Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review

Abstract

Background: There is a proven link between Down syndrome and the early development of the neuropathological features of Alzheimer's disease (AD). Changes in the personality and behavior of adults with Down syndrome might indicate the early stages of dementia or of frontotemporal lobar degeneration. The objective of this study was to investigate the executive functions and changes in behavior associated with frontal lobe degeneration in individuals with Down syndrome who develop AD. We conducted a systematic review selecting studies employing cognitive assessments. Summary: We identified few studies using objective measurements to determine whether cognitive aspects associated with the frontal lobe correlate with dementia in this population. We observed a tendency toward such correlations. Key Messages: There is a need for further studies in which objective measures of cognitive and behavioral factors are evaluated together with data related to brain function and morphology.

Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in-vivo fetal and neonatal MRI assessment

“…The brachycephalic skull reflects a similarly shaped brain and is considered to be a consequence of relatively smaller frontal lobes in DS 46 . Frontal lobe dysfunction and structural changes have previously been associated with early manifestations of Alzheimer's disease in the adult DS population 47,48 . Further analysis of regional brain volumes in early postnatal development will allow us to explore the relationship between frontal lobe development and childhood cognitive abilities.…”

“Mi niño ya no es mi niño”. A propósito de un caso de Síndrome disejecutivo secundario a higroma bifrontal

“…Nuestro paciente presentó casi todos los efectos clínicos de las lesiones del lóbulo frontal: trastornos conductuales, acinesia, apatía, abulia, apraxia de la marcha, desinhibición de la conducta y agresividad; produciéndose cambios de la personalidad y la (4,5) conducta .…”

“…Se manifiesta como un comportamiento desinhibido, pueril, egocéntrico y a veces maníaco pareciéndose a un síndrome seudopsicopático. El síndrome medio basal o cingular produce alteraciones de la memoria emocional, en las tareas de supervisión atencional y (4,5) en la toma de decisiones .…”

Exosome release and cargo in Down syndrome

“…Into adolescence, frontal gray matter volume continues to be significantly smaller in those with DS (Hamner et al, ), providing a potential neuroanatomical basis for alterations in attention and working memory deficits in individuals with DS (Kirk et al, ; Naerland, Bakke, Storvik, Warner, & Howlin, ). In adults with DS, data suggest an early cortical degenerative process prior to the onset of an AD‐like phenotype, suggesting that cortical regions are highly vulnerable in DS (Fonseca, Yokomizo, Bottino, & Fuentes, ). The amyloid precursor protein gene ( APP ) is located on Chromosome 21 (Cooper et al, ), and individuals with DS exhibit accumulation of toxic amyloid peptides early in life (Prasher, Sajith, Mehta, Zigman, & Schupf, ), leading to aggregation of amyloid plaques in their third or fourth decade (Neale, Padilla, Fonseca, Holland, & Zaman, ; Rafii et al, ).…”