STOCKHOLM – Preliminary results of the ongoing European Alzheimer's Disease Consortium's DESCRIPA study are pointing the way toward clinical criteria that may help single out which types of mild cognitive impairment lead to Alzheimer's disease, speakers reported at the 12th Congress of the International Psychogeriatric Association.
Twenty-five centers conducted DESCRIPA (Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease), a prospective cohort study that included 850 patients with suspected mild cognitive impairment (MCI). Presentations at the congress involved data on various subsets of the 850 patients.
The study investigators had no predefined criteria for MCI but included patients who were aged 55 years or older and had received consecutive referrals for cognitive impairment. They excluded patients who had a diagnosis of dementia at baseline and obvious causes of cognitive impairment such as stroke and depression. Based on neuropsychologic testing, patients were divided into four MCI subtypes: subjective complaints (no impairments on cognitive testing), nonamnestic (impairments on fluency, trail making, or single-institution tests), amnestic single domain (impairment on a word recall test), and amnestic multiple domain (impairment on word recall and at least one other memory test).
Impact of Apo E Genotype
The frequency of the ϵ4 allele of the apolipoprotein E gene (apo E) varies significantly with specific MCI subtypes and between regions of Europe but does not have strong enough predictive value alone to distinguish among MCI subtypes, according to Caroline Graff, M.D., Ph.D., of the Karolinska University Hospital, Huddinge, Sweden.
The distribution of ϵ4 allele frequency and the average age of patients differed significantly among the four MCI subtypes in a group of 386 patients at 11 centers who were genotyped for apo E allele status. The frequency of the ϵ4 allele increased from 17% of nonamnestic patients to 21% of those with subjective MCI, 30% of amnestic multiple domain, and 32% of amnestic single domain. Age varied from 66 years in subjective MCI to 72 years in amnestic single-domain patients. The differences were still significant when the four subtypes were collapsed into a nonamnestic group composed of the subjective and nonamnestic MCI patients (19%, 68 years) and an amnestic group composed of the amnestic single- and multiple-domain groups (31%, 72 years).
The distribution of MCI subtypes and age was significantly different among the centers. Frequency of the ϵ4 allele also varied according to the centers' location in Europe. The average frequency was lowest (8%) in Thessaloniki, Greece, and highest (33%) in Bath, England.
The variables of center, age, and apo E genotype were significantly associated with MCI subtype in a multivariate logistic regression analysis. The effect of center was the strongest predictor of MCI subtype, and it could not be explained by the effect of age or apo E status alone. “There is something else inherent in center,” Dr. Graff said.
If one hypothesizes that the different MCI subtypes predict the type of dementia that a person will develop, this could mean that the prevalence of the different types of dementia differ among these countries, she pointed out.
EEG Abnormalities in Amnestic Subtype
Decline in the function of posterior cortical regions of the brain such as the temporal, occipital, and parietal lobes characterize the resting EEG of patients with amnestic MCI, Flavio Nobili, M.D., reported at the congress.
In a preliminary analysis, the temporal, occipital and parietal cortical regions of the brain in 96 patients who had digital EEG performed at five centers had significant reductions in α-1 frequency, compared with the same regions in 55 control patients matched for age, sex, and education. This result is “consistent with the hypothesis of a transition stage between amnestic MCI and Alzheimer's disease,” said Dr. Nobili of the department of clinical neurophysiology at the University of Genoa (Italy).
Other studies of resting EEG in MCI patients have shown decreases in α frequency. It's known that deafferentation of thalamo-cortical and cortico-cortical brain connections and deficits in neurotransmission underlie the slowing down of EEG readings in Alzheimer's disease (AD) patients. Even in early stages of AD, EEG readings typically show decreases in α frequency and a shift to a lower α peak frequency.
A follow-up study will be necessary to determine the influence that the heterogeneity of the amnestic MCI population has on these results since the distribution of EEG power in defined, early-stage AD also is very heterogeneic, he noted.
Importance of Noncognitive Symptoms
Noncognitive symptoms are common in MCI patients but do not appear to occur at significantly different rates in MCI subtypes, according to a preliminary study of 324 patients with full Neuropsychiatric Inventory (NPI) scores.