Blog Archives

Volumes of Lateral Temporal and Parietal Structures Distinguish Between Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

Distinguishing amnestic mild cognitive impairment (MCI) from Alzheimer’s disease (AD) and healthy aging depends mainly on clinical evaluation, and, ultimately, on investigator’s judgment. Clinical evaluation in vivo is based primarily on cognitive assessments. The present study explores the potential of volumetric magnetic resonance imaging of parietal and lateral temporal brain structures to support the diagnosis of AD and to distinguish AD patients from patients with MCI and healthy control subjects (HCS). 52 age-matched HCS, 18 patients with MCI, and 59 patients with probable late onset AD were investigated. Using computational, neuromorphometric procedures gray matter (GM) was automatically parcellated into 28 local regions of interest, the volumes of which were computed. The left hippocampus (sensitivity/specificity: 80.8–90.4%/55.6–86.4%) and the right hippocampus (73.1–90.4%/66.7–84.7%) provided highest diagnostic accuracy in separating all three diagnostic groups. Promising diagnostic values for distinguishing MCI from HCS were found for the left superior parietal gyrus (61.5%/55.6%) and left supramarginal gyrus (65.4%/66.7%), and for distinguishing subjects with MCI from AD patients for the right middle temporal gyrus (77.8%/79.7%), left inferior temporal gyrus (83.3%/72.9%), and right superior temporal gyrus (77.8%/71.2%). The left superior temporal pole (92.3%/84.7%), left parahippocampal gyrus (86.5%/81.4%), left Heschl’s gyrus (86.5%/79.7%), and the right superior temporal pole (82.7%/78.0%) revealed most promising diagnostic values for distinguishing AD patients from HCS. Data revealed that lateral temporal and parietal GM volumes distinguish between HCS, MCI, and AD as accurate as hippocampal volumes do; hence, these volumes can be used in the diagnostic procedure. Results also suggest that cognitive functions associated with these brain regions, e.g., language and visuospatial abilities, may be tested more extensively to obtain additional information that might enhance the diagnostic accuracy further.

from the Journal of Alzheimer’s Disease

Tower of London test: A comparison between conventional statistic approach and modelling based on artificial neural network in differentiating fronto-temporal dementia from Alzheimer’s disease

The early differentiation of Alzheimer’s disease (AD) from frontotemporal dementia (FTD) may be difficult. The Tower of London (ToL), thought to assess executive functions such as planning and visuo-spatial working memory, could help in this purpose.

from Behavioural Neurology

Swallowing Intentional Off-State in Aging and Alzheimer’s Disease: Preliminary Study

Frontal cortical activation is elicited when subjects have been instructed not to initiate a sensorimotor task. The goal of this preliminary fMRI study was to examine BOLD response to a “Do Not Swallow” instruction (an intentional “off-state”) in the context of other swallowing tasks in 3 groups of participants (healthy young, healthy old, and early Alzheimer’s disease (AD)). Overall, the older group had larger, bilaterally active clusters in the cortex, including the dorsomedial prefrontal cortex during the intentional swallowing off-state; this region is commonly active in response inhibition studies. Disease-related differences were evident where the AD group had significantly greater BOLD response in the insula/operculum than the old. These findings have significant clinical implications for control of swallowing across the age span and in neurodegenerative disease. Greater activation in the insula/operculum for the AD group supports previous studies where this region is associated with initiating swallowing. The AD group may have required more effort to “turn off” swallowing centers to reach the intentional swallowing off-state.

from the Journal of Alzheimer’s Disease

Screening for Alzheimer’s Disease Among Illiterate Elderly: Accuracy Analysis for Multiple Instruments

One of the challenges in screening for dementia in developing countries is related to performance differences due to educational and cultural factors. This study evaluated the accuracy of single screening tests as well as combined protocols including the Mini-Mental State Examination (MMSE), Verbal Fluency animal category (VF), Clock Drawing test (CDT), and Pfeffer Functional Activities Questionnaire (PFAQ) to discriminate illiterate elderly with and without Alzheimer’s disease (AD) in a clinical sample. Cross-sectional study with 66 illiterate outpatients diagnosed with mild and moderate AD and 40 illiterate normal controls. Diagnosis of AD was based on NINCDS-ADRDA. All patients were submitted to a diagnostic protocol including a clinical interview based on the CAMDEX sections. ROC curves area analyses were carried out to compare sensitivity and specificity for the cognitive tests to differentiate the two groups (each test separately and in two by two combinations). Scores for all cognitive (MMSE, CDT, VF) and functional assessments (PFAQ) were significantly different between the two groups (p < 0.001). The best screening instruments for this sample of illiterate elderly were the MMSE and the PFAQ. The cut-off scores for the MMSE, VF, CDT, and PFAQ were 17.5, 7.5, 2.5, and 11.5, respectively. The most sensitive combination came from the MMSE and PFAQ (94.1%), and the best specificity was observed with the combination of the MMSE and CDT (89%). Illiterate patients can be successfully screened for AD using well-known screening instruments, especially in combined protocols.

from the Journal of Alzheimer’s Disease

Cognitive reserve and Alzheimer’s disease biomarkers are independent determinants of cognition

The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer’s disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-β load via cerebral spinal fluid amyloid-β1–42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. We included 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer’s disease, from the Alzheimer’s Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer’s disease in a group labelled ‘cognitively impaired’ subjects. Structural Abnormality Index scores, which reflect the degree of Alzheimer’s disease-like anatomic features on magnetic resonance images, were computed for each subject. We assessed Alzheimer’s Disease Assessment Scale (cognitive behaviour section) and mini-mental state examination scores as measures of general cognition and Auditory–Verbal Learning Test delayed recall, Boston naming and Trails B scores as measures of specific domains in both groups of subjects. The number of errors on the American National Adult Reading Test was used as a measure of environmental enrichment provided by educational and occupational attainment, a component of cognitive reserve. We found that in cognitively normal subjects, none of the biomarkers correlated with the measures of cognition, whereas American National Adult Reading Test scores were significantly correlated with Boston naming and mini-mental state examination results. In cognitively impaired subjects, the American National Adult Reading Test and all biomarkers of neuronal pathology and amyloid load were independently correlated with all cognitive measures. Exceptions to this general conclusion were absence of correlation between cerebral spinal fluid amyloid-β1–42 and Boston naming and Trails B. In contrast, white matter hyperintensities were only correlated with Boston naming and Trails B results in the cognitively impaired. When all subjects were included in a flexible ordinal regression model that allowed for non-linear effects and interactions, we found that the American National Adult Reading Test had an independent additive association such that better performance was associated with better cognitive performance across the biomarker distribution. Our main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer’s disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-β1–42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer’s disease pathology.

from Brain

Sustained Effects of Once-Daily Memantine Treatment on Cognition and Functional Communication Skills in Patients with Moderate to Severe Alzheimer’s Disease: Results of a 16-Week Open-Label Trial

The present study evaluated the effects of once-daily memantine (20 mg) treatment on cognition and communication in patients with moderate to severe Alzheimer’s disease (AD). In a multicenter, single-arm open-label study, outpatients diagnosed with AD (MMSE < 20; n = 97) were titrated from 5 mg to 20 mg once-daily memantine over 4 weeks. Once-daily memantine treatment (20 mg) was then continued for 8 weeks, followed by a 4-week wash-out period. The primary efficacy endpoint was the change from baseline in the Consortium to Establish a Registry for Alzheimer's Disease -Neuropsychological Battery (CERAD-NP) total score. Secondary efficacy endpoints included change from baseline in Functional Communication Language Inventory (FLCI) and ADCS-ADL19 total score, and the response from baseline in Clinical Global Impression of Change (CGI-C). The CERAD-NP total score improved significantly after 12 weeks of once-daily memantine treatment compared with baseline (5.9 ± 8.8; p < 0.0001). The FLCI total score improved significantly after 12 weeks compared with baseline (4.4 ± 6.8; p < 0.0001). These significant improvements were already observed after 4 and 8 weeks of once-daily memantine treatment and persisted after a 4-week wash-out period. ADCS-ADL19 total scores showed only slight increases from baseline, and CGI-C indicated that the majority of patients experienced an improvement or stabilization of the disease after 12 weeks. At least one Treatment-Emergent Adverse Event was reported by 38 (39.2%) patients. In patients with moderate to severe AD, once-daily memantine (20mg) treatment significantly improved cognition and functional communication and was found to have a favorable safety and tolerability profile.

from the Journal of Alzheimer’s Disease

Performance on a measure of category fluency in cognitively impaired elderly

Measures of verbal fluency are widely used in the assessment of cognitive functioning of the elderly. However, limited research has evaluated patterns (across specific timed intervals) of performance on tasks of language fluency in different forms of dementia. The current study investigated semantic fluency in 488 elderly individuals (249 with Alzheimer’s dementia, 97 Vascular dementia, 97 Mild Cognitive Impairment and 45 cognitively intact) across 15-second intervals in an animal naming task using retrospective chart review. Normal controls produced significantly more exemplars and AD patients produced fewer animal names than the other groups. After the first 15- second time interval, the demented groups produced significantly fewer exemplars than the non-demented. At the end of 30 seconds it was possible to differentiate normal aging from MCI who no longer differed from the VaD group. Overall, it appears that the greatest and most clinically meaningful differences between the diagnostic groups were detected in the first three 15-second intervals. The present findings support the use of time intervals and total scores on tasks of verbal fluency in clinical settings and for research purposes.

from Aging, Neuropsychology, and Cognition

Cognitive phenotypes in Alzheimer’s disease and genetic variants in ACE and IDE

Alzheimer’s disease (AD) is generally considered to be a disorder primarily affecting memory. It is increasingly recognized that the clinical presentation or “cognitive phenotype” is variable. The apolipoprotein E ε4 (APOE ε4) allele has been associated with an amnestic presentation, but does not appear to fully explain the high prevalence of family history within this group. We examined polymorphisms in the genes ACE and IDE in relation to cognitive phenotype. In this study 276 participants with AD were categorized into 1 of 4 cognitive phenotype classifications: typical, amnestic, language, and posterior. Family history and possession of the APOE ε4 allele were most prevalent in the amnestic group. Of the 10 genetic variants of IDE, and the 3 genetic variants of ACE studied, only ACErs4291 and ACErs1800764 were nominally associated with the amnestic presentation.

from Neurobiology of Aging

Morphological Cerebral Correlatesof CERAD Test Performance in Mild Cognitive Impairment and Alzheimer’s Disease

The objective of this study was to investigate the associations between structural cerebral changes and neuropsychological deficits in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Sixty patients with MCI, 34 patients with mild to moderate AD, and 32 healthy controls underwent both extensive neuropsychological assessment (CERAD test battery) and high-resolution structural magnetic resonance imaging. We used optimized voxel based morphometry to investigate (i) differences in gray matter density between the three aforementioned groups and (ii) the putative relations of CERAD test performance with atrophic brain changes. When compared to the healthy controls, the AD patients and, to a lesser extent, patients with MCI showed significant density losses predominantly in the medial temporal lobe. Deficits in verbal fluency and word finding were significantly correlated with left fronto-temporal and left temporal (including the hippocampus) changes, respectively. Decreased scores in immediate and delayed recall and in delayed recognition were associated with several cortical and subcortical sites including the parahippocampal and posterior cinguli gyri, the right thalamus, and the right hippocampus, whereas deficits in constructional praxis and constructional praxis recall referred to sites in the left thalamus and cerebellum, and the temporal cortices (bilaterally), respectively. Our findings lend further support for medial temporal lobe degeneration in MCI and AD and demonstrate that cognitive deficits as assessed on the CERAD do not simply refer to specific changes in discrete cerebral sites but rather reflect morphological alterations in widespread networks.

from the Journal of Alzheimer’s Disease

The Effects of Age, Sex and Alzheimer’s Disease on Strategy Use During Verbal Fluency Tasks

Clustering and switching strategies during phonemic and semantic verbal fluency tasks were investigated in healthy adults (n = 193, 86 males, 20-90 years) in young, middle-aged, young-old, and old-old age groups (Study 1). Older groups produced fewer total words and lower switching scores; males relied more on clustering and females on switching to produce equivalent output. In Study 2, early Alzheimer’s disease participants, compared to healthy older adults, (n = 26 per group) produced fewer total words and smaller average clusters. Sex, age, and clinical differences on switching and clustering strategies support a dual processing model of verbal fluency.

from Aging, Neuropsychology, and Cognition

An analysis of communication in conversation in patients with dementia

Patients with degenerative dementia often show language disorders, but little is known about their verbal (VC) and non-verbal communication (NVC). Our aim was to analyse VC and NVC in patients with standard criteria of mild-moderately severe dementia (MMSE ≥ 14/30) resulting from Alzheimer’s disease (AD; 29 cases), behavioural variant of frontotemporal dementia (FTD; 16), or dementia with Lewy bodies (DLB; 13). We used the Lille Communication Test, which addresses three domains: participation in communication (PC: greeting, attention, participation), VC (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics and verbal feedback), and NVC (understanding gestures, affective expressivity, producing gestures, pragmatics and feedback). Patients were compared with 47 matching control subjects. AD patients were partially impaired (p≤0.01) in PC (greeting), and more definitely in VC, especially by verbal comprehension and word finding difficulties and to a much lesser degree in verbal pragmatics (responding to open questions, presenting new information), while NVC was mostly preserved. FTD patients were severely impaired in PC. VC difficulties were related to lexical-semantic, syntactic and more specifically pragmatic problems. NVC was impaired by difficulties in affective expressivity, pragmatics and feedback management. DLB patients showed modest difficulties with VC. PC, VC and NVC strongly correlated with performance in the dementia rating scale. In conclusion, the profile of communication difficulties was quite different between groups. FTD patients showed most severe difficulties in PC and verbal and non-verbal pragmatics, in relation to their frontal lesions. AD patients had prominent impairment of lexical-semantic operations.

from Neuropsychologia

Emotional Prosody Perception and Production in Dementia of the Alzheimer’s Type

Conclusions: Implications are discussed regarding impaired emotional prosody in DAT, and the utility of objective acoustic measures in revealing subtle deficits and overcoming methodological inconsistencies is emphasized. Further research is critical in advancing our understanding of this pervasive disorder and is important, clinically, in the provision of specific interventions.

from the Journal of Speech, Language, and Hearing Research

Comparison of verbal memory impairment rates in mild cognitive impairment

There are no accepted guidelines establishing the most sensitive neuropsychological methods to define memory impairment in mild cognitive impairment (MCI). We investigated whether similar impairment rates were observed between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Logical Memory (LM) in 90 patients with amnestic or amnestic plus MCI. On HVLT-R delayed recall, 80% of participants performed in the MCI range compared to only 32.2% on LM II. The same pattern was seen for both amnestic and amnestic plus subtypes. Individuals impaired on HVLT-R delayed recall performed significantly worse on LM first recall and on delayed recall of LM Story A than those not impaired. MCI patients with executive dysfunction performed significantly worse than patients with no executive impairment on both LM I and HVLT-R Total Learning, but not for delayed recall of either measure. Future studies can address the longitudinal course of impairment on these measures.

from the Journal of Clinical and Experimental Neuropsychology

Cortical Activation during Clock Reading as a Quadratic Function of Dementia State

In patients with Alzheimer’s disease (AD), neuroimaging studies have demonstrated decreased brain activation, while increased activation was detected in patients with mild cognitive impairment (MCI). It can be hypothesized that increased cerebral activity seen in patients with MCI reflects neural compensation at the beginning of neurodegenerative processes. Later, as patients develop AD, neural integrity is increasingly impaired. This is accompanied by decreased neural activation. In this study we examined cognitive performance and functional magnetic resonance imaging activation on a Clock Reading task (CRT) and a Spatial Control task (SCT) in healthy controls, patients with MCI, and patients with early AD. Correlations between neural-functional activation and cognitive state, measured by the Mini Mental Status Examination, were determined using rank, linear and quadratic correlation models. It could be shown that CRT, in comparison to SCT, specifically activates brain regions in the ventral visual stream and precuneus known to be involved in conceptual processing and spatial imagery. The correlation between brain activity and cognitive state followed a quadratic rather than a linear pattern in several brain regions, including the lingual gyrus, cuneus, and precuneus. The strongest brain activity was found in patients with MCI and less severely impaired early AD subjects. These findings support the hypothesis that patients in early stages of dementia compensate for neuronal loss by the recruitment of additional neural resources reflected by increased neural activation, as measured by the blood oxygen level-dependent signal.

from the Journal of Alzheimer’s Disease

The Amnestic Syndrome of Hippocampal in Alzheimer’s Disease: an MRI Study

The Free and Cued Selective Reminding Test (FCSRT) is a verbal episodic memory test used to identify patients with mild Alzheimer’s disease (AD). The present study investigates the relationships between performance on FCSRT and grey matter atrophy assessed with structural MRI in patients with AD. Three complementary MRI-based analyses (VBM analysis, ROI-based analysis, and three-dimensional hippocampal surface-based shape analysis) were performed in 35 patients with AD to analyze correlations between regional atrophy and their scores for episodic memory using the FCSRT. With VBM analysis, the total score on the FCSRT was correlated with left medial temporal lobe atrophy including the left hippocampus but also the thalami. In addition, using ROI-based analysis, the total recall score on the FCSRT was correlated with the left hippocampal volume. With three-dimensional hippocampal surface-based shape analysis, both free recall and total recall scores were correlated with regions corresponding approximately to the CA1 field. No correlation was found with short term memory scores using any of these methods of analysis. In AD, the FCSRT may be considered as a useful clinical marker of memory disorders due to medial temporal damage, specially the CA1 field of the hippocampus.

from the Journal of Alzheimer’s Disease