Mild cognitive impairment in dementia with Lewy bodies: an update and outlook

Dementia with Lewy bodies (DLB), the second most common degenerative neurocognitive disorder after Alzheimer disease (AD), is frequently preceded by a period of mild cognitive impairment (MCI), in which cognitive decline is associated with impairment of executive functions/attention, visuospatial deficits, or other cognitive domains and a variety of noncognitive and neuropsychiatric symptoms, many of which are similar but less severe than in prodromal AD. While 36-38% remain in the MCI state, at least the same will convert to dementia. Biomarkers are slowing of the EEG rhythms, atrophy of hippocampus and nucleus basalis of Meynert, temporoparietal hypoperfusion, signs of degeneration of the nigrostriatal dopaminergic, cholinergic and other neurotransmitter systems, and inflammation. Functional neuroimaging studies revealed disturbed connectivity of frontal and limbic networks associated with attention and cognitive controls, dopaminergic and cholinergic circuits manifested prior to overt brain atrophy. Sparse neuropathological data showed varying Lewy body and AD-related stages associated with atrophy of entorhinal, hippocampal, and mediotemporal cortices. Putative pathomechanisms of MCI are degeneration of limbic, dopaminergic, and cholinergic systems with Lewy pathology affecting specific neuroanatomical pathways associated with progressing AD-related lesions, but many pathobiological mechanisms involved in the development of MCI in LBD remain to be elucidated as a basis for early diagnosis and future adequate treatment modalities to prevent progression of this debilitating disorder.