Factors associated with behavioral and psychological symptoms of dementia

Most people with dementia suffer behavioral and psychological symptoms (BPSD). These symptoms add to caregiver stress and accelerate cognitive decline. The etiology of BPSD is complex, with multiple factors influencing symptom manifestation. The ability to accommodate and communicate needs decreases with cognitive deterioration. Unmet needs may explain why some individuals, despite having the same diagnosis and degree of cognitive impairment, have more severe BPSD. BPSD is treated with both atypical and typical antipsychotics (APD). Numerous studies demonstrated that APD treatment in individuals with dementia might cause major side effects, including death. The purpose of this Thesis is to examine factors associated with BPSD in a large group of individuals with dementia. The Thesis covers four cross-sectional investigations using data from five Swedish registries: The Swedish registry for cognitive/dementia disorders (SveDem), the Swedish Behavioral and psychological symptoms of dementia Registry (BPSD registry), the Swedish Prescribed Drug Registry (SPDR), the Swedish Cause of Death Registry (CODR), and the Swedish National Patient Registry (NPR). Six types of diagnoses were included in the studies: Alzheimer’s disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and unspecified dementia (UNS). In Study 1, we discovered that 75% of individuals with dementia exhibited at least one clinically significant BPSD, the most prevalent being aberrant motor behavior, agitation/aggression and irritability. In comparison to AD, we found a lower risk of delusions (in FTD, UNS), hallucinations (FTD), agitation (VaD, PDD, UNS), elation/euphoria (DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD); irritability (in DLB, FTD, UNS), aberrant motor behavior (Mixed, VaD, UNS), sleep and night-time behavior changes (UNS). Higher risk of delusions (DLB), hallucinations (DLB, PDD), apathy (VaD, FTD), disinhibition (FTD) and appetite and eating abnormalities (FTD) were also found in comparison to AD. In Study 2, pain was the most prevalent unmet need, followed by sleeping disturbances, impaired hearing and impaired vision. Additionally, we found that the risk of BPSD increases with unmet physical or psychological needs in dementia. In Study 3, APD use at the time of dementia diagnosis was associated with increased mortality risk across the cohort and by dementia subtype. In Study 4, we found that out of 53,384 individuals with dementia, 1,823 owned a firearm and 419 were unfit owners. Owners of firearms were mostly male, younger, living alone and without homecare support. Living with another person, frontotemporal dementia, APD and hypnotics prescription, being diagnosed in a memory/cognitive clinic, female gender, and mild and moderate dementia were the most important predictors of being reported to the police. In conclusion, individuals with dementia who live in long-term care facilities frequently develop BPSD. Additionally, unmet needs are significantly associated with BPSD in each dementia type. Individuals with dementia receive both typical and atypical APDs, however, their use is associated with an increased risk of death. Finally, we found that the decision to withdraw the firearm is based on a variety of clinical factors associated with dementia

Feasibility and usability of remote monitoring in Alzheimer’s disease

Introduction: Remote monitoring technologies (RMTs) can measure cognitive and functional decline objectively at-home, and offer opportunities to measure passively and continuously, possibly improving sensitivity and reducing participant burden in clinical trials. However, there is skepticism that age and cognitive or functional impairment may render participants unable or unwilling to comply with complex RMT protocols. We therefore assessed the feasibility and usability of a complex RMT protocol in all syndromic stages of Alzheimer’s disease and in healthy control participants.Methods: For 8 weeks, participants (N=229) used two activity trackers, two interactive apps with either daily or weekly cognitive tasks, and optionally a wearable camera. A subset of participants participated in a 4-week sub-study (N=45) using fixed at-home sensors, a wearable EEG sleep headband and a driving performance device. Feasibility was assessed by evaluating compliance and drop-out rates. Usability was assessed by problem rates (e.g., understanding instructions, discomfort, forgetting to use the RMT or technical problems) as discussed during bi-weekly semi-structured interviews.Results: Most problems were found for the active apps and EEG sleep headband. Problem rates increased and compliance rates decreased with disease severity, but the study remained feasible.Conclusions: This study shows that a highly complex RMT protocol is feasible, even in a mild-to-moderate AD population, encouraging other researchers to use RMTs in their study designs. We recommend evaluating the design of individual devices carefully before finalizing study protocols, considering RMTs which allow for real-time compliance monitoring, and engaging the partners of study participants in the research.<br/

Engagement of attention by evolutionary-relevant visual stimuli across menstrual cycle

Wahania w stężeniach hormonów związane z cyklem miesiączkowym wpływają na nastrój, funkcje poznawcze i zachowanie kobiet. Podczas gdy w okresie przedowulacyjnym (faza folikularna) kobiety są bardziej wrażliwe na bodźce istotne reprodukcyjnie, to w fazie lutealnej bardziej zwracają uwagę na bodźce związane z ryzykiem przerwania ciąży. Zmiany w percepcji mierzone za pomocą okulografu powinny odzwierciedlać zmiany w zaangażowaniu uwagi w przetwarzanie bodźców istotnych ewolucyjnie. Uczestniczki (N = 20) zbadano dwukrotnie: w fazie lutealnej i folikularnej. Stężenie progesteronu w ślinie zmierzono za pomocą testu immunoenzymatycznego (ELISA). Podczas obu sesji zaprezentowano ten sam zestaw stu dwudziestu zdjęć należących do sześciu kategorii emocjonalnych: dzieci, wysoka kalorii żywności, żywność o niskiej kaloryczności, zagrożenie, obiekty obrzydliwe i sceny erotyczne. Zdjęcia podzielono na obszary kluczowe dla kategorii (np. postać agresora w przypadku zagrożenia) i tło. Zdjęcia wyświetlane były przez 5 sekund. W tym czasie rejestrowano ruchy oczu. Liczbę fiksacji padających w rejon kluczowy porównano między dwiema fazami cyklu menstruacyjnego.Średnia liczba fiksacji przed trafieniem w obszar zainteresowania była mniejsza fazie lutealnej (1,83) w porównaniu do fazy folikularnej (2,02); t(1,19)=27, p=.014. W fazie lutealnej pierwsza fiksacja padała częściej w kluczowe rejony zdjęć kategorii dzieci, t(19) = 2,4, p = .026) oraz zagrożenie; t(19) = 3,0, p = .007) w porównaniu do fazy folikularnej. Tendencja ta utrzymywała się w czasie w przypadku zagrożenia; t (19) = 2,2, p = .042. Czas przejścia fiksacji z obszarów wstrętnych był istotnie krótszy w fazie lutealnej w porównaniu do fazy folikularnej; t(19) = 2,18, p = .042.Faza cyklu miesiączkowego moduluje automatyczne przechwytywanie uwagi, wpływając na prawdopodobieństwo trafienia pierwszej fiksacji w kluczowe elementy znaczących obiektów. W fazie lutealnej kobieta może być w ciąży, co pociąga za sobą zwiększenie zaangażowanie uwagi w percepcję dzieci i ułatwia wykrywanie zagrożeń. Tendencję do unikania ryzyka odzwierciedla również utrzymywanie uwagi przez bodźce zagrażające.Variations in hormone levels across the menstrual cycle affect women's mood, cognition and behavior. Particularly, during the pre-ovulatory (follicular) phase women are more sensitive to reproductively-relevant stimuli, while in the post-ovulatory (luteal) phase they are sensitive to stimuli related to risk of pregnancy termination. The engagement of attention by evolutionary-relevant stimuli measured using eye-tracking should reflect changes in this sensitivity.Female participants (N=20) were tested twice, first in the luteal and then in the follicular phase, or vice-versa. Saliva levels of progesterone were analysed using enzyme-linked immunosorbent assay (ELISA). During both experimental sessions the same set of one hundred and twenty images from six evolutionary-relevant categories were presented: Children, High-calorie food, Low-calorie food, Threat, Disgusting objects, and Erotic scenes. Images were segmented to key region (e.g., figure of an aggressor in case of Threat) and background. Eye movements were recorded during 5-second presentation of each image. Number of fixations in the key region were compared in the two menstrual phases.The number of fixations prior to the first fixation within the key regions averaged for all categories was smaller in the luteal phase (1,83) comparing to follicular phase (2,02), t(1,19)=27, p=.014. In the luteal phase first fixation fell more often in the key regions of Children (t(19) = 2.4, p = .026) and Threat images (t(19) = 3.0, p = .007) than in the follicular phase. This tendency was sustained during following fixations in case of Threat; t(19) = 2.2, p=.042. First-pass duration of fixations in the regions of Disgusting objects showed a significant difference between follicular and luteal phase: t(19)=2.18 , p=.042.Phase of the menstrual cycle influenced automatic and rapid capture of attention, as it modulated chance of the first fixation being drawn towards meaningful objects. In the luteal phase woman might be pregnant, which may cause enhanced attending to children and facilitation of detecting danger. The tendency to avoid risk is also reflected by sustained attention towards threatening objects

"Prolactin in response to psychological stress in humans"

Prolaktyna jest hormonem peptydowym syntetyzowanym i wydzielanym głównie przez komórki laktotropowe przedniej części przysadki mózgowej. Hormon ten ma właściwości plejotropwe – bierze on udział w wielu różnych procesach zachodzących w organizmie. Z punktu widzenia tej pracy najważniejsza jest rola prolaktyny w adaptacji do sytuacji stresowych. Kluczowym czynnikiem związanym z wydzielaniem prolaktyny w stresie wydaje się być postrzegana kontrola nad rzeczywistością. Zaobserwowano istotny związek między brakiem kontroli a podniesionym stężeniem prolaktyny. Podejrzewa się, że funkcją prolaktyny w reakcji stresowej jest ochrona przed negatywnymi konsekwencjami działania glukokortykoidów. W przypadku przedłużającego się stresu może rozwinąć się stan chronicznie podniesionego stężenia prolaktyny – hiperprolaktynemia, którą wiązać się może z poważnymi konsekwencjami zdrowotnymi u chorych, w tym problemami z bezpłodnością.Prolactin is a peptide hormone primarily synthesized and secreted by lactotroph cells of anterior pituitary. Prolactin has pleiotropic effect - it is involved in many different processes in the body. However, in the centre of interest of this work is the most important action of prolactin e.g. its role in adaptation to stressful situations. The key factor associated with prolactin production and stress is locus of control. There is a significant relationship between lack of control over reality and elevated level of prolactin. It has been suggested that the function of prolactin in stress response is to protect organism against the negative consequences of the action of glucocorticoids. Prolonged stress may lead to a chronic state of elevated level of prolactin - hyperprolactinemia, which can be associated with serious health consequences, including fertility problems

Cholinesterase inhibitors in patients with diabetes mellitus and dementia: an open-cohort study of ~23 000 patients from the Swedish Dementia Registry

ObjectiveCholinesterase inhibitors (ChEIs) and memantine are the only approved pharmacological treatments for Alzheimer’s disease (AD). Recent literature suggests reductions in cardiovascular burden and risk of stroke in ChEI users. However, the clinical effectiveness of these drugs in patients with diabetes mellitus (DM) and dementia has not been evaluated.Research design and methodsWe conducted a registry-based open-cohort study of 22 660 patients diagnosed with AD and mixed-pathology dementia registered in the Swedish Dementia Registry until December 2015. Information on drug use, comorbidity and mortality was extracted using the linkage with the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. In total, 3176 (14%) patients with DM and 19 484 patients without DM were identified. Propensity-score matching, Cox-regression and competing-risk regression models were applied to produce HRs with 95% CIs for differences in all-cause, cardiovascular and diabetes-related mortality rates in ChEI users and non-users.ResultsAfter matching the ChEI use in patients with DM was associated with 24% all-cause mortality reduction (HR 0.76 (95% CI 0.67 to 0.86)), compared with 20% reduction (0.80 (0.75 to 0.84)) in non-DM users. Donepezil and galantamine use were associated with a reduced mortality in both patients with DM (0.84 (0.74 to 0.96); 0.80 (0.66 to 0.97)) and patients without DM (0.85 (0.80 to 0.90); 0.93 (0.86 to 0.99)). Donepezil was further associated with reduction in cardiovascular mortality, however only in patients without DM (0.84 (0.75 to 0.94)). Rivastigmine lowered mortality only in the whole-cohort analysis and in patients without DM (0.82 (0.75 to 0.89)). Moreover, ChEI use was associated with 48% reduction in diabetes-related mortality (HR 0.52 (0.32 to 0.87)) in the whole-cohort analysis. Last, low and high doses were associated with similar benefit.ConclusionsWe found reductions in mortality in patients with DM and AD or mixed-pathology dementia treated with ChEIs, specifically donepezil and galantamine were associated with largest benefit. Future studies should evaluate whether ChEIs help maintain self-management of diabetes in patients with dementia

Behavioral and Psychological Symptoms of Dementia in Different Dementia Disorders : A Large-Scale Study of 10,000 Individuals

Background: The majority of individuals with dementia will suffer from behavioral and psychological symptoms of dementia (BPSD). These symptoms contribute to functional impairment and caregiver burden. Objective: To characterize BPSD in Alzheimer's disease (AD), vascular dementia (VaD), mixed (Mixed) dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and unspecified dementia in individuals residing in long-term care facilities. Methods: We included 10,405 individuals with dementia living in long-term care facilities from the Swedish registry for cognitive/dementia disorders (SveDem) and the Swedish BPSD registry. BPSD was assessed with the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). Multivariate logistic regression models were used to evaluate the associations between dementia diagnoses and different BPSDs. Results: The most common symptoms were aberrant motor behavior, agitation, and irritability. Compared to AD, we found a lower risk of delusions (in FTD, unspecified dementia), hallucinations (FTD), agitation (VaD, PDD, unspecified dementia), elation/euphoria (DLB), anxiety (Mixed, VaD, unspecified dementia), disinhibition (in PDD), irritability (in DLB, FTD, unspecified dementia), aberrant motor behavior (Mixed, VaD, unspecified dementia), and sleep and night-time behavior changes (unspecified dementia). Higher risk of delusions (DLB), hallucinations (DLB, PDD), apathy (VaD, FTD), disinhibition (FTD), and appetite and eating abnormalities (FTD) were also found in comparison to AD. Conclusion: Although individuals in our sample were diagnosed with different dementia disorders, they all exhibited aberrant motor behavior, agitation, and irritability. This suggests common underlying psychosocial or biological mechanisms. We recommend prioritizing these symptoms while planning interventions in long-term care facilities

Antipsychotic Treatment Associated With Increased Mortality Risk in Patients With Dementia. A Registry-Based Observational Cohort Study

Objective: To assess all-cause mortality patients with dementia treated with typical and atypical antipsychotic drugs (APDs). Design: Registry-based cohort study. Setting and participants: A total of 58,412 patients diagnosed with dementia and registered in the Swedish Dementia Registry were included in the study. Of the study sample, 2526 of the patients were prescribed APDs. Of these, 602 patients were prescribed typical APDs and 1833 patients were prescribed atypical APDs. Ninety-one patients were prescribed both typical and atypical APDs. Measurements: All-cause mortality based on Swedish Cause of Death Register. Adjusted hazard ratios of mortality were calculated according to class of APDs (typical or atypical) prescribed. Final models were adjusted for age at dementia diagnosis, sex, Charlson comorbidity index, living arrangement, and Mini-Mental State Examination. Results: In the adjusted models, use of APDs at the time of dementia diagnosis was associated with increased mortality risk in the total cohort (hazard ratio = 1.4; 95% confidence interval 1.3–1.5). After stratifying for dementia types, increased mortality risks associated with APDs were found in patients with Alzheimer's disease, mixed dementia, unspecified dementia, and vascular dementia. Higher risk for mortality was found with typical APDs in patients with mixed and vascular dementia and with atypical APDs in patients with Alzheimer's disease, mixed, unspecified, and vascular dementia. Furthermore, in patients with Alzheimer's disease who had typical APDs, use lower risk of death emerged in comparison with patients with atypical APDs. Conclusions/Implications: Both the use of atypical and typical APDs increased the risk of death in patients with dementia even after adjusting for differences in basic characteristics between groups. Although we cannot rule out the influence of residual confounding, these results would seem to add to studies suggesting caution in APD prescription for patients with dementia