Episodic memory and speed/attention deficits are associated with Alzheimer-typical CSF abnormalities in MCI

Abstract

Mild cognitive impairment (MCI) is regarded as the prodromal stage of dementia disorders, such as Alzheimer's disease (AD).Objective: To compare the neuropsychological profiles of MCI subjects with normal concentrations of total tau (T-t) and Ab42 in CSF (MCI-norm) to MCI subjects with deviating concentrations of the biomarkers (MCI-dev). MCI-norm (N 5 73) and MCI-dev (N 5 73) subjects were compared to normal controls (N 5 50) on tests of speed0attention, memory, visuospatial function, language and executive function.Results: MCI-norm performed overall better than MCI-dev, specifically on tests of speed and attention and episodic memory. When MCI-dev subjects were subclassified into those with only high T-tau (MCI-tau), only low Ab42 (MCI-Ab) and both high T-tau and low Ab42 (MCI-tauAb), MCI-tauAb tended to perform slightly worse. MCI-tau and MCI-Ab performed quite similarly.Conclusions: Considering the neuropsychological differences, many MCI-norm probably had more benign forms of MCI, or early non-AD forms of neurodegenerative disorders. Although most MCI-dev performed clearly worse than MCI-norm on the neuropsychological battery, some did not show any deficits when compared to age norms. A combination of CSF analyses and neuropsychology could be a step toward a more exact diagnosis of MCI as prodromal AD. (JINS, 2008, 14, 582-590.)

Mild cognitive impairment (part 2): biological markers for diagnosis and prediction of dementia in Alzheimer's disease

“…8 The main component of NP is aggregated and insoluble b-amyloid 42 , whereas NFTs are the result of hyperphosphorylation of Tau protein in neurons. 9 Current models for the pathophysiology of AD are based on the bamyloid hypothesis.…”

“…15 These biomarkers reflect core neuropathological (and presumably pathophysiological) features of AD, 21 and have been validated in postmortem studies. [22][23][24] The typical pattern for these CSF biomarkers in AD patients is commonly referred to as the AD signature in the CSF, i.e., low concentrations of Ab 42 and high concentrations of T-Tau and P-Tau. These findings reflect, respectively, the sinking and deposition of Ab 42 in plaques (in detriment of its clearance through the CSF) and axonal dysfunction leading to neuronal degeneration.…”

“…[22][23][24] The typical pattern for these CSF biomarkers in AD patients is commonly referred to as the AD signature in the CSF, i.e., low concentrations of Ab 42 and high concentrations of T-Tau and P-Tau. These findings reflect, respectively, the sinking and deposition of Ab 42 in plaques (in detriment of its clearance through the CSF) and axonal dysfunction leading to neuronal degeneration. The latter marker is perhaps specifically associated with AD, given the central role of P-Tau in the formation of paired helical filaments (PHFs) and NFTs.…”

“…These studies suggest that the AD signature may help predict the incidence of memory deficits, i.e., amnestic MCI. 40,41 More recently, abnormalities in CSF biomarkers have been correlated with poorer performance in memory and attention tasks 42 and with worse functional performance in the instrumental abilities of daily living, 43 both in cognitively healthy subjects and in those with MCI. In addition, studies of healthy elderly subjects showed that lower CSF Ab 42 levels predicted the emergence of SMC up to 3 years of follow-up.…”

“…In particular, concentrations of Ab 40 and Ab 42 (in addition to the Ab 42/40 ratio) have been extensively analyzed in clinical and epidemiological studies. A significant increase in plasma levels of Ab 40 , along with a decrease in Ab 42 (and in the Ab 42/40 ratio), has been reported to predict cognitive decline in MCI patients and healthy elders. 48,49 Increments in plasma Ab 42 have also been reported to predict AD in these subjects.…”