%0 Journal Article %J J Alzheimers Dis %D 2020 %T Specific Neuropsychiatric Symptoms Are Associated with Faster Progression in Alzheimer's Disease: Results of the Prospective Dementia Registry (PRODEM-Austria). %A Defrancesco, Michaela %A Marksteiner, Josef %A Kemmler, Georg %A Dal-Bianco, Peter %A Ransmayr, Gerhard %A Benke, Thomas %A Mosbacher, Jochen %A Höller, Yvonne %A Schmidt, Reinhold %X

BACKGROUND: Neuropsychiatric symptoms (NPS) occur frequently in the course of Alzheimer's disease (AD) and are suspected to be associated with a faster dementia progression. Numerous reports have defined specific subsyndromes, summarized in clusters of items of the Neuropsychiatric Inventory (NPI).

OBJECTIVE: This study investigated the influence of specific NPI subsyndromes and clinical patient characteristics on dementia progression.

METHODS: Data of the prospective registry on dementia in Austria (PRODEM) were retrospectively analyzed. Cognitive functioning was determined at baseline and 2 yearly follow-up visits using the Mini-Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's dementia neuropsychological test battery (CERAD). To assess NPS, the NPI was used: NPI items were classified in three subsyndromes (psychotic cluster, behavioral cluster, emotional cluster).

RESULTS: Out of the 662 included patients (mean age 76.4±8.4 years), 43% completed follow-up visits for two years. Significant correlation between higher scores in all three subsyndromes and worse cognitive performance were found for MMSE score, naming, and verbal fluency. Results of linear mixed model analysis revealed lower age and higher scores in the psychotic cluster as significant predictors of changes in MMSE with time.

CONCLUSION: In this study, we report the influence of psychotic subsyndromes and lower age on faster MMSE decline in early AD. These results emphasize the importance of not only assessing but also differentiating neuropsychiatric symptoms in subsyndromes in the early stages of AD as a possible predictor of disease progression.

%B J Alzheimers Dis %V 73 %P 125-133 %8 2020 Jan 07 %G eng %N 1 %R 10.3233/JAD-190662 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Caregiving and Caregiver Burden in Dementia Home Care: Results from the Prospective Dementia Registry (PRODEM) of the Austrian Alzheimer Society. %A Ransmayr, Gerhard %A Hermann, Philipp %A Sallinger, Katharina %A Benke, Thomas %A Seiler, Stephan %A Dal-Bianco, Peter %A Marksteiner, Josef %A Defrancesco, Michaela %A Sanin, Günter %A Struhal, Walter %A Guger, Michael %A Vosko, Milan %A Hagenauer, Karin %A Lehner, Riccarda %A Futschik, Andreas %A Schmidt, Reinhold %X

BACKGROUND: Comprehensive studies on caregiver burden (CB) of persons caring for dementia patients differ methodologically and show variable results.

OBJECTIVE: Analysis of known and hypothesized factors of CB in home care of dementia patients.

METHODS: Multicenter longitudinal study comprising 585 persons caring mostly for Alzheimer's disease patients (age median 77.25 years, Mini-Mental State Examination raw score median 23) using the Zarit Caregiver Burden Interview (CBI). Known patient-related determinants of CB were studied, such as dementia severity (Clinical Dementia Rating, CDR), neuropsychological deficits (CERAD-Plus), neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI), disability (Disability Assessment for Dementia, DAD), dependency (Dependency Scale, DS), and moreover, unclarified potential factors (age, sex, education of patients; age, sex, occupational status of the caregivers; family relationship). Psychological and somatic effects of CB were analyzed (factor analysis).

RESULTS: Caregiver age was median 61. Female caregivers prevailed (67.8%). Median CBI sum score (CBIss) was 16 at baseline. After two years, CBIss was 22 and 37% of the caregivers reported mild to moderate (CBIss 21-40), 16.8% moderate to severe or severe (≥41), and 46.2% absent to little CB (CBIss ≤ 20). CB correlated positively with NPI, CDR, DS scores, disability (DAD), years of education of the patients, and proximity of patient and caregiver sex (female), and negatively with caregiver age. Caregivers reported restrictions of time, health problems, and negative emotions.

CONCLUSION: The findings are applicable to identify persons at risk for substantial CB and its consequences. There is demand for personal, psychological, and medical support of caregivers and increasing male participation.

%B J Alzheimers Dis %V 63 %P 103-114 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29614643?dopt=Abstract %R 10.3233/JAD-170657 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Severity of Depression Impacts Imminent Conversion from Mild Cognitive Impairment to Alzheimer's Disease. %A Defrancesco, Michaela %A Marksteiner, Josef %A Kemmler, Georg %A Fleischhacker, Walter Wolfgang %A Blasko, Imrich %A Deisenhammer, Eberhard A %X

BACKGROUND: Mild cognitive impairment (MCI) has been suggested to represent a prodromal stage of dementia and to confer a high risk for conversion to dementia Alzheimer's type (DAT).

OBJECTIVES: In this study, we examined the predictive value of depressive symptoms and neuropsychological variables on conversion of MCI to DAT.

METHODS: Neuropsychological and clinical follow-up data of 260 MCI patients seen at the Psychiatric Memory Clinic of the Medical University of Innsbruck between 2005 and 2015 were analyzed retrospectively. Depression was assessed using the Geriatric Depression Scale (GDS). Potential predictors of conversion from MCI to DAT were analyzed by logistic regression analyses and additional survival-analytic methods.

RESULTS: Of the 260 patients (mean age 71.5±7.7 years), 83 (32%) converted to DAT within a mean follow-up time of 3.2±2.2 years and estimated one-year conversion rate of 10.1%. The univariate analysis showed with few exceptions (gender, use of antidepressants, low GDS score) group differences at baseline in patients converted to DAT compared to stable MCI patients. Logistic regression analysis as well as survival analysis revealed moderate to severe depression together with higher age and specific cognitive deficits as predictors of conversion from MCI to DAT.

CONCLUSION: Our results support the predictive value of different neuropsychological measures on the progression of DAT. In addition, we found a strong negative influence of depression on conversion to DAT in MCI patients. These results emphasize the importance of assessing depressive symptoms in the early stages of DAT when evaluating the conversion from MCI to DAT.

%B J Alzheimers Dis %V 59 %P 1439-1448 %G eng %N 4 %R 10.3233/JAD-161135 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Targeted Metabolomic Analysis of Soluble Lysates from Platelets of Patients with Mild Cognitive Impairment and Alzheimer's Disease Compared to Healthy Controls: Is PC aeC40:4 a Promising Diagnostic Tool? %A Oberacher, Herbert %A Arnhard, Kathrin %A Linhart, Caroline %A Diwo, Angela %A Marksteiner, Josef %A Humpel, Christian %X

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system. The use of biological fluids in AD diagnosis remains limited to the analysis of specific protein biomarkers in cerebrospinal fluid. However, metabolomic analysis has recently revealed several metabolites in plasma, especially phosphatidylcholines (PC), as putative biomarkers specific for AD. Following on previous reports of platelet abnormalities in AD, we hypothesized that platelets metabolites released in plasma may offer new biomarkers in AD. The aim of the present study was to apply targeted metabolomics to compare metabolites in soluble lysates of platelets from healthy controls (CO), patients with mild cognitive impairment (MCI), and patients with AD in a cohort of 90 subjects. We could target 163 metabolites and quantitative data were obtained for 91 metabolites. Among these, the lipid PC aeC40:4 significantly differentiated AD from CO (p = 0.0009), while four other lipids (PC aaC32:0, PC ae C32:2, PC aeC34:1, and SM(OH)C14:1) differentiated patients with MCI from CO. The combination of three phosphatidylcholines (PC aeC32:2, PC aeC34:1, PCaaC36:5), two lyso-phosphatidylcholines (lysoPC aC18:1, lysoPC aC16:0), and one sphingomyelin (SM(OH) C14:1) constructed a valuable prediction model using the C4.5 decision tree. The diagnosis accuracy for AD versus CO and MCI was 85%. In a blinded follow up conversion study (10 patients with a second blood collection after 9 months), we could verify the clinical diagnosis in 19 out of 20 cases. We propose that soluble platelet PCaeC40:4 is a promising marker to diagnose AD with a cut-off of <0.30μM and that platelets undergo metabolic processes during AD progression.

%B J Alzheimers Dis %V 57 %P 493-504 %8 2017 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/28269764?dopt=Abstract %R 10.3233/JAD-160172