Sven-Erik Fernaeus

White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype

To analyse the influence of apolipoprotein E (APOE) genotype on the extent of white matter lesions (WMLs) in Alzheimer’s disease (AD), we examined 60 AD patients with magnetic resonance imaging. The WMLs were rated visually in different brain regions. The patients with the APOE genotype σ4/4 had more extensive WMLs in the deep white matter than patients with genotypes σ3/3 and σ3/4. There was a correlation with age for WMLs in the deep white matter in patients with the APOE σ3/3 genotype. In patients carrying at least one σ4 allele, the WMLs showed no age correlation. The results could imply that in APOE allele σ4 carriers, the WMLs represent a pathological process related to the aetiology of the disease.

Impaired verb fluency: A sign of mild cognitive impairment

We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimers disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive Impairment differed significantly from Subjective Cognitive Impairment and Alzheimers disease. Reduced verb fluency thus appears to be a linguistic marker for incipient dementia. One possibility is that the verb fluency deficit in Mild Cognitive Impairment results from degenerative processes known to occur in the parahippocampal region.

A temporal lobe factor in verb fluency.

Verb fluency requires self-sustained verb retrieval. The brain correlates of this task are virtually unknown. We investigated the relations between verb and noun (semantic) fluency and regional brain perfusion in subjects with varying degrees of cognitive decline, ranging from very mild subjective impairment to Alzheimers disease (AD). Data consisted of single-photon emission computed tomography (SPECT) data and temporally resolved verb and noun fluency scores from 93 participants. Impaired verb fluency was predicted by a temporal lobe hypoperfusion factor and low education, whereas high age and low perfusion in the parietotemporal-occipital region predicted impaired noun fluency. Analysis of perfusion within the temporal region indicated primary involvement of the temporal pole and medial temporal lobe in AD. This might reflect pathology of the anterior parahippocampal region, which appears early in neurodegenerative disease. Although temporal lobe structures have not usually been implicated in verb processing, early temporal pathology thus appears to contribute to impaired verb fluency in cognitive decline.

Cut the coda : Early fluency intervals predict diagnoses

The aim of this study was threefold: (i) to clarify whether letter and category fluency tap different cognitive abilities; (ii) to make diagnostic comparisons and predictions using temporally resolved fluency data; (iii) to challenge and test the widely made assumption that 1-min sum scores are the fluency test measure of choice in the diagnosis of dementia. Scores from six 10-sec intervals of letter and category fluency tests were obtained from 240 participants including cognitive levels ranging from mild subjective cognitive complaints to Alzheimers disease. Factor analysis revealed clearly separate factors corresponding to letter and category fluency. Category fluency was markedly impaired in Alzheimers disease but not in Mild Cognitive Impairment. Only scores from relatively early intervals predicted Alzheimers disease and Mild Cognitive Impairment. The conclusions are (i) letter and category fluency are different tests, category fluency being the best diagnostic predictor; (ii) it would be possible to administer category fluency tests only for 30 sec, because after this point the necessary differential diagnostic information about the patients word fluency capacity has already been gathered.

White matter lesions impair initiation of FAS flow.

Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137–143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer’s disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.

Word sequence production in cognitive decline: Forward ever, backward never

Backward recall of automatic word sequences involves declarative and working memory abilities known to be impaired in the early stages of cognitive decline. Yet its utility in the diagnosis of mild cognitive impairment and mild dementia has not been studied in detail. We analysed word sequence production in 234 participants drawn from three categories: subjective cognitive impairment, mild cognitive impairment, and mild dementia in Alzheimers disease. The names of the months were used as a diagnostic target for investigating forward versus backward sequence production. Forward production remained normal across categories. In contrast, backward speed was significantly decreased in mild cognitive impairment. In dementia both speed and accuracy were impaired. Backward production had significant diagnostic classificatory power. We conclude that word sequence production yields data relevant to the diagnosis of dementia with a minimum of time and expense.

Jargonagraphia in a Case of Frontotemporal Dementia

Jargonagraphia is known to occur after discrete brain lesions but not in primary degenerative dementia. We report a patient with frontotemporal dementia who developed jargonagraphia and nonfluent aphasia. Written output was graphically preserved but consisted of short words intermingled with abstruse neologisms. MRI showed predominant right frontotemporal cortical atrophy accompanied by white matter hyperintensities in the right anterior subcallosal periventricular region. Diagnosis and MRI were corroborated by extensive neuropathological findings obtained 8 months later. The agraphia in this case is discussed with reference to both specific macroscopic and microscopic pathoanatomical lesions. We suggest that jargonagraphia can appear in frontotemporal dementia depending on the localization of lesions.

Late reaction times identify MCI

A group of 172 mild cognitive impairment (MCI) patients and 79 healthy control participants (HC) were tested on simple reaction time (SRT). There was a significant difference between MCI and HC in mean SRT. The test could be partitioned into five segments of 16 trials each, but RTs were not always available for each partition. However, scores from each segment for 166 MCI and 41 of the HCs were available. These data showed that a significant interaction between RT-partition and diagnostic category was the main source of the difference between groups. The interaction indicated that MCI patients performed at about the same level as HC in the initial three of the five segments of the test, but were significantly impaired during the last two segments of the 80 trials. The results were interpreted as impaired sustained attention among a large part of the MCI group, and the study shows the importance of taking into account all available data resulting from this type of test.

Memory factors in Rey AVLT: Implications for early staging of cognitive decline

Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory-Verbal Learning Test (RAVLT). The major groups were patients with Alzheimers disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment.

Conceptual elaboration versus direct lexical access in WAIS-similarities: differential effects of white-matter lesions and gray matter volumes

ABSTRACT Wechsler Adult Intelligence Scale (WAIS) subscale Similarities have been classified as a test of either verbal comprehension or of inductive reasoning. The reason may be that items divide into two categories. We tested the hypothesis of heterogeneity of items in WAIS-Similarities. Consecutive patients at a memory clinic and healthy controls participated in the study. White-matter hyperintensities (WMHs) and normalized temporal lobe volumes were measured based on Magnetic resonance Imaging (MRI), and tests of verbal memory and attention were used in addition to WAIS-Similarities to collect behavioural data. Factor analysis supported the hypothesis that two factors are involved in the performance of WAIS-similarities: (1) semiautomatic lexical access and (2) conceptual elaboration. These factors were highly correlated but provided discriminative diagnostic information: In logistic regression analyses, scores of the lexical access factor and of the conceptual elaboration factor discriminated patients with mild cognitive impairment from Alzheimer’s disease patients and from healthy controls, respectively. High scores of WMH, indicating periventricular white-matter lesions, predicted factor scores of direct lexical access but not those of conceptual elaboration, which were predicted only by medial and lateral temporal lobe volumes.