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Advanced Neurology Improving cognitive development in Down syndrome

which DYRK1A and APP are highly expressed in early the organic aspect targeted, drug safety, applicability,
development. A few genes involved in neuron maturation short- and longer-term effects, and people’s intrinsic
anomalies have also been identified. They include DSCAM variability.
that plays a role in dendritic and synaptic development.
The same authors have provided a meta-analysis of 5. Cognitive behavioral interventions
40 prenatal and neonatal pharmacological attempts to This type of intervention started being developed several
improve neurogenesis and neural connectivity in DS mice decades ago in response to the wishes of the associations and
using either natural or non-natural substances. the parents of children with DS and it has been refined and
The resulting picture varies with the product and the extended since through clinical and experimental research.
developmental aspect considered. Study that targeted This type of intervention should not be confounded with
neural progenitor cells with natural substances showed psychotherapy that relates to attempts to help people cope
a short-term effect, except melatonin that had no effect. with their psychological and psychiatric problems.
Among non-natural substances, chlorhydrate of fluoxetine Memory and language are the most important areas in
(a selective inhibitor of the recapture of neurotransmitter cognitive functioning. They are interdependent functions.
serotonine) was the only one to have an effect. Regarding Language implies good short- and longer-term storage
dendritic development, the effects of all substances tended abilities. Memory is largely based on linguistic coding. In
to fade over time. 28 what follows, one specifies the course of current behavioral
Natural substances, except oleic acid, administered interventions in memory and language with children and
during the first two postnatal weeks (corresponding to the adolescents with DS.
third trimester of gestation in humans) have only a short-
term effect on hippocampal proliferation and dendritic 5.1. Memory intervention
development. In contrast, study with non-natural What we call memory is an interconnected set of treatment
substances demonstrated longer-term efficiency. 28 and storage systems and sub-systems. A key distinction is
between short-term (also called working) memory (STM)
The neurobiology of DS also results in a reduction of
synaptic density and plasticity. Much attention has been maintaining the information active for a few seconds before
devoted to the neurotransmitters. Gotti et al. have reviewed eliminating or transferring it to the long-term store (LTM).
29
a series of studies on the alterations of brain circuits that Evidence suggests that the auditory-vocal store (AV-STM)
and the visual-spatial one (VS-STM) are separate entities.
can be identified in murine models of DS. It shows that LTM is also divided along several lines: explicit (conscious)
different neurotransmission systems are downgraded
in several cerebral regions including the hippocampus, and implicit (non-conscious) components. The former is
the locus coeruleus, and the frontal cortex. Drugs are in related to declarative memory (recording facts and events),
the pipeline for reducing the neurotransmission deficits the latter to procedural memory (recording sequential
31
caused by DS. A current strategy is to inhibit the enzymatic procedures for doing things).
cleavage of the neurotransmitter in the synaptic space. A long-standing finding in the DS literature is that
32
Bartesaghi et al. have analyzed the results of a series AV-STM is more impaired relative to VS-STM. In most
30
of experimental and clinical attempts to upgrade the individuals with DS, the AV-STM span is limited to a few
33
cholinergic, the glutamatergic, and the GABAergic systems items. They tend not to repeat verbal sequences, which,
in DS. They found no solid support for the treatments as a result, rapidly decay. The major sub-component in
Baddeley’s working memory scheme is an articulatory
aiming at increasing acetylcholine recapture in children,
adolescents, and young adults with DS. In contrast, control process based on sub-vocal rehearsal and operating
treatment with the NMDA (N-methyl-D-aspartic acid) on a phonological loop. The limitations in AV-STM in
receptor antagonist memantine (a molecule that mimics individuals with DS are linked to dysfunctional aspects
the action of neurotransmitter glutamate) improves of their speech. Their articulatory development is delayed
34
cognitive measures in TS65Dn mice and young adults with and often incomplete.
DS. Individual variability is important. Many participants Neuropsychological studies show that the memory
in the human studies show little to no gain but a subset of limitations in DS correspond to the underdevelopment of
individuals respond positively to the drugs. 30 the hippocampal and prefrontal systems, and possibly the
cerebellar structures. 35
Brain pharmacotherapy is still in its beginning stages.
The equation is complex. It involves several interacting Remediation efforts target the articulatory control
variables: the precise calendar of development as to process of AV-STM for increasing its span. Results show

Volume 4 Issue 1 (2025) 4 doi: 10.36922/an.3785