Neuropsychiatric symptoms correlated with functional trajectories among people living with Alzheimer’s disease dementia and Lewy body dementia

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

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

The British Journal of Psychiatry ◽

10.1192/bjp.2019.195 ◽

2019 ◽

Vol 216 (1) ◽

pp. 43-48 ◽

Cited By ~ 9

Author(s):

Audun Osland Vik-Mo ◽

Lasse Melvaer Giil ◽

Miguel Germán Borda ◽

Clive Ballard ◽

Dag Aarsland

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neuropsychiatric Symptoms ◽

Personalised Medicine ◽

Lewy Bodies ◽

Lewy Body Dementia ◽

Psychotic Symptoms ◽

Primary Inclusion ◽

The Individual

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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Benzodiazepines and antidepressants: effects on cognitive and functional decline in Alzheimer’s disease and Lewy body dementia

International Journal of Geriatric Psychiatry ◽

10.1002/gps.5494 ◽

2020 ◽

Author(s):

Miguel Germán Borda ◽

Alberto Jaramillo‐Jimenez ◽

Ragnhild Oesterhus ◽

Jose Manuel Santacruz ◽

Diego Alejandro Tovar‐Rios ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Body ◽

Functional Decline ◽

Lewy Body Dementia

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P3-259: Mechanisms of psychomotor slowing in Alzheimer's disease and Lewy body dementia

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1482 ◽

2012 ◽

Vol 8 (4S_Part_15) ◽

pp. P550-P550

Author(s):

Martine Roussel ◽

Olivier Bailon ◽

Olivier Godefroy

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Body ◽

Lewy Body Dementia ◽

Psychomotor Slowing

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Cerebrospinal Fluid Levels of sAPPαand sAPPβin Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates

International Journal of Alzheimer s Disease ◽

10.4061/2011/495025 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Ezra Mulugeta ◽

Elisabet Londos ◽

Oskar Hansson ◽

Clive Ballard ◽

Ragnhild Skogseth ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Lewy Body ◽

Group Analysis ◽

Lewy Body Dementia ◽

Csf Biomarkers ◽

Commercial Kits ◽

Neurochemical Correlates ◽

Fluid Levels

We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPαsAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPαand sAPPβlevels between the groups. Significant correlations were observed between sAPPαand sAPPβand between sAPPβand Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPαand sAPPβlevels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPαcorrelated with p-Tau and sAPPβwith Aβ40. The differential association between sAPPαand sAPPβwith Aβand Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.

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Collusion of α-Synuclein and Aβ aggravating co-morbidities in a novel prion-type mouse model

Molecular Neurodegeneration ◽

10.1186/s13024-021-00486-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Grace M. Lloyd ◽

Jess-Karan S. Dhillon ◽

Kimberly-Marie M. Gorion ◽

Cara Riffe ◽

Susan E. Fromholt ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Body ◽

Amyloid Β ◽

Lewy Body Dementia ◽

Immunohistochemical Analysis ◽

Aggregation Kinetics ◽

Current Area ◽

Old Mice ◽

A Current

Abstract Background The misfolding of host-encoded proteins into pathological prion conformations is a defining characteristic of many neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia. A current area of intense study is the way in which the pathological deposition of these proteins might influence each other, as various combinations of co-pathology between prion-capable proteins are associated with exacerbation of disease. A spectrum of pathological, genetic and biochemical evidence provides credence to the notion that amyloid β (Aβ) accumulation can induce and promote α-synuclein pathology, driving neurodegeneration. Methods To assess the interplay between α-synuclein and Aβ on protein aggregation kinetics, we crossed mice expressing human α-synuclein (M20) with APPswe/PS1dE9 transgenic mice (L85) to generate M20/L85 mice. We then injected α-synuclein preformed fibrils (PFFs) unilaterally into the hippocampus of 6-month-old mice, harvesting 2 or 4 months later. Results Immunohistochemical analysis of M20/L85 mice revealed that pre-existing Aβ plaques exacerbate the spread and deposition of induced α-synuclein pathology. This process was associated with increased neuroinflammation. Unexpectedly, the injection of α-synuclein PFFs in L85 mice enhanced the deposition of Aβ; whereas the level of Aβ deposition in M20/L85 bigenic mice, injected with α-synuclein PFFs, did not differ from that of mice injected with PBS. Conclusions These studies reveal novel and unexpected interplays between α-synuclein pathology, Aβ and neuroinflammation in mice that recapitulate the pathology of Alzheimer’s disease and Lewy body dementia.

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Sundown syndrome in patients with Alzheimer’s disease dementia

Dementia & Neuropsychologia ◽

10.1590/1980-57642018dn13-040015 ◽

2019 ◽

Vol 13 (4) ◽

pp. 469-474 ◽

Cited By ~ 4

Author(s):

Cristiani Sartorio Menegardo ◽

Fernanda Alencar Friggi ◽

Julia Baldon Scardini ◽

Tais Souza Rossi ◽

Thais dos Santos Vieira ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

High Frequency ◽

Neuropsychiatric Symptoms ◽

Time Of Day ◽

Neuropsychiatric Inventory ◽

Cross Sectional ◽

Symptom Intensity ◽

The Family ◽

Alzheimer’S Disease Dementia

ABSTRACT The sundown syndrome is a complex neurobehavioral disorder in patients with dementia associated with high financial cost and significant caregiver burden. It is a multifactorial phenomenon with unclear pathophysiology, characterized by the presence of neuropsychiatric symptoms in the evening period. Objective: To analyze the main neuropsychiatric symptoms, their correlation with one another, with comorbidities, and with time of day of greatest symptom intensity in patients with Alzheimer’s disease dementia. Methods: This is a cross-sectional, observational and explanatory study in which caregivers/relatives of elderly patients with dementia were interviewed using a structured tool called the Neuropsychiatric Inventory (NPI). Results: The sample studied was composed of 38 patients, 60.5% female and 39.5% male, with mean age of 81±6 (67-94) years. A high frequency of neuropsychiatric symptoms in the evening period was observed, predominantly irritability (55.3%), nocturnal behavior (47.4%), and aggressiveness (42.1%). Only 36.8% of the family caregivers used non-pharmacological strategies. Conclusion: The frequency of neuropsychiatric symptoms was exacerbated in the evening among patients with Alzheimer’s disease, especially for those behavioral symptoms that had a positive correlation with one another.

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