Biomedical subjects

O Almkvist

Publications and source records attributed to O Almkvist.

At least 19 recordsLinked to original sources

PubMed2000

Functional changes in brain activity during priming in Alzheimer's disease.

Patients with Alzheimer's disease (AD) are often impaired on certain forms of implicit memory, such as word-stem completion priming (WSCP). Lesion data suggest that deficient WSCP may be associated with abnormal functioning in the posterior neocortex. Using positron emission tomography (PET), we here provide direct support for this view. Compared with normal old adults, AD patients showed reduced priming on a word-stem completion task. The normal old showed decreased activity in right occipital cortex (area 19), whereas the AD patients showed increased activity in this region during priming. To the extent that decreased activity during priming reflects an experience-dependent reduction of the neuronal population involved, these results indicate that shaping of the relevant neurons is slower in AD, possibly as a result of inadequate initial stimulus-processing.

Adult↗

PubMed1999

Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease.

OBJECTIVE: To examine patterns of brain activation during verbal episodic retrieval in normal elderly subjects and patients in an early phase of AD. BACKGROUND: It is established that 1) a profound episodic memory impairment is a cardinal symptom of AD; and 2) some of the earliest brain changes in this disease occur in regions critical to episodic memory, such as the hippocampus and neighboring regions. Yet, it remains largely unknown whether the episodic memory deficit seen in AD is paralleled by concomitant alterations in brain activity during actual task performance in these or other brain areas. METHODS: Using PET, blood flow was assessed in normal elderly subjects and patients with early AD during two retrieval conditions involving completion of word stems: baseline and cued recall. RESULTS: The patients with AD showed a marked performance deficit in cued recall, although the two groups were indistinguishable in the baseline task condition. Both groups showed bilateral activity in orbital and dorsolateral prefrontal cortex, left precuneus, and right cerebellum, as well as decreased activity in distinct left temporal regions during cued recall. The normal elderly alone activated the left parietal cortex and the left hippocampal formation during episodic retrieval. By contrast, AD-related increases in activity during cued recall were observed in the left orbital prefrontal cortex and left cerebellum. CONCLUSIONS: The similar patterns of activations in the two groups suggest that a large distributed network involved in episodic memory retrieval functions relatively normally in early AD. Those retrieval activations seen in the normal elderly, as opposed to the patients, may reflect AD-related failures in semantic processing and successful recollection of the target information, respectively. Finally, the AD-related increases in activity were interpreted in terms of compensatory reactions to the difficulties in performing the episodic memory task.

Aged↗

PubMed1999

Early diagnosis of Alzheimer dementia based on clinical and biological factors.

Alzheimer's disease (AD) is common in elderly individuals; it causes distress for the patients and their relatives as well as large costs for the society. With the advent of symptomatic treatment at present and probable etiology-based cures in the future, it will be possible to relieve and put an end to these negative effects. Therefore, it is necessary to diagnose the disease as early as possible. In this review, we briefly summarize the state-of-the-art concerning various available clinical and biochemical methods for identifying AD. Increasing age, heritage, and presence of ApoE e4 allele have been confirmed as risk factors for AD as well as some putative factors (e.g., low education, hypertension, hypotension) based on epidemiological recent research. Selective impairment of episodic memory has been found to be a preclinical marker for future development of AD based on convergent data from asymptomatic AD-related mutation carriers, longitudinal studies of patients with mild cognitive impairment (MCI), and epidemiological studies of incident AD cases. Neurophysiological methods are inexpensive and useful for the identification of changes in brain dysfunction in AD and new promising methods are under development. Using magnetic resonance imaging (MRT), structural measurements of brain atrophy and specific brain structures such as the hippocampus have been reported to detect dementia development early in the course of disease. Similarly, functional measurements of brain activity (e.g., blood flow) have revealed that hypometabolism in bilateral parietotemporal brain areas early in the disease course. Finally, biochemical studies have demonstrated that certain proteins (e.g., tau the A beta 1-42/43 metabolite of the amyloid precursor protein) may be associated with the disease process in AD, although the specificity of these markers remains to be established. It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD.

Age Factors↗

PubMed1999

Cognitive support at episodic encoding and retrieval: similar patterns of utilization in community-based samples of Alzheimer's disease and vascular dementia patients.

The hypothesis that Alzheimer's disease (AD) and vascular dementia (VaD) differ in the pattern of episodic memory was examined in this study. Demented patients with AD and VaD and normal old adults were assessed on episodic memory tasks, including free recall and recognition of slowly and rapidly presented unrelated words and free and cued recall of organizable words. Results showed a general deficit in both demented groups across all memory variables, although the AD and VaD patients were indistinguishable across all measures. The normal old showed proficient utilization of more study time, organizability, and category cues. By contrast, the AD and VaD patients were able to benefit from cognitive support only when guidance was provided at both encoding and retrieval. In addition, in the normal old, recall of unrelated words was characterized by a relatively equal contribution from primary and secondary memory, whereas the demented patients relied predominantly on primary memory. The results suggests a similarity between AD and VaD patients with regard to the nature of the episodic memory impairment, despite etiologic differences between the diseases.

Aged↗

PubMed1998

Longitudinal changes in quantitative EEG during long-term tacrine treatment of patients with Alzheimer's disease.

Quantitative EEG is a potentially useful tool in demonstrating the effects of treatments with acetylcholinesterase (AChE) inhibitors on the progression of Alzheimer's disease (AD). In order to define the profile of EEG changes during tacrine long-term treatment, for 12 months we followed 15 AD patients receiving an optimal individually tolerable dose. After 3 months theta global field power (GFP) was significantly reduced, and after 6 months both theta and delta GFP decreased. Theta GFP was still reduced after 12 months of treatment when compared to the baseline. Significant decreases in fast activities of beta 1 and beta 2 GFP were also observed. The untreated reference group (n = 10) did not show any significant changes in GFP after 12 months follow-up, although generators of theta activity had a significant shift towards posterior regions. These findings suggest that slowing in fast EEG frequencies during chronic treatment with AChE inhibitors may provide an early indicator of declining treatment efficiency.

Aged↗

PubMed1998

Mild cognitive impairment--an early stage of Alzheimer's disease?

The hypothesis that mild cognitive impairment (MCI) represents an early stage of Alzheimer's disease (AD) was investigated by reviewing recent research from three sources: asymptomatic and symptomatic individuals carrying mutations that cause AD, hospital-samples of non-demented patients with MCI at the initial examination that are followed longitudinally, and community-based incident cases of AD. Studies with asymptomatic mutation carriers of the amyloid precursor protein and presenilin 1 gene have shown a linear and disease-related decline in most cognitive functions that begins approximately 10 years before the expected clinical onset of AD. However, there is considerable overlap between the level of impairment for mutation carriers and non-carriers of the same age during the early preclinical stage of AD. Hospital-based longitudinal studies have shown that non-demented individuals with isolated mild episodic memory impairment may develop clinically diagnosed AD with widespread cognitive deficits in a few years time. Community-based epidemiological studies on the incidence of AD demonstrate that indices of episodic memory, in addition to measures of general cognitive functioning, are useful in predicting early AD. In contrast, subjective memory impairment or age-associated memory impairment are less powerful predictors of future dementia development. In summary, there is converging evidence to demonstrate that preclinical AD is characterized by a common behavioral phenotype, with cognitive decline in several domains, predominantly in episodic memory. The decline appears to start many years before the clinical onset of AD. Moreover, the progression of the impairment appears to be continuous. Finally, this pattern of performance generalizes across etiology of AD (familial or sporadic), clinical onset (early or late), sample composition (hospital or community), and method of assessment.

Aged↗

PubMed1998

Impairments of some cognitive functions are common in crash-involved older drivers.

The relationship between limitations in different cognitive functions, measured with a neuropsychological test battery, and moving traffic violations among older drivers was investigated. Thirty-seven drivers aged 65 years or more, with temporarily suspended driving licenses (suspended drivers) were identified 23 were crash-involved and 14 were not. When compared to 31 controls with clean driving records, crash-involved suspended drivers performed less well on tests of visuoconstructive ability (p = 0.008), psychomotor speed (p = 0.019) and visuospatial memory (p = 0.036). Non-crash-involved suspended drivers did not differ from controls. A combination of three tests (of visuoconstructive ability, visuospatial memory and verbal episodic memory) succeeded in correctly classifying 65.2% of the crash-involved suspended drivers. The results support the idea of cognitive decrements as an important causal factor in crashes of older drivers.

Accidents, Traffic↗

PubMed1998

Word production: dissociation of two retrieval modes of semantic memory across time.

To identify components that contribute to word-fluency performance, 126 patients referred to a Memory Clinic for suspected cognitive impairment underwent a neuropsychological examination including the Controlled Oral Word Association test (FAS; Benton & Hamsher, 1976). The number of words produced in the FAS test during six consecutive 10-s periods followed a negatively accelerated curve approaching an asymptotic level after about 30 s. The 18 FAS variables (3 letters x 6 periods) were entered into an exploratory factor analysis resulting in two factors. One factor, linked to a semiautomatic and rapid retrieval from semantic memory, loaded on the initial phase of the FAS test. A second factor, linked to an effortful and slow retrieval from semantic memory, loaded on the later phase of the FAS test. Thus, two retrieval modes of semantic memory contribute differently to the initial and later part of the FAS test, which may have theoretical and practical implications.

Adult↗

PubMed1998

Brain volumes and regional cerebral blood flow in carriers of the Swedish Alzheimer amyloid protein mutation.

As a preliminary part of a longitudinal clinical study of carriers of the Swedish amyloid precursor protein (APP) 670/671 mutation, 13 members of a family were investigated with magnetic resonance imaging (MRI) brain volumetry and single photon emission computed tomography (SPECT) cerebral blood flow (CBF) measurements. Five of the family members were mutation carriers; eight were not carriers. Two carriers were younger than 40 years of age and had no evidence of cognitive dysfunction or structural or functional brain changes. One carrier with 4 years to expected disease onset showed poor performance in episodic memory tests and also slightly low temporal lobe CBF, although there were no clearly abnormal findings. One carrier with mild Alzheimer disease (AD) had no clear structural brain changes, although CBF measurements showed clear reduction of temporal lobe CBF. One carrier with severe AD had both temporal lobe atrophy and CBF reduction. This indicates that in carriers of the APP 670/671 mutation, reduction of regional CBF is more severe than regional atrophy. The clearest change related to development of clinical AD was a reduction of CBF in the basal and lateral temporal lobes. Further longitudinal studies of these subjects are needed to confirm these preliminary findings, which might provide important data regarding early brain changes in AD.

Adult↗

PubMed1998

[Cognitive and affective dysfunction in MS].

Prevalence studies have shown cognitive and affective disorders to be common in multiple sclerosis (MS). Although much is known about the manifestations of such disorders, our knowledge of the cerebral systems involved remains poor. Functional techniques will enable cerebral blood flow to be measured, and sophisticated SPECT (single photon emission computed tomography) techniques can provide a clearer picture of the dynamics of cognitive and affective processes in MS. Increased knowledge of these disorders would enable the management and rehabilitation of MS patients to be improved.

Affective Symptoms↗

PubMed1997

Detection of mild dementia in community surveys. Is it possible to increase the accuracy of our diagnostic instruments?

OBJECTIVE: To investigate the accuracy of cognitive tests and clinical dementia diagnosis in distinguishing between mildly demented and nondemented subjects. DESIGN: Three-year longitudinal follow-up of a community-based cohort sample. Using the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised as criterion variable, subjects were classified as demented and nondemented based on the results of cognitive test performance at time 1. These subjects were then examined prospectively for development of dementia at time 2. PARTICIPANTS: The sample consisted of 63 mildly demented (Mini-Mental State Examination score > 18 < 24) and 398 nondemented subjects at time 1. At follow-up, due to death and refusal of participation, the sample consisted of 108 demented and 217 nondemented subjects. RESULTS: The group of subjects who were considered to be demented according to the results of the cognitive tests and nondemented by the clinical diagnosis at time 1 had a higher incidence of dementia at time 2 than did the subjects who were considered to be nondemented according to both cognitive tests and clinical diagnosis. Among the incident dementia cases, subjects considered to be demented according to the cognitive tests but nondemented by the clinical diagnosis performed at a lower level on most cognitive tests were older, had less education, and consisted of more women than did the group of subjects who were considered to be demented by the clinical diagnosis and nondemented by the cognitive tests at time 1. CONCLUSIONS: A combination of cognitive tests, especially tasks assessing episodic memory, can detect many subjects in a preclinical state of dementia who could be missed in the clinical diagnostic procedure due to subjects' relatively high age, low education, and female sex. However, cognitive tests also may miss a sizable proportion of prevalent dementia cases due to possible insensitivity to the same demographic variables. These findings indicate the need of integration between clinical and cognitive data to increase the accuracy in detecting dementia in an early phase.

Aged↗

PubMed1997

Clinical characteristics of a chromosome 17-linked rapidly progressive familial frontotemporal dementia.

OBJECTIVE: To describe symptoms, signs, neuroimaging results, and neuropathologic findings in patients from a family with chromosome 17q21-linked autosomal dominant frontotemporal dementia. DESIGN: Multiple case report with genetic investigations. SUBJECTS: The disease was observed in a Swedish family and documented in 3 generations. Four siblings are described in this article. RESULTS: A rapidly progressive dementia with genetic linkage to chromosome 17q21 was observed. The mean age of onset was 51 years and the average duration of disease to death was 3 years. Two patients started with speech disturbances leading to a progressive, nonfluent aphasia, 1 patient had onset symptoms of leg apraxia and akinesia and muscular rigidity, and in 1 patient reckless driving was the first symptom. Loss of spontaneous speech developed later in all patients and emotional bluntness in 3 of the patients. Cerebral perfusion was decreased in the frontal areas in all patients. In the person with apraxia as the onset symptom, the cerebral blood flow was also diminished in the left hemisphere, where a slight atrophy was detected on magnetic resonance imaging scans. At the postmortem examination, slight gliosis of the parietal lobes was observed in this patient. In all patients there was a frontocentral degeneration of the cortex with discrete microvacuolation and gliosis. CONCLUSION: Clinical features of frontotemporal dementia, parkinsonism, an early age of onset, a rapid disease progression, and variable onset symptoms were seen in these patients. Two other clinically distinct diseases, dementia with pallido-ponto-nigral degeneration and a disinhibition-dementia-parkinsonism-amyotrophy complex, have recently been mapped to chromosome 17q21. In the family described in this article, genetic linkage was detected to the same region, suggesting the possibility that these diseases may originate from pathogenic mutations in the same gene.

Chromosomes, Human, Pair 17↗

PubMed1997

Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation.

OBJECTIVE: To explore the relationship between possible biological markers of Alzheimer disease that are related to amyloid metabolism and mental functions. PARTICIPANTS: Twelve individuals from a Swedish family with Alzheimer disease and a double mutation at codons 670/671 of the amyloid precursor protein gene participated in the study. DESIGN: Cerebrospinal fluid levels of alpha-secretase cleaved soluble amyloid precursor protein (alpha-sAPP), total sAPP, and amyloid beta-peptide were correlated with data on multiple cognitive functions that covered the whole range of human performance. SETTING: The Alzheimer's Disease Research Centre, Department of Clinical Neuroscience, Section of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden. RESULTS: There were highly significant linear correlations between low levels of alpha-sAPP and poor performance on neuropsychological tests that assessed intelligence, verbal and visuospatial functions, memory, and attention. Within the group of nonmutation carriers, significant correlations were also obtained between the levels of alpha-sAPP and cognitive functions. A less striking association was seen between the levels of total sAPP and cognition. No association was found between the levels of amyloid beta-peptide and cognition. CONCLUSIONS: The strong relationship between alpha-sAPP levels and cognition in both patients with Alzheimer disease and normal-aging persons may imply that alpha-sAPP is involved in basic protective brain processes. Alternatively, less amyloid beta-peptide amounts are produced, leading to diminished plaque formation, when alpha-sAPP is generated.

Adult↗

PubMed1997

Olfactory dysfunction for pyridine and dementia progression in Alzheimer disease.

OBJECTIVE: To investigate whether odor detection sensitivity for pyridine, suggested by previous research not to be affected, is impaired in Alzheimer disease (AD) and whether an association exists between odor threshold and both degree of dementia and rate of dementia progression in AD. METHOD: The method of constant stimuli was used to determine odor thresholds for pyridine in 18 patients with AD (Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) and 16 healthy elderly control subjects. All participants were carefully examined with medical and neuropsychological tests. RESULTS: Six patients with AD but none of the controls were anosmic (total olfactory loss) to pyridine, and the 12 nonanosmic patients had significantly higher detection thresholds (50% probability for detection, 323 parts per billion [ppb]) than did the controls (50% probability for detection, 105 ppb). In addition, an association was found between odor threshold and both degree of dementia and rate of dementia progression in AD. CONCLUSIONS: In contrast to previous findings, our results provide evidence that odor sensitivity in AD is impaired for pyridine. Odor sensitivity, in addition to other suggested predictors of progression rate, may be of interest for defining subgroups of AD or for clinical prognostic judgments of single patients.

Aged↗

PubMed1997

Bilateral temporal lobe volume reduction parallels cognitive impairment in progressive aphasia.

BACKGROUND: Patients with isolated aphasia in the absence of other cognitive abnormalities have been the focus of several studies during the past decade. It has been called primary progressive aphasia (PPA), and the typical features of this syndrome are marked atrophy of the left temporal lobe according to the radiological examination and a language disorder as the initial symptom. In previous studies of PPA, the selection of the patients was based mainly on linguistic symptoms. Now, when computed tomography or magnetic resonance imaging scans are part of the routine investigation of cognitive impairment and suspected dementia, the patients with lobar atrophy will be found at an earlier stage. In the present study, we used a new approach and defined the study group by selecting patients with obvious left temporal lobe atrophy, assessed by MRI, and we referred to them as patients with temporal lobe atrophy (TLA). OBJECTIVE: To identify the features that distinguish TLA from other primary neurodegenerative disorders. PATIENTS: Six patients with TLA were compared with patients with Alzheimer disease (AD), patients with frontal lobe dementia (FLD), and healthy control subjects. METHODS: The investigations included magnetic resonance imaging volumetry, single photon emission computed tomography, and neuropsychologic and linguistic evaluations. RESULTS: In the TLA group, the mean volume of the left temporal lobe was 35% smaller than the right, while in the AD and FLD groups, the atrophy was symmetrical and bilateral. In the TLA group, the absolute volumes of the temporal lobes were significantly smaller on the left side compared with the AD and FLD groups, whereas there was no difference on the right side. The cerebral blood flow pattern in TLA was asymmetric and differed from that in the other study groups. All patients with TLA had a history of progressive Wernicke-type aphasia, ranging from 2 to 6 years. They showed primary verbal memory impairment but had preserved visuospatial functions. The clinical condition of all patients with TLA deteriorated during the study period; severe aphasia developed, and the patients exhibited signs of frontal lobe dysfunction. Serial volumetric measurements in 4 of 6 patients showed an annual 8% to 9% decrease of both left and right temporal lobes. CONCLUSIONS: The initial marked asymmetry in cognitive function found in patients with TLA contrasts with the general decline found in patients with AD. The bilateral degenerative process evident in patients with TLA paralleled the clinical deterioration, indicating TLA to be a non-AD lobar atrophy that develops into generalized cognitive dysfunction and dementia.

Aged↗

PubMed1997

EEG-microstates in mild memory impairment and Alzheimer's disease: possible association with disturbed information processing.

The only available functional neuroimaging methods reaching the time resolution of human information processing are EEG and MEG. Since spectral analysis implies analysis of longer time epochs, the high temporal resolution of EEG is partly lost. By dividing the EEG in the time-domain into segments of similar spatial distribution on the scalp (microstates) it has been possible to assess patterns of neuronal activity representing the information process currently performed by the brain. In the present study alterations of EEG microstates in subjective (n = 31) and objective (n = 38) memory impairment as well as in probable Alzheimer disease (DAT: n = 64) compared to healthy controls (n = 21) were investigated. The main findings were reduced segment durations and a more anterior center of gravity of the microstate topography in DAT. With more pronounced cognitive dysfunction larger window sizes were found. Shorter microstates and larger windows reflect more rapidly changing spatial activation patterns, and are interpreted as an impaired capability to establish stable brain states necessary for normal brain function. The anteriorization of the microstates is consistent with results in the frequency domain and may reflect neuropathological changes in DAT.

Aged↗

PubMed1997

Cognitive predictors of incident Alzheimer's disease: a prospective longitudinal study.

The present study examined whether cognitive variables measured at baseline could predict incident cases of Alzheimer's disease (AD) after a 3-year follow-up period. Twenty-six incident AD adults and 179 very old (M = 83.5 years) adults without dementia participated in a population-based study. Cognitive performance was indexed by the Mini-Mental State Examination (MMSE) and multiple indices of memory and visuospatial and verbal performance. A logistic regression analysis that controlled for age, gender, and education indicated that MMSE scores were reliable indicators of who would develop AD. In addition, recall of organizable words, recognition of faces, and letter fluency were reliable predictors of subsequent dementia status after differences in MMSE performance were partialed out. Thus, although the MMSE is useful in predicting dementia, there is an additional advantage of assessing specific indices of cognitive functioning. Further, supportive episodic memory tasks may be more salient predictors of incident AD than tasks that offer less supportive encoding or retrieval conditions.

Aged↗

PubMed1997

Extradural morphine gives better pain relief than patient-controlled i.v. morphine after hysterectomy.

We examined if patient-controlled analgesia (PCA) with i.v. morphine provided comparable postoperative analgesia after hysterectomy as extradural morphine, without increasing the incidence of side effects. The study (n = 40) was randomized and double-blind. An extradural catheter was inserted before surgery and anaesthesia was standardized. The extradural group received extradural morphine 0.06 mg kg-1 by the end of surgery and a second dose 6 h later. The i.v. group received an i.v. infusion of morphine 0.2 mg kg-1 after surgery. PCA with morphine 0.04 mg kg-1 i.v. was used in both groups. Pain relief (VAS), side effects and cognitive functions were evaluated for 18 h. Plasma samples were obtained for analysis of morphine concentrations. Mean consumption of PCA morphine was 2.4 mg h-1 for the i.v. group and 1 mg h-1 for the extradural group. Despite unlimited access to morphine, the i.v. group had higher VAS scores as the extradural group (P < 0.001). Plasma concentrations of morphine varied 8-10-fold in both groups. In the i.v. group itching, tiredness, blurred vision and vertigo correlated with cumulative consumption of i.v. morphine whereas in the extradural group this correlation existed only for tiredness. Both groups showed reduced ability to perform tests of cognitive function, indicating a central effect of both i.v. and extradural morphine, despite markedly lower plasma morphine concentrations in the extradural group.

Adult↗