Advanced cerebral amyloid angiopathy and small vessel disease are associated with psychosis in Alzheimer’s disease

Vik‐Mo, Audun Osland; Bencze, János; Ballard, Clive; Hortobágyi, Tibor; Aarsland, Dag

doi:10.1136/jnnp-2018-318445

Cited by 24 publications

(20 citation statements)

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“…Atrophy of the prefrontal cortex has been reported to be associated with the stability of NPS over 6 months, whereas amyloid angiopathy is associated with early and severe psychotic symptoms in diagnosed Alzheimer's disease. 25,26 Few studies have analysed the course of symptoms in LBD compared with Alzheimer's disease, but a 1-year study found similar differences in hallucinations. 27 The differences between Alzheimer's disease and LBD in depression and aggression are in line with studies with shorter duration.…”

Section: Discussionmentioning

confidence: 99%

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The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study

et al. 2019

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IntroductionUnderstanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals.MethodPrimary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia).ResultsWe found that 80% had stable NPI total ≥1, 50% had stable modest NPI total ≥12 and 25% had stable NPI total ≥24 scores. Very severe NPS (≥48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms.ConclusionsWe observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study

et al. 2019

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“…It is therefore possible that small cerebrovascular events triggered by antipsychotic-related excessive sedation, dehydration or orthostatic hypotension [ 45 ] might lead to a deficit in brain perfusion, and the response to this deficit might be exaggerated to toxic levels in the presence of tau pathology, ultimately leading to a hospitalised stroke [ 44 ]. In addition, a recent study of autopsied cases of AD demonstrated that cerebral amyloid angiopathy and advanced small vessel disease were more common in AD patients with psychosis than in those without psychosis [ 15 ]. Although its role in the neurodegenerative process is not fully understood, cerebral amyloid angiopathy weakens cerebral blood vessels [ 46 ] and can lead to microbleeds or larger haemorrhages.…”

Section: Discussionmentioning

confidence: 99%

“…Using routinely collected and clinician-rated 'real-world' data on the hyperactivity and psychosis clusters of neuropsychiatric symptoms in dementia [13], we aimed to investigate whether antipsychotic medications pose different hazards for adverse health outcomes in stratified analyses, in order to evaluate the potential for a more targeted approach to antipsychotic prescribing in dementia. The presence of additional cerebral pathologies in psychosis in dementia [14][15][16][17] suggests higher antipsychotic hazards in this group, but a substantial proportion of patients with psychosis in dementia are not distressed or agitated [18]. As neuropsychiatric symptoms have been reported as potentially stronger correlates of adverse outcomes than their treatments [19] (with agitation possibly yielding a higher risk than psychosis [3]) we hypothesized that patients with psychosis only might be at an increased risk of antipsychotic-related adverse outcomes, while in other groups addressing the impact of the distress/aggression itself might partly counteract the adverse effects of antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic use in dementia: the relationship between neuropsychiatric symptom profiles and adverse outcomes

et al. 2020

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Antipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes-specifically psychosis, agitation, or a combination. A cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in South East London. Neuropsychiatric symptoms closest to first dementia diagnosis were determined according to the Health of the Nation Outcome Scales' mental and behavioural problem scores and the sample was divided into four groups: 'agitation and psychosis', 'agitation, but no psychosis', 'psychosis, but no agitation', and 'neither psychosis nor agitation'. Antipsychotic prescription in a one-year window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all-cause and stroke-specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health. Only in the group 'psychosis, but no agitation' (n = 579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic-associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09-4.25). An increased antipsychotic-related all-cause (adjusted HR 1.14; 95% CI 1.04-1.24) and stroke-specific mortality risk (adjusted HR 1.28; 95% CI 1.01-1.63) was detected in the whole sample, but no interaction between the strata and antipsychotic-related mortality. In conclusion, the adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group.

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“…В последние годы ее нарушение все чаще рассматривается одним из ведущих механизмов прогрессирования церебральной микроангиопатии (англ. small vessel disease/cerebral microangiopathy), являющейся важной причиной когнитивных нарушений и инвалидизации в пожилом возрасте и фактором риска болезни Альцгеймера [26,40]. Долгое время ЦВР изучалась методами транскраниальной допплерографии, ПЭТ, ОФЭКТ с использованием вазодилатирующих стимулов.…”

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Pulsed Arterial Spin Labeling (Pasl) in Receiving Perfusion and Functional Data: Technique Abilities

Sergeeva¹,

Seliverstova²,

Dobryinina³

et al. 2019

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ель исследования. Оценить возможности ASL в оценке нейрональной активации при выполнении когнитивного теста, церебральной перфузии и цереброваскулярной реактивности (R) у здоровых добровольцев. Материалы и методы. Обследовано 12 здоровых добровольцев (возраст 58 лет [57; 59]). МРТ-протокол (Siemens 3.0 Т) включал: Т2, T1mpr, Т2*-градиентное эхо (фМРТ BOLD), PASL (фМРТ ASL). Данные были получены при выполнении задания на управляющие функции мозга (УФМ)-теста Струпа. Цереброваскулярная реактивность (R) оценивалась при вдыхании вазодилатирующей газовой смеси (СО2-6%, О2-21%, N2-73%). Дизайн исследования предполагал получение карт активации ASL и сопоставление с таковыми BOLD, церебральной скорости кровотока (CBF) ASL в периоды активации и покоя при нормокапнии (NC) и гиперкапнии (HC)-CBFrest(HC), CBFactive(HC), CBFrest, CBFactive. R(%)=(CBFrestHC-CBFrestNC)/CBFrestNCх100%. Данные обрабатывались xjView9.0,ASLtbx на базе SPM8; ITK-SNAP. Результаты. При фМРТ ASL выявлены зоны активации, соответствующие фМРТ BOLD. Они включали структуры сетей управляющего контроля и выявления значимости. CBFrest(NC) в зонах активации была выше референсных, CBFactive(NC) превышали CBFrest(NC). Значения CBFactive(HC) были наибольшими и достигали в дополнительной моторной коре 97,6 мл/100г/мин для данной зоны. Только в передней цингулярной коре отмечалось снижение CBFactive(HC). R для зон активации составила 11-21%, больше справа. Обсуждение. Методика фМРТ ASL в оценке УФМ сопоставима с фМРТ BOLD. Значения CBF и R соответствуют таковым при других методах. Количественная оценка CBF в зонах активации позволяет уточнять роль структур в выполнении когнитивного задания в соответствии с профилем задания и рассчитывать адекватность R для его выполнения. Заключение. ASL предоставляет возможность одновременной оценки функциональных и перфузионных данных, что, учитывая отсутствие контрастирования, делает методику крайне перспективной для изучения механизмов нарушения нейроваскулярного взаимодействия в развитии когнитивных расстройств. Ключевые слова: ASL, перфузия головного мозга, скорость мозгового кровотока, CBF, фМРТ, fMRI, сеть управляющего покоя, сеть выявления значимости, цереброваскулярная реактивность.

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Advanced cerebral amyloid angiopathy and small vessel disease are associated with psychosis in Alzheimer’s disease

Cited by 24 publications

References 10 publications

The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study

The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study

Antipsychotic use in dementia: the relationship between neuropsychiatric symptom profiles and adverse outcomes

Pulsed Arterial Spin Labeling (Pasl) in Receiving Perfusion and Functional Data: Technique Abilities

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