Evidence of compensation in the brain networks of Lewy body dementia and Alzheimer’s disease patients

AbstractDementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) require differential management despite presenting with symptomatic overlap. A human electrophysiological difference is a decrease of dominant frequency (DF) −the highest power frequency between 4-15Hz– in DLB; a characteristic of Parkinsonian diseases. We analysed electroencephalographic (EEG) recordings from old adults: healthy controls (HCs), AD, DLB and Parkinson’s disease dementia (PDD) patients. Brain networks were assessed with the minimum spanning tree (MST) within six EEG bands: delta, theta, high-theta, alpha, beta and DF. Patients showed lower alpha band connectivity and lower DF than HCs. Lewy body dementias showed a randomised MST compared with HCs and AD in high-theta and alpha but not within the DF. The MST randomisation in DLB and PDD reflects decreased brain efficiency as well as impaired neural synchronisation. However, the lack of network topology differences at the DF indicates a compensatory response of the brain to the neuropathology.

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Dementia with Lewy bodies

Advances in Psychiatric Treatment ◽

10.1192/apt.4.6.360 ◽

1998 ◽

Vol 4 (6) ◽

pp. 360-363 ◽

Cited By ~ 1

Author(s):

E. Jane Byrne

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Body ◽

Senile Dementia ◽

Lewy Bodies ◽

Lewy Body Dementia ◽

Body Type ◽

Clinical Criteria ◽

Dementia Syndrome ◽

Distinct Disease

Dementia with cortical Lewy bodies (LBD) was first described by Okazakiet alin 1961 and is now recognised as a relatively common cause of the dementia syndrome. The true prevalence of LBD is unknown. In post-mortem studies of patients diagnosed as having dementia in life, the mean frequency of Lewy body dementia is 12.5% (Byrne, 1997). Clinically diagnosed LBD (using operational clinical criteria) is found in 10–23% of patients presenting to, or in the care of, psychogeriatric services (Collertonet al, 1996). What is not yet certain is its nosological status; opinion is divided between regarding it as a variety of Alzheimer's disease (the Lewy body variant), a distinct disease (senile dementia of the Lewy body type) or a spectrum disorder related to both Parkinson's disease and to Alzheimer's disease (Byrne, 1992).

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P.052 Understanding the influence of APOE-ɛ4 on magnetic resonance imaging-based hippocampal phenotypes in Alzheimer’s disease and Lewy body dementia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.333 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S34-S34

Author(s):

U Saeed ◽

P Desmarais ◽

M Masellis

Keyword(s):

Magnetic Resonance Imaging ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Magnetic Resonance ◽

Lewy Body ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Lewy Body Dementia ◽

Hippocampal Atrophy ◽

Resonance Imaging

Background: The ɛ4-allele of apolipoprotein E (APOE-ɛ4) increases the risk not only for Alzheimer’s disease (AD), but also for Parkinson’s disease dementia and dementia with Lewy bodies (collectively, Lewy body dementia [LBD]). Hippocampal volume is an important neuroimaging biomarker for AD and LBD, although its association with APOE-ɛ4 is inconsistently reported. We investigated the association of APOE-ε4 with hippocampal atrophy quantified using magnetic resonance imaging in AD and LBD. Methods: Electronic databases (PubMed, Embase, PsycINFO, Scopus, Web of Science) were systematically searched for studies published up until December 31st, 2020. Results: Thirty-nine studies (25 cross-sectional, 14 longitudinal) were included. We observed that: (1) APOE-ε4 was associated with greater rate of hippocampal atrophy in AD and those who progressed from mild cognitive impairment to AD, (2) APOE-ε4 carriers showed greater involvement of cornu ammonis-1 hippocampal subfield versus non-carriers in AD, (3) APOE-ɛ4 may influence hippocampal atrophy in dementia with Lewy bodies, although longitudinal investigations are required, and (4) APOE-ε4 associated with earlier rather than very late expression of mediotemporal degeneration and memory-related neurocognitive impairment. Conclusions: The role of APOE-ɛ4 in modulating hippocampal phenotypes may be further clarified through more homogenous, well-powered, pathology-proven studies. Understanding the underlying mechanisms will facilitate development of prevention strategies targeting APOE-ɛ4.

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Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies

The British Journal of Psychiatry ◽

10.1192/bjp.bp.108.052050 ◽

2009 ◽

Vol 194 (1) ◽

pp. 34-39 ◽

Cited By ~ 85

Author(s):

John T. O'Brien ◽

Ian G. McKeith ◽

Zuzana Walker ◽

Klaus Tatsch ◽

Jan Booij ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diagnostic Accuracy ◽

Lewy Body ◽

Dementia With Lewy Bodies ◽

Photon Emission ◽

Lewy Bodies ◽

Lewy Body Dementia ◽

Emission Computed Tomography

Background123I-FP-CIT SPECT (single photon emission computed tomography) can help in the differential diagnosis of probable dementia with Lewy bodies (Lewy body dementia) and Alzheimer's disease.AimsOur aim was to determine the accuracy of 123I-FP-CIT SPECT in diagnosing people with possible dementia with Lewy bodies.MethodWe undertook a 12-month follow-up of 325 individuals with probable or possible Lewy body or non-Lewy body dementia who had previously undergone 123I-FP-CIT SPECT. A consensus panel masked to SPECT findings, established diagnosis at 12 months in 264 people.ResultsOf 44 people with possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19 people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body dementia (16%) and for 18 individuals it remained possible dementia with Lewy bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7 individuals with a possible diagnosis who were diagnosed as having Alzheimer's disease at follow-up had normal scans (specificity 100%).ConclusionsOur findings confirm the diagnostic accuracy of 123I-FP-CIT SPECT in distinguishing Lewy body from non-Lewy body dementia and also suggest a clinically useful role in diagnostically uncertain cases, as an abnormal scan in a person with possible dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.

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α-Synuclein Heteromers in Red Blood Cells of Alzheimer’s Disease and Lewy Body Dementia Patients

Journal of Alzheimer s Disease ◽

10.3233/jad-201038 ◽

2021 ◽

Vol 80 (2) ◽

pp. 885-893

Author(s):

Simona Daniele ◽

Filippo Baldacci ◽

Rebecca Piccarducci ◽

Giovanni Palermo ◽

Linda Giampietri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Diagnostic Accuracy ◽

Red Blood Cells ◽

Blood Cells ◽

Lewy Body ◽

Lewy Bodies ◽

Amyloid Β ◽

Lewy Body Dementia

Background: Red blood cells (RBCs) contain the majority of α-synuclein (α-syn) in blood, representing an interesting model for studying the peripheral pathological alterations proved in neurodegeneration. Objective: The current study aimed to investigate the diagnostic value of total α-syn, amyloid-β (Aβ1–42), tau, and their heteroaggregates in RBCs of Lewy body dementia (LBD) and Alzheimer’s disease (AD) patients compared to healthy controls (HC). Methods: By the use of enzyme-linked immunosorbent assays, RBCs concentrations of total α-syn, Aβ1–42, tau, and their heteroaggregates (α-syn/Aβ1–42 and α-syn/tau) were measured in 27 individuals with LBD (Parkinson’s disease dementia, n = 17; dementia with Lewy bodies, n = 10), 51 individuals with AD (AD dementia, n = 37; prodromal AD, n = 14), and HC (n = 60). Results: The total α-syn and tau concentrations as well as α-syn/tau heterodimers were significantly lower in the LBD group and the AD group compared with HC, whereas α-syn/Aβ1–42 concentrations were significantly lower in the AD dementia group only. RBC α-syn/tau heterodimers had a higher diagnostic accuracy for differentiating patients with LBD versus HC (AUROC = 0.80). Conclusion: RBC α-syn heteromers may be useful for differentiating between neurodegenerative dementias (LBD and AD) and HC. In particular, RBC α-syn/tau heterodimers have demonstrated good diagnostic accuracy for differentiating LBD from HC. However, they are not consistently different between LBD and AD. Our findings also suggest that α-syn, Aβ1–42, and tau interact in vivo to promote the aggregation and accumulation of each other.

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A comparison of the prevalence of Fear of Falling between older patients with Lewy body dementia, Alzheimer's disease, and without dementia

Experimental Gerontology ◽

10.1016/j.exger.2021.111248 ◽

2021 ◽

Vol 146 ◽

pp. 111248

Author(s):

Pinar Soysal ◽

Semen Gokce Tan ◽

Lee Smith

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Body ◽

Older Patients ◽

Fear Of Falling ◽

Lewy Body Dementia

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Aging & Dementia - 4 Risk Factors for Earlier Onset of Dementia in Pure Alzheimer’s Disease, Mixed Alzheimer’s with Lewy Bodies, and Pure Lewy Body Disease: Autopsy-Confirmed Cases from the National Alzheimer’s Coordinating Center

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acy060.04 ◽

2018 ◽

Vol 33 (6) ◽

pp. 692-702

Author(s):

J Schaffert ◽

C LoBue ◽

L Lacritz ◽

K Wilmoth ◽

T Nguyen ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Body ◽

Lewy Bodies ◽

Lewy Body Disease

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Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer’s disease

International Psychogeriatrics ◽

10.1017/s1041610220003944 ◽

2021 ◽

pp. 1-6

Author(s):

Julia Schumacher ◽

Alan J. Thomas ◽

Luis R. Peraza ◽

Michael Firbank ◽

John T. O’Brien ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Functional Connectivity ◽

Lewy Body ◽

Cholinergic System ◽

Structural Changes ◽

Lewy Body Dementia ◽

Occipital Cortex ◽

Nucleus Basalis ◽

Nucleus Basalis Of Meynert

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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