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Cognitive activity, education and socioeconomic status as preventive factors for mild cognitive impairment and Alzheimer's disease

Growing epidemiological evidence suggests that premorbid participation in cognitive leisure activities (CLA) reduces the risk of dementia by increasing cognitive reserve. We investigated the differential effect of CLA, education, and socioeconomic status (SES) on the development of mild cognitive impairment (MCI) and Alzheimers disease (AD). Participants in the prospective population-based ILSE study (*1930-1932; 12-year follow-up) were examined in three examination waves (t1:1993/94; t2:1997/98; t3:2005/07). In total, 381 subjects of the original cohort (n=500) were re-examined at t3. Of these subjects 29% received the diagnosis of MCI and 7% of AD. Subjects participated in a thorough psychogeriatric examination and neuropsychological testing. Moreover, they took part in a detailed autobiographical interview and completed questionnaires including socio-demographic data and current frequency of participation in CLA. Subjects who were highly cognitively active at t1 had a significantly reduced risk of developing MCI/AD at t3 (scores adjusted for education, SES, gender, and depressive symptoms). Additionally, high education and high SES separately reduced the risk of MCI and AD. Our results confirm the hypothesis that a high level of CLA acts as a protective factor against the development of MCI and AD by increasing cognitive reserve. This effect is not accounted for by important potential confounders.

Reduced olfactory bulb and tract volume in early Alzheimer's disease—A MRI study

Olfactory dysfunction has been reported to occur already in the early stages of Alzheimers disease (AD) and to increase with disease severity. In neuropathological research, the deposition of neurofibrillary tangles and neuritic plaques in the olfactory bulb and tract (OBT) of AD patients has been consistently demonstrated. We used high-resolution magnetic resonance imaging (MRI) to determine the volume of the OBT in 21 patients with early AD and in 21 healthy comparison subjects. The OBT was manually traced on consecutive coronal slices. When compared to healthy controls, right, left and mean OBT volumes were significantly reduced in patients with AD (p<0.01). In AD patients, the mean OBT volume was significantly correlated with global cognitive performance as determined by the mini-mental state examination (r=0.605; p=0.004). Manual tracing on MRI images revealed OBT atrophy to be present early in the course of AD. Since the respective findings were associated with cognitive impairment, they may contribute to early recognition and diagnosis of the disease.

Type II Diabetes in Mild Cognitive Impairment and Alzheimer's Disease: Results from a Prospective Population-Based Study in Germany

Diabetes mellitus type 2 (T2DM) is considered to be an important risk factor for mild cognitive impairment (MCI) and subsequent Alzheimers disease (AD). The majority of studies relating T2DM to MCI and AD were performed in North America. We investigated the potential impact of T2DM on the development of MCI and AD in the Interdisciplinary Longitudinal Study on Adult Development and Aging which involves a representative birth cohort of subjects born between 1930 and 1932 in Germany. Subjects received a thorough psycho-geriatric examination and neuropsychological testing; particular care was taken to exclude subjects with severe medical or neurological conditions sufficient to explain the cognitive deficits, or other major psychiatric disorders. When compared to healthy subjects (n=159), patients with MCI (n=108) or AD (n=26) showed a tendency towards increased prevalence rates for T2DM (17% vs. 23%; chi2=1.7, p=0.18). In both patients with MCI and controls, T2DM was associated with psychomotor slowing but not deficits in other cognitive domains typically involved in MCI. Our findings indicate that T2DM is involved in MCI and may aggravate the clinical picture as a concomitant factor.

MRI-Derived Atrophy of the Olfactory Bulb and Tract in Mild Cognitive Impairment and Alzheimer's Disease

There is increasing histopathological evidence that the olfactory bulb and tract (OBT) is a primary focus of neurodegenerative changes in Alzheimers disease (AD). Correspondingly, high-resolution magnetic resonance imaging revealed significant atrophy of the OBT in manifest AD. Whether these alterations are already present in mild cognitive impairment, the assumed preclinical stage of AD, has not been investigated yet. OBT volumes were assessed by manual tracing in 29 patients with mild cognitive impairment, 27 patients with probable AD, and 30 healthy controls. In a second step, voxel based morphometry was used to investigate the potential association between OBT atrophy and morphological changes in other brain regions. Patients had significantly lower OBT volumes when compared to controls, with atrophy being most prominent in the AD group. In addition, OBT atrophy was associated with a decreased medial temporal lobe (MTL) gray matter density bilaterally. Our findings indicate that neurodegeneration in OBT and MTL regions is linked and suggest that OBT volume might be a surrogate marker in AD.

Clock drawing performance and brain morphology in mild cognitive impairment and Alzheimer’s disease

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimers disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region.

Physical fitness as a protective factor for cognitive impairment in a prospective population-based study in Germany.

To evaluate the predictive effects of subjective measures of physical activity (PA) and objective measures of physical fitness (PF) on dementia risk, Participants of the prospective population-based ILSE-study (*1930-1932; 12-year follow-up) were examined at three examination waves (t1 : 1993/94; t2 : 1997/98; t3 : 2005/07). 381 subjects of the original cohort (n = 500) were re-examined at t3. 29% of the subjects who were cognitively healthy at baseline received the diagnosis of mild cognitive impairment (MCI) and 7% of Alzheimers disease (AD). Subjects were screened for physical and mental health using medical interviews, physical, and neuropsychological examinations. Participants completed a questionnaire on their current and past PA at t1. Subjects were classified as physically active if they reported a regular sport activity for at least 2 hours per week in the past year. Muscular strength (handgrip) and motor coordination (balance) served as objective indicators of PF. Subjects who passed the balance-test at t1 had a reduced risk of developing MCI/AD at t3 (OR = 0.35, 95%CI 0.19-0.66, p < 0.01) and performed significantly better on various neuropsychological measures. Muscular strength or subjective reports of PA did not predict MCI/AD development. Our results confirm the hypothesis that PF acts as a protective factor for the development of cognitive disorders. In our study, context, motor coordination served as a better predictor than muscular strength or self-rated PA. Since subjects with cognitive disorders due to cerebral and/or systemic disorders were excluded from the analyses, our findings suggest that the effect of skill-related PF extends beyond the reduction of cardiovascular risk factors.

Premorbid Personality Traits and Their Course in Mild Cognitive Impairment: Results from a Prospective Population-Based Study in Germany

Background: Personality traits contribute to cognitive functioning. We present a study comparing personality traits in normal ageing and mild cognitive impairment (MCI). Methods: We conducted a representative longitudinal study including 222 subjects from a cohort born between 1930 and 1932 (n = 500) examined at three examination waves (t1: 1993/1994; t2: 1997/1998; t3: 2005/2007). Personality traits were assessed with the NEO-Five-Factor Inventory questionnaire. Results: Healthy controls and patients with MCI showed a significant (p < 0.05) decrease concerning their levels of neuroticism and extraversion over time. MCI subjects scored significantly higher on neuroticism at baseline and lower on openness at all examinations compared to healthy controls. Subjects with higher baseline neuroticism showed a 2.24 times higher risk of developing MCI at the third follow-up (odds ratio = 2.24, 95% confidence interval = 1.12–4.45 – scores adjusted for education and sex). Conclusions: MCI subjects differ in their premorbid personality traits compared to healthy controls. According to our study, higher neuroticism should be considered a risk factor for the development of MCI.

High contextual sensitivity of metaphorical expressions and gesture blending: A video event-related potential design

Human communication in a natural context implies the dynamic coordination of contextual clues, paralinguistic information and literal as well as figurative language use. In the present study we constructed a paradigm with four types of video clips: literal and metaphorical expressions accompanied by congruent and incongruent gesture actions. Participants were instructed to classify the gesture accompanying the expression as congruent or incongruent by pressing two different keys while electrophysiological activity was being recorded. We compared behavioral measures and event related potential (ERP) differences triggered by the gesture stroke onset. Accuracy data showed that incongruent metaphorical expressions were more difficult to classify. Reaction times were modulated by incongruent gestures, by metaphorical expressions and by a gesture-expression interaction. No behavioral differences were found between the literal and metaphorical expressions when the gesture was congruent. N400-like and LPC-like (late positive complex) components from metaphorical expressions produced greater negativity. The N400-like modulation of metaphorical expressions showed a greater difference between congruent and incongruent categories over the left anterior region, compared with the literal expressions. More importantly, the literal congruent as well as the metaphorical congruent categories did not show any difference. Accuracy, reaction times and ERPs provide convergent support for a greater contextual sensitivity of the metaphorical expressions.

Apolipoprotein E polymorphism and brain morphology in mild cognitive impairment.

Background: The apolipoprotein E (ApoE) genotype has been confirmed as the major genetic risk factor for late-onset Alzheimer’s disease (AD). How the ApoE genotype and brain morphology relate to each other is only partly understood, particularly in mild cognitive impairment, the assumed prestage of AD. Methods: A total of 83 subjects with mild cognitive impairment (aging-associated cognitive decline criteria) were investigated with optimized voxel-based morphometry (VBM). We tested for differences in gray and white matter densities between groups according to their ApoE status, i.e. Ε4 allele noncarriers (n = 42), subjects with one Ε4 allele (n = 27) and subjects with two Ε4 alleles (n = 14). Results: In individuals carrying two Ε4 alleles, VBM revealed a decline in gray matter density predominantly in the medial temporal lobe region. Subjects with a single copy of the Ε4 allele exhibited gray matter atrophy in the right inferior frontal gyrus. With respect to white matter changes, atrophy was only found in subjects homozygous for Ε4 and confined to the right superior and middle temporal gyrus. Conclusion: Our findings support the hypothesis that the ApoE genotype in mild cognitive impairment might be associated with structural changes typically found in the early stages of AD.

Episodic autobiographical memory in normal aging and mild cognitive impairment: A population-based study

While episodic memory impairment has been extensively studied in normal and pathological aging, studies investigating age-related episodic autobiographical memory among representative samples are scarce. We therefore investigated episodic autobiographical memory in a sample of 395 participants of a population-based prospective study of aging. Three groups were compared, consisting of 194 middle-aged participants, 138 healthy old-aged participants and 63 patients with mild cognitive impairment (MCI). Results showed a significant impairment of episodic autobiographical memory performance associated with MCI, but not with normal aging. These deficits were significantly correlated with verbal memory performances, but not with measures of executive functions.