JAD-170927

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 373-381, 2018

Authors: Kristensen, Rachel Underlien | Nørgaard, Ane | Jensen-Dahm, Christina | Gasse, Christiane | Wimberley, Theresa | Waldemar, Gunhild

Article Type: Research Article

Abstract: Background: Polypharmacy (use of ≥5 different medications) and potentially inappropriate medication (PIM) are well-known risk factors for numerous negative health outcomes. However, the use of polypharmacy and PIM in people with dementia is not well-described. Objective: To examine the prevalence of polypharmacy and PIM in older people with and without dementia in a nationwide population. Methods: Cross-sectional study of the Danish population aged ≥65 in 2014 (n  = 1,032,120) based on register data, including information on diagnoses and dispensed prescriptions. Polypharmacy and PIM use among people with (n  = 35,476) and without dementia (n  = 994,231) were compared, stratified …by living situation and adjusted for age, sex, and comorbidity. The red-yellow-green list from the Danish Institute for Rational Pharmacotherapy and the German PRISCUS list were used to define PIM. Results: People with dementia were more frequently exposed to polypharmacy (dementia: 62.6% versus no-dementia: 35.1%, p  < 0.001) and likewise PIM (red-yellow-green: 45.0% versus 29.7%, p  < 0.001; PRISCUS: 24.4% versus 13.2%, p  < 0.001). After adjustments for age, sex, and comorbidity, the likelihood of polypharmacy and PIM was higher for community-dwelling people with dementia than without dementia (odds ratio (OR); [95% confidence interval (CI)] polypharmacy: 1.50 [1.45–1.55]; red-yellow-green: 1.27 [1.23–1.31]; PRISCUS: 1.25 [1.20–1.30]). In contrast, dementia slightly decreased the odds of polypharmacy and PIM in nursing home residents. Conclusion: Use of polypharmacy and PIM were widespread in the older population and more so in people with dementia. This could have negative implications for patient-safety and demonstrates the need for interventions to improve drug therapy in people with dementia. Show more

Keywords: Dementia, inappropriate prescribing, pharmacoepidemiology, polypharmacy, potentially inappropriate medication list

DOI: 10.3233/JAD-170905

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 383-394, 2018

Authors: Kim, Clara Tammy | Myung, Woojae | Lewis, Matthew | Lee, Hyewon | Kim, Satbyul Estella | Lee, Kyungsang | Lee, Chunsoo | Choi, Junbae | Kim, Ho | Carroll, Bernard J. | Kim, Doh Kwan

Article Type: Research Article

Abstract: Background: There is a growing concern that general anesthesia could increase the risk of dementia. However, the relationship between anesthesia and subsequent dementia is still undetermined. Objective: To determine whether the risk of dementia increases after exposure to general anesthesia. Methods: A population-based prospective cohort study analyzing the Korean National Health Insurance Service-National Sample Cohort database was conducted of all persons aged over 50 years (n  = 219,423) from 1 January 2003 and 31 December 2013. Results: 44,956 in the general anesthesia group and 174,469 in the control group were followed for 12 years. The …risk of dementia associated with previous exposure to general anesthesia was increased after adjusting for all covariates such as gender, age, health care visit frequency, and co-morbidities (Hazard ratio = 1.285, 95% confidence interval = 1.262–1.384, time-varying Cox hazard model). In addition, the number of anesthetic agents administered, the number of exposures to general anesthesia, the cumulative exposure time, and the organ category involved in surgery were associated with risk of dementia. Conclusion: In light of the increasing societal burden of dementia, careful surveillance for dementia and prevention guidelines for patients after general anesthesia are needed. Show more

Keywords: Anesthesia, dementia, postoperative complications, risk factor

DOI: 10.3233/JAD-170951

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 395-405, 2018

Article Type: Correction

DOI: 10.3233/JAD-189001

Citation: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 407-407, 2018