Visual contrast sensitivity in Alzheimer’s disease,mild cognitive impairment,and older adults with cognitive complaints

Deficits in contrast sensitivity (CS) have been reported in Alzheimer’s disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.     

Self- and informant reports of executive function on the BRIEF-A in MCI and older adults with cognitive complaints.

Amnestic mild cognitive impairment (MCI) is characterized by impaired episodic memory, although subtle executive problems have been noted on neuropsychological tests. Recent research also has described a group of healthy, non-depressed older adults with significant cognitive complaints (CC) but normal performance on neuropsychological testing. These individuals show structural and functional brain changes intermediate between those seen in MCI and healthy older adults without such complaints (HC). We evaluated executive functions in MCI and CC using the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), a newly developed self- and informant report questionnaire in 29 patients with amnestic MCI, 28 CCs, and 30 demographically matched HCs. MCI and CC participants reported significant difficulties with selective aspects of executive functioning relative to HCs despite clinically normal performance on neuropsychological tests of this cognitive domain. Scores were generally in the pattern of MCI>CC>HC, and findings were most pronounced for working memory. Additionally, MCI and CC participants were more likely than their informants to report clinically meaningful executive problems, though informants identified a similar pattern of difficulty overall. Results failed to reveal strong relations between the BRIEF-A and standardized neuropsychological tests of executive function. Overall findings indicate that the BRIEF-A is sensitive to subtle executive changes in MCI and CC and suggest the need for research to determine if executive complaints are predictive of clinical course.     

MCI patients’ EEGs show group differences between those who progress and those who do not progress to AD

The theta/gamma and alpha3/alpha2 ratio were investigated as early markers for prognosticating of progression to dementia. 76 subjects with mild cognitive impairment (MCI) underwent EEG recording, MRI scans and neuropsychological (NPS) tests. After 3 years of follow-up, three subgroups were characterized as converters to Alzheimer's disease (AD, N = 18), converters to non-AD dementia (N = 14) and non-converters (N = 44). The theta/gamma and alpha3/alpha2 ratio, performance on cognitive tests and hippocampal volume, as evaluated at the time of initial MCI diagnosis, were studied in the three groups. As expected, MCI to AD converters had the smallest mean hippocampal volume and poorest performance on verbal learning tests, whereas MCI to non-AD converters had poorest cognitive performance in non-verbal learning tests, abstract thinking, and letter fluency. Increased theta/gamma ratio was associated with conversion to both AD and non-AD dementia; increased alpha3/alpha2 ratio was only associated with conversion to AD.Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. EEG markers allow a mean correct percentage of correct classification up to 88.3%. Future prospective studies are needed to evaluate the sensitivity and specificity of these measures for predicting an AD outcome.     

Working memory and perseveration in verbal fluency

Letter and semantic fluency tasks are often used in neuropsychological assessment and are sensitive to many conditions. Performance is assessed by correct responses and errors, including perseverations. Healthy young adults performed letter and semantic fluency tasks. One group performed these tasks in the conventional manner; 2 other groups performed them while maintaining memory loads. The memory loads consisted either of words from the same category as the fluency task or of words from a different category. The results showed little effect of memory loads on correct responses but significant effects of memory load on perseveration rates: Same-category loads resulted in higher rates, especially in letter fluency. The results are discussed in terms of frontal lobe function in verbal fluency.     

Effects of mild and global cognitive impairment on the prevalence of fear of falling in community-dwelling older adults

Objectives

Few studies have reported the relationship between fear of falling (FoF) and mild and global cognitive impairment in community-dwelling older adults. We aimed to determine whether the status of cognitive impairment affects the prevalence of FoF in community-dwelling older adults.

Study design

Cross-sectional study among 4474 community-dwelling older adults who participated in the Obu Study of Health Promotion for the Elderly.

Main outcome measures

Participants underwent cognitive tests and were divided into three groups: cognitive healthy, mild cognitive impairment (MCI), and global cognitive impairment (GCI). FoF and related variables, such as fall history, physical function, and depression, were also investigated.

Results

The prevalence of FoF was significantly different by group (p < 0.001; healthy: 43.6%, MCI: 50.6%, GCI: 40.6%). Logistic regression analysis showed that GCI (odds ratio = 0.63; 95% confidence interval = 0.526–0.76) was independently associated with FoF, after controlling for confounding factors. Older adults with GCI showed the lowest prevalence of FoF, although they had the lowest physical function comparing with the other groups (p < 0.001).

Conclusion

MCI and GCI in community-dwelling older adults affect the prevalence of FoF in a completely different manner. Further study is required to determine whether insensitivity to FoF with GCI increases the risk of falling in older adults.     

Using verbal fluency to detect very mild dementia of the Alzheimer type

The study sample included 76 healthy older adults and 77 individuals with very mild dementia of the Alzheimer type (DAT). Semantic (animal) and letter (S and P) fluency tasks were used to examine quantitative (word generation) and qualitative (category clustering and switching) aspects of verbal fluency. The goal of the study was to evaluate the utility of fluency tasks in discriminating between healthy aging and very mild DAT. Our results indicated better performance for the healthy group than the DAT group in terms of number of words, number of clusters, number of switches, and size of clusters generated (an exception was clustering on letter S fluency). Clustering and switching variables were significantly correlated with number of words generated and therefore were not included in discriminant analysis. Discriminant analysis revealed that the combination of semantic fluency and narrative recall may be particularly useful in differentiating healthy aging from very mild DAT.     

Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints

The goal of the present study was to determine if there are global or regionally specific decreases in callosal area in early Alzheimer's disease (AD) and mild cognitive impairment (MCI). In addition, this study examined the corpus callosum of healthy older adults who have subjective cognitive complaints (CC) but perform within normal limits on neuropsychological tests. We used a semi-automated procedure to examine the total and regional areas of the corpus callosum in 22 patients with early AD, 28 patients with amnestic MCI, 28 healthy older adults with cognitive complaints, and 50 demographically matched healthy controls (HC). The AD, MCI, and CC groups all showed a significant reduction of the posterior region (isthmus and splenium) relative to healthy controls. The AD group also had a significantly smaller overall callosum than the controls. The demonstration of callosal atrophy in older adults with cognitive complaints suggests that callosal changes occur very early in the dementing process, and that these earliest changes may be too subtle for detection by neuropsychological assessments, including memory tests.     

Neuropsychological performance of a clinical sample of extremely obese individuals

Obesity is a leading cause of preventable death in America and its prevalence is increasing at an alarming rate. While it is known that individuals with specific obesity-related medical conditions perform poorly on neuropsychological tasks, recent evidence suggests that cognitive dysfunction in obese individuals may occur independently of medical co-morbidities. This study examined neuropsychological performance in a clinical sample of extremely obese patients. Individuals seeking surgical treatment of obesity (N = 68) were administered cognitive tests as part of a standard pre-surgical evaluation. Results indicated significant differences in performances of extremely obese individuals on tests of executive functioning (planning, problem solving, mental flexibility) in comparison to normative data. No significant differences emerged between obese patients with and without co-morbid medical conditions of hypertension, type II diabetes, and obstructive sleep apnea on the neuropsychological tasks specific to executive functioning. Taken together, these results provide further evidence of specific cognitive dysfunction in extremely obese individuals.     

Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer's disease

In the present work, we investigated the level of IgM autoantibodies directed against different Aβ epitopes as potential diagnostic biomarker for Alzheimer's disease (AD). Anti-Aβ autoantibody levels were measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To validate the presence of anti-Aβ IgMs, pooled plasma samples were subjected to gel-filtration analysis. The mean level of pGluAβ-IgM (N-terminal truncated starting at position three with pyroglutamate) was significantly decreased in AD patients as compared to HC. In the group of MCI patients there was a significant positive correlation between pGluAβ-IgM and cognitive decline analyzed by MMSE (rho = 0.58, d.f. = 13, p = 0.022). These observations indicate that the level of IgM autoantibodies against pGluAβ is a promising plasma biomarker for AD and correlates with the cognitive status of individuals at risk to develop AD.     

Clustering and switching on verbal and figural fluency functions in adults with attention deficit hyperactivity disorder

Introduction. Neuropsychological studies of adult patients with ADHD have revealed marked disturbances of executive functions including impairments of attention, working memory, impulsivity, shifting, and divergent thinking. Phonemic fluency tasks, in particular, have been shown to be sensitive measures for the assessment of executive functions of adults with ADHD.Methods. The present study has examined figural fluency and both phonemic and semantic verbal fluency in 34 adult patients with ADHD and 34 healthy participants. For evaluation of fluency performance the number of words or designs, the number of repetitions and the number of deviations from test rules were calculated. Furthermore, clustering strategies and switching responses were analysed. In comparison with healthy participants, patients with ADHD produced significantly fewer words or designs, but they did not differ from healthy participants in the number of repetitions or rule violations.Results. Analysis of switching and clustering showed that patients produced significantly fewer switching responses on both verbal fluency tasks, although patients tended to generate smaller clusters. Switching on the figural fluency task was unimpaired.Conclusions. The results of the present study suggest that adult patients with ADHD may suffer from a dysfunction that may affect retrieval processes and the categorisation of knowledge.     

Elevated perseveration errors on a verbal fluency task in frequent nightmare recallers: a replication

A recent study reported that individuals recalling frequent idiopathic nightmares (NM) produced more perseveration errors on a verbal fluency task than did control participants (CTL), while not differing in overall verbal fluency. Elevated scores on perseveration errors, an index of executive dysfunction, suggest a cognitive inhibitory control deficit in NM participants. The present study sought to replicate these results using a French‐speaking cohort and French language verbal fluency tasks. A phonetic verbal fluency task using three stimulus letters (P, R, V) and a semantic verbal fluency task using two stimulus categories (female and male French first names) were administered to 23 participants with frequent recall of NM (≥2 NM per week, mean age = 24.4 ± 4.0 years), and to 16 CTL participants with few recalled NM (≤ 1 NM per month, mean age = 24.5 ± 3.8 years). All participants were French‐speaking since birth and self‐declared to be in good mental and physical health apart from their NM. As expected, groups did not differ in overall verbal fluency, i.e. total number of correct words produced in response to stimulus letters or categories (P = 0.97). Furthermore, groups exhibited a difference in fluency perseveration errors, with the NM group having higher perseveration than the CTL group (P = 0.03, Cohen's d = 0.745). This replication suggests that frequent NM recallers have executive inhibitory dysfunction during a cognitive association task and supports a neurocognitive model which posits fronto‐limbic impairment as a neural correlate of disturbed dreaming.     

The positive symptoms of acute schizophrenia and latent inhibition in humans and animals: Underpinned by the same process(es)?

Introduction. Semantic memory impairments in schizophrenia have been reported across a wide range of neuropsychological tests. Set against a backdrop of fairly widespread cognitive impairments, it is difficult to know whether there is a primary, or secondary, impairment of semantic memory in schizophrenia. Also, whether there is a profile of differential impairment across the range of neuropsychological tests.

Methods. Employing a systematic search strategy, 91 papers were identified which have assessed participants with schizophrenia on a measure of semantic memory. A series of meta-analyses were then conducted which provided combined weighted means for performance on tasks of naming, word–picture matching, verbal fluency, priming, and categorisation.

Results. An uneven profile of impairment is reported with large effect sizes for tests of naming and verbal fluency, medium effect sizes for word–picture matching and association and small effect sizes for categorisation and priming tests.

Conclusions. This uneven profile supports the claim that a degradation of semantic knowledge may not be adequate in explaining the semantic memory impairment in schizophrenia. This conclusion is supported by the data which report a relationship between an executive dysfunction and poor priming and fluency performance particularly. The data support a link between Formal Thought Disorder and semantic memory impairments on tests of naming and verbal fluency but on other tests evidence is equivocal.     

A meta-analytic review of verbal fluency deficits in schizophrenia relative to other neurocognitive deficits

Introduction. A prominent view in the neuropsychological literature is that schizophrenia is particularly associated with executive dysfunction, yet in a meta-analytic review it was concluded that, relative to their general level of intellectual functioning, schizophrenics are not disproportionately impaired on a measure of this construct, the Wisconsin Card Sorting Test (WCST). However, verbal fluency tests may be more valid measures of executive functioning as they are more sensitive to the presence of focal frontal lobe injuries.Method. A meta-analysis was conducted on 84 studies comparing the performance of schizophrenics and healthy controls on tests of phonemic and semantic fluency, as well as other cognitive measures presumed to impose only minimal demands on executive functioning.Results. Neither phonemic or semantic fluency deficits qualified as differential deficits relative to general intelligence or psychomotor speed. Patients with schizophrenia were significantly more impaired on semantic relative to phonemic fluency.Conclusions. As for the WCST, deficits on tests of verbal fluency reflect a more generalised intellectual impairment and not particular difficulties with executive control processes. The larger deficit for semantic relative to phonemic fluency suggests that, in addition to general retrieval difficulties, schizophrenia is associated with compromises to the semantic store.     

Subjective cognitive decline predicts future deterioration in cognitively normal patients with Parkinson's disease

Increasing evidence suggests that subjective cognitive decline (SCD) is a potential predictor of future cognitive decline or dementia. We investigated whether SCD in patients with Parkinson's disease (PD) is a predictor of future cognitive decline. Forty-six cognitively normal patients with PD were selected using comprehensive neuropsychological tests, and classified depending on the presence (PD-SCD⁺, n = 25) or absence of SCD (PD-SCD⁻, n = 21). After a mean follow-up of 2.4 years, we repeated the cognitive assessments with the same subjects. The clinical characteristics and cognitive performance of the 2 groups did not differ at baseline. At the follow-up assessment, 11 patients in the PD-SCD⁺ group (44.0%) and 2 in the PD-SCD⁻ group (9.5%) were diagnosed with mild cognitive impairment (MCI), and the PD-SCD⁺ patients showed more rapid decline in semantic fluency and visuospatial memory tasks than those in the PD-SCD⁻ group. A multivariate logistic regression analysis showed that presence of SCD (odds ratio, 8.378; 95% confidential interval, 1.472–47.683, p = 0.017) and higher Unified PD Rating Scale motor score of 20 or more (odds ratio, 4.539; 95% confidential interval, 1.004–20.528; p = 0.049) were risk factors for incident MCI. Present results demonstrate that SCD in cognitively normal patients with PD is an independent risk factor for incident MCI and acts as a predictor for future cognitive decline.     

40-Hz steady state response in Alzheimer's disease and mild cognitive impairment

The 40-Hz steady state response (SSR) reflects early sensory processing and can be measured with electroencephalography (EEG). The current study compared the 40-Hz SSR in groups consisting of mild Alzheimer's disease patients (AD) (n = 15), subjects with mild cognitive impairment (MCI) (n = 20) and healthy elderly control subjects (n = 20). All participants were naïve for psychoactive drugs. Auditory click trains at a frequency of 40-Hz evoked the 40-Hz SSR. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment 1 week after the first. The results showed a high TRR and a significant increase of 40-Hz SSR power in the AD group compared to MCI and controls. Furthermore a moderate correlation between 40-Hz SSR power and cognitive performance as measured by ADAS-cog was shown.The results suggest that 40-Hz SSR might be an interesting candidate marker of disease progression.     

Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity

Telomere length (TL), a measure of replicative senescence, decreases with aging, but the factors involved are incompletely understood. To determine if age-associated reductions in TL are related to habitual endurance exercise and maximal aerobic exercise capacity (maximal oxygen consumption, VO₂max), we studied groups of young (18-32 years; n = 15, 7 male) and older (55-72 years; n = 15, 9 male) sedentary and young (n = 10, 7 male) and older (n = 17, 11 male) endurance exercise-trained healthy adults. Leukocyte TL (LTL) was shorter in the older (7059 ± 141 bp) vs. young (8407 ± 218) sedentary adults (P < 0.01). LTL of the older endurance-trained adults (7992 ± 169 bp) was ∼900 bp greater than their sedentary peers (P < 0.01) and was not significantly different (P = 0.12) from young exercise-trained adults (8579 ± 413). LTL was positively related to VO₂max as a result of a significant association in older adults (r = 0.44, P < 0.01). Stepwise multiple regression analysis revealed that VO₂max was the only independent predictor of LTL in the overall group. Our results indicate that LTL is preserved in healthy older adults who perform vigorous aerobic exercise and is positively related to maximal aerobic exercise capacity. This may represent a novel molecular mechanism underlying the “anti-aging” effects of maintaining high aerobic fitness.     

Early event-related potentials changes during simple mental calculation in Chinese older adults with mild cognitive impairment: A case–control study

The aim was to examine early event-related potential (ERP) changes during mental arithmetic calculation task in mild cognitive impairment patients compared to healthy elderly. 16 mild cognitive impairment (MCI) subjects and 16 healthy Chinese older adults were studied. Event-related potentials were elicited using a simple mental calculation task. Performance on arithmetic calculation task, and the latency and amplitude of early event-related potential components (N1, P1, N170, and P2) were compared between the two groups. The reaction time of MCI group was significantly longer than that of control group (1691.03 ± 94.59 vs. 1539.55 ± 27.76, P < 0.01). The correct rate of MCI group (0.9463 ± 0.04) was significantly lower than that of control group (0.9776 ± 0.02, P < 0.01). The latency of temporal–occipital N170 and central–prefrontal P2 of MCI group were significantly prolonged compared to controls. MCI subjects presented significantly higher P2 amplitude. Compared with healthy controls, N170 was significantly lower at left temporal–occipital region and higher at right temporal–occipital region in mild cognitive impairment. Mild cognitive impairment patients had deficit on simple calculation. The early arithmetic calculation processing mechanism of mild cognitive impairment patients may be different from normal people.     

A randomized controlled trial of estrogen treatment in men with mild cognitive impairment

This randomized, placebo-controlled, cross-over study investigated whether estrogen treatment would have a beneficial effect on tests of verbal memory in men with mild cognitive impairment (MCI). Forty-three men newly diagnosed with MCI were administered a battery of neuropsychological tests before randomly receiving 12 weeks of treatment with estrogen or placebo followed by a 12 week cross-over treatment. A significant improvement in the total score, and in two subscale scores of the Buschke Selective Reminding Test occurred following estrogen treatment compared to both pretreatment and post-placebo scores (p < 0.05). However, benefit occurred only in the men who had received estrogen for 12 weeks following 12 weeks of placebo. Although these findings tentatively suggest that treatment with estrogen may improve verbal memory in men with MCI, the fact that the improvement occurred only in the group that received estrogen following 12 weeks of placebo and the absence of improvement on every test of verbal memory administered suggests that these findings need to be replicated using a larger sample size.     

Apolipoprotein E modulates auditory event-related potentials in healthy aging

42 individuals ranging from 47 to 73 years of age underwent an auditory three-stimulus oddball task while their event-related potentials (ERPs) were recorded. Half were APOE ?3 homozygotes and the remaining participants were either ?3/?4 heterozygotes (n = 13), or ?4 homozygotes (n = 8). Analyses of variance showed that the heterozygotes had lower N1 amplitudes than the ?3 homozygotes, consistent with a previous study of participants with mild cognitive impairment (MCI) [I. Reinvang, T. Espeseth, L. Gjerstad, Cognitive ERPs are related to ApoE allelic variation in mildly cognitively impaired patients, Neuroscience Letters 382 (3) (2005) 346–351]. APOE genotype also significantly modulated N2 latency. ?4 homozygotes had longer N2 latencies, and importantly, longer N2 latencies predicted decline in verbal learning after 3.5 years follow up. These findings indicate a potential clinical significance of individual differences in ERP components N1 and N2.     

Associations between sleep duration and cognitive impairment in mild cognitive impairment

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. A subsample of 271 participants with a diagnosis of probable Alzheimer's disease (AD; N = 50) or mild cognitive impairment (MCI; N = 121) and 100 persons who were not cognitively impaired (NI) were recruited from a large population‐based cohort in the island of Crete, Greece (3140 older adults aged >60 years). All participants underwent extensive neuropsychiatric/neuropsychological evaluation and a 3‐day 24‐hr actigraphy. Objective sleep variables and their association with neuropsychological performance were examined across the three groups, controlling for demographics, body mass index, depression, sleep apnea symptoms and psychotropic medications. Patients with AD had significantly longer 24‐hr total sleep time (TST) compared to the MCI and NI groups. Long 24‐hr TST was associated with reduced performance on tasks that placed significant demands on attention and processing speed in the MCI group and the AD group. Elderly patients with MCI have similar objective sleep duration to normal controls, whereas AD patients sleep longer. Long sleep duration in patients with multidomain subtypes of MCI is associated with critical non‐memory cognitive domains. It appears that within the MCI group those that sleep longer have more severe cognitive impairment.