Cognitive decline and dementia in Down syndrome

Down syndrome disintegrative disorder (DSDD) is a condition of unknown etiology characterized by acute cognitive decline, catatonia, insomnia, and autistic features in individuals with Down syndrome. A prior report of four patients with DSDD suggested a potential autoimmune etiology based on the presence of autoantibodies and on successful treatment with immunotherapy that included intravenous immunoglobulin (IVIG). Herein, we present the case of an 8-year old girl who developed acute cognitive decline to a dementia-like state, insomnia, catatonia, and autistic features. In contrast to the four patients with DSDD above, she had no evidence of autoimmunity and presented at a younger age. Given the gravity of her acute deterioration and the exclusion of other etiologies, she was treated with immunotherapy presumptively. She responded with near complete resolution of symptoms, but demonstrated a pattern of mild decline as she approached each monthly dosing of IVIG and steroids, reversed by treatment. Mycophenolate mofetil (MMF) was therefore added, with stability throughout the month and the ability to taper off IVIG. After stopping IVIG, she had a mild recurrence of symptoms that again resolved with repeat IVIG followed by tapering off. Outcome was assessed at 2.5 years after presentation, at which time she was back to her premorbid condition, except for persistent tics off immunotherapy. This case supports the contention that patients with a rapid onset of severe symptoms consistent with DSDD, who have a thorough evaluation with the exclusion of other etiologies, may warrant a trial of immunotherapy with steroids, IVIG and/or other agents like MMF even in the absence of evidence of autoimmunity on standard evaluation.

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Poor Sleep as a Precursor to Cognitive Decline in Down Syndrome : A Hypothesis

Journal of Alzheimer’s Disease & Parkinsonism ◽

10.4172/2161-0460.1000124 ◽

2013 ◽

Vol 03 (03) ◽

Cited By ~ 4

Author(s):

Fabian Fernandez Jamie O Edgin

Keyword(s):

Down Syndrome ◽

Cognitive Decline ◽

Poor Sleep

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What We Should Not Forget about Down Syndrome

Neurographics ◽

10.3174/ng.2000043 ◽

2021 ◽

Vol 11 (3) ◽

pp. 149-165

Author(s):

D.C. Fragoso ◽

D.M. Nunes ◽

A.C.M. Maia ◽

L.A.L. Garcia ◽

H.C.B.R. Alves ◽

...

Keyword(s):

Down Syndrome ◽

Intellectual Disability ◽

Cognitive Decline ◽

Early Recognition ◽

Point Of View ◽

Chromosome 21 ◽

Age Related ◽

Organ Systems ◽

Notable Increase ◽

Age Related Cognitive Decline

Down syndrome is the foremost common genetic cause of intellectual disability. The additional copy of chromosome 21 confers potential changes in virtually all organ systems, including the brain, neck structures, and spine. Neuroradiologists should be aware of the multitude of imaging findings in patients with Down syndrome to correctly identify and diagnose life-altering conditions associated with this syndrome. In particular, the high prevalence of age-related cognitive decline and dementia stands out more clearly in recent decades due to the notable increase in these individuals' survival. Although the early and timely diagnosis of cognitive decline in patients with varying degrees of intellectual disability has not been an easy task from the clinical point of view, anatomic and functional brain studies have shown an essential role because they allow the early recognition of abnormalities that precede the cognitive decline. Furthermore, the similarities and differences in neuropathologic, genetic, and imaging aspects in patients with Down syndrome have allowed extrapolation for a better understanding of the mechanisms linked to Alzheimer disease development.Learning Objective: To review and systematize the distinctive characteristics and abnormalities of the head and neck, vertebral column, and CNS present in Down syndrome

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Dynamic Causal Modeling of the Relationship between Cognition and Theta–alpha Oscillations in Adults with Down Syndrome

Cerebral Cortex ◽

10.1093/cercor/bhz043 ◽

2019 ◽

Vol 29 (5) ◽

pp. 2279-2290 ◽

Cited By ~ 7

Author(s):

Sarah Hamburg ◽

Richard Rosch ◽

Carla Marie Startin ◽

Karl John Friston ◽

André Strydom

Keyword(s):

Down Syndrome ◽

Cognitive Decline ◽

Cognitive Ability ◽

Causal Modeling ◽

Dynamic Causal Modeling ◽

Network Parameter ◽

Inhibitory Mechanisms ◽

Neuronal Inhibition ◽

Ultra High Risk ◽

Eeg Recordings

Abstract Individuals with Down syndrome (DS) show high inter-subject variability in cognitive ability and have an ultra-high risk of developing dementia (90% lifetime prevalence). Elucidating factors underlying variability in cognitive function can inform us about intellectual disability (ID) and may improve our understanding of factors associated with later cognitive decline. Increased neuronal inhibition has been posited to contribute to ID in DS. Combining electroencephalography (EEG) with dynamic causal modeling (DCM) provides a non-invasive method for investigating excitatory/inhibitory mechanisms. Resting-state EEG recordings were obtained from 36 adults with DS with no evidence of cognitive decline. Theta–alpha activity (4–13 Hz) was characterized in relation to general cognitive ability (raw Kaufmann’s Brief Intelligence Test second Edition (KBIT-2) score). Higher KBIT-2 was associated with higher frontal alpha peak amplitude and higher theta–alpha band power across distributed regions. Modeling this association with DCM revealed intrinsic self-inhibition was the key network parameter underlying observed differences in 4–13 Hz power in relation to KBIT-2 and age. In particular, intrinsic self-inhibition in right V1 was negatively correlated with KBIT-2. Results suggest intrinsic self-inhibition within the alpha network is associated with individual differences in cognitive ability in adults with DS, and may provide a potential therapeutic target for cognitive enhancement.

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