Neuropathological studies suggest that the basal forebrain cholinergic system (BFCS) is affected in Alzheimer's disease (AD), but there is no in vivo evidence of early damage to this system in subjects at high risk of developing AD. Here, we found that mild cognitive impairment (MCI) patients exhibited significant volume reduction of the nucleus basalis of Meynert (NbM) using recently developed probabilistic maps of the BFCS space. In addition, volumes of different magnocellular compartments varied significantly with regional gray matter atrophy in regions known to be affected by AD and were found to correlate with cognitive decline in MCI patients. Bilateral reductions of the horizontal nucleus of the diagonal band of Broca (Ch3) and frontal lobe (medial frontal, orbital, subcallosal gyrus, anterior cingulate, and middle frontal gyrus) were significantly associated with a global decline in cognitive status, whereas volume reduction of the posterior compartment of Ch4 (NbM) and temporal lobe (including hippocampus, entorhinal cortex, and amygdala) were associated with impaired delayed recall in MCI patients. These findings establish, for the first time, a link between degeneration of specific cholinergic compartments of the BFCS and cognitive-related deficits in subjects at high risk of developing AD.

Objective: To determine the frequency, associated factors and outcome of dementia previous to a stroke. Design: Cross-sectional study of a cohort of 324 consecutive unselected stroke patients (mean age 70.9 years, range 20–98; 255 ischaemic, 46 haemorrhagic and 25 indefinite). Methods: Cognitive and functional status prior to stroke were assessed by means of an interview to a relative, a short version of the Informant Questionnaire on Cognitive Decline in the Elderly and the Barthel Index. The DSM-III-R criteria were used to establish the diagnosis of prestroke dementia. Clinical and CT features of patients with and without prestroke dementia were compared. Results: Forty-nine patients (15%) were demented before stroke; they were significantly older, less well educated, they had more frequently female gender, prior cerebrovascular disease, cerebral and medial temporal lobe atrophy and leukoaraiosis in the CT scan, and they had a higher mortality rate. Female sex (OR 3.7, CI 95% 1.2–12), low education (OR 2.1, CI 95% 1.1–4.2), previous stroke (OR 3.6, CI 95% 1.2–11), and cerebral atrophy (OR 3.8, CI 95% 1.7–8.3) were independently associated with prestroke dementia in the logistic regression analysis. Conclusions: Fifteen percent of stroke patients have prestroke dementia and they have a worse outcome. Factors associated with prestroke dementia are reminiscent both of degenerative and vascular brain pathology.

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Resonance in thalamocortical networks is critically involved in sculpting oscillatory behavior in large ensembles of neocortical cells. Neocortical oscillations provide critical information about the integrity of thalamocortical circuits and functional connectivity of cortical networks, which seem to be significantly disrupted by the neuronal death and synapse loss characterizing Alzheimer's disease (AD). By applying a novel analysis methodology to overcome volume conduction effects between scalp electroencephalographic (EEG) measurements, we were able to estimate the temporal activation of EEG‐alpha sources in the thalamus and parieto‐occipital regions of the cortex. We found that synaptic flow underlying the lower alpha band (7.5–10 Hz) was abnormally facilitated in patients with mild cognitive impairment (MCI) as compared to healthy elderly individuals, particularly from thalamus to cortex (∼38% higher). In addition, the thalamic generator of lower alpha oscillations was also abnormally activated in patients with MCI. Regarding the upper alpha subdivision (10.1–12.5 Hz), both controls and patients with MCI showed a bidirectional decrease of thalamocortical synaptic transmission, which was age‐dependent only in the control group. Altogether, our results suggest that functional dynamics of thalamocortical networks differentiate individuals at high risk of developing AD from healthy elderly subjects, supporting the hypothesis that neurodegeneration mechanisms are active years before the patient is clinically diagnosed with dementia. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

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