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E Hogervorst

Publications and source records attributed to E Hogervorst.

At least 19 recordsLinked to original sources
PubMed2006

Cases with mild cognitive impairment and Alzheimer's disease fail to benefit from repeated exposure to episodic memory tests as compared with controls.

Memory tests may be predictive for cognitive decline. We investigated the sensitivity and change in performance over time of the Hopkins Verbal Learning Test (HVLT) and the Mini-Mental Status Examination (MMSE) for Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) when compared to cognitively healthy controls. Participants included elderly controls (n = 54), MCI (n = 19) and AD cases (n = 28) from OPTIMA. The MMSE and the HVLT (version 1) were administered twice to all subjects with an interval of 2-3 years.MCI and AD cases had poorer performance than controls on the HVLT and MMSE at both testing episodes (p < 0.05). The HVLT profile over time showed a learning effect in the control group (P < 0.0001), a trend to decline in the AD group (p = 0.09) and no change in the MCI group (P = 0.8). A subgroup of MCI subjects had lower HVLT scores at follow-up. The MMSE profile showed no significant change over time for all three groups (P > 0.05). The HVLT had better sensitivity and specificity compared to the MMSE for detecting MCI and AD. The HVLT is not only valuable for cross-sectional designs but has also proved to be valuable in a longitudinal design. Cognitively healthy controls showed evidence of learning strategies on the HVLT after a 2-3 year interval, with improved scores at the second testing episode. By contrast, an MCI group showed no benefits of previous exposure to this test. Lack of use of learning strategies on the HVLT may be an important marker of the likelihood of cognitive decline to MCI or dementia.

Aged↗
PubMed2005

Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review.

Low testosterone (T) levels may predispose to Alzheimer disease (AD), but it is unclear whether this is a co-morbid effect due to cachexia, subclinical hyperthyroidism or other co-morbidity. The biological plausibility for potential protective effects of T on brain functions is substantial. In addition, higher levels of gonadotropins found in older cases with AD suggest that low levels of T are not due to brain degeneration and that the hypothalamic-pituitary-gonadal (HPG) axis is still intact. Men genetically at risk for AD were also already found to have lower levels of T. However, despite having lower levels of T, women do not show accelerated cognitive decline with age when compared to men. In addition, castration has not necessarily shown a decline in cognitive functions; some studies even found improvement of memory recall. Age may be an important factor when assessing optimal levels of T and several studies suggest that free or bioavailable T may be a better marker than total T levels when investigating associations of androgen activity with cognitive function. Small-scale T intervention trials in elderly men with and without dementia suggest that some cognitive deficits may be reversed, at least in part, by short term T supplementation. Age and prior hypogonadism may play an important role in therapy success and these factors should be investigated in more detail in future large scale randomized controlled studies. For elderly women, T treatment does not seem to have additional benefits over estrogen treatment for postmenopausal complaints and cognitive decline and may increase cardiovascular disease.

Aged↗
PubMed2004

Thyroid function, depressed mood, and cognitive performance in older individuals: the Maastricht Aging Study.

The hypothesis was tested that thyroid function, as indicated by serum thyroid-stimulating hormone (TSH) level, is associated with cognitive performance in a healthy aging population. In a random sample of 120 participants recruited from the Maastricht Aging Study (MAAS), aged between 49 and 71 years, we assessed TSH level, mood state (Symptom Check List, subscale depression), and three domains of cognitive function: verbal memory, general sensorimotor speed, and complex flexibility. After correction for age, sex, and educational level, a negative association between TSH and memory function was apparent: higher levels of TSH predicted lower levels of memory performance. Exclusion of individuals with TSH levels suspect for thyroid disorder (n=2) or who were on thyroid replacement (n=3) attenuated this association. Furthermore, additional control for mood status reduced the association below the significance level. No interaction between age and TSH on cognition was found, which indicated that the TSH-memory association was independent of age group level. We conclude that the association between TSH level and memory performance was small and dependent on mood status and the presence of (possible) thyroid disease in this relatively healthy population based sample. Prospective studies are needed to address the role of thyroid function in age-related cognitive decline.

Affect↗
PubMed2003

Association of the androgen receptor CAG repeat polymorphism with Alzheimer's disease in men.

We examined the CAG repeat polymorphism in exon 1 of the androgen receptor (AR) in an Oxford cohort of 150 cases (101 men) of definite or probable Alzheimer's disease (AD) and 190 elderly controls (140 men). We found that short alleles (< or = 20 CAG repeats) were associated with AD (adjusted odds ratio = 2.5, 95% confidence intervals: 1.2-5.0) in men, but not in women. This association appeared stronger in early-onset AD (< 65 years). We conclude that this AR polymorphism is of potential relevance to the risk of AD in men.

Aged↗
PubMed2003

Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: Early diagnosis of dementia is important for those who might benefit from treatment. We designed a brief comprehensive neuropsychological test battery to help differentiate control subjects from patients with mild cognitive impairment (MCI) and dementia. METHOD: The battery included tests of memory, attention, executive function, speed, perception and visuospatial skills. It was administered to subjects from the OPTIMA cohort: 51 controls, 29 with MCI, 60 with 'possible' or 'probable' Alzheimer's disease (AD) (NINCDS/ADRDA) and 12 with cerebrovascular disease (CVD). Mann-Whitney U tests were used to compare performance of controls with other diagnostic groups. The sensitivity and specificity of the tests were determined using Receiver Operating Characteristic curve analyses. The effects of age, gender and years of education on test performance were determined with Spearman's rank correlations. RESULTS: The AD group performed worse than controls on all tests except an attention task. The Hopkins Verbal Learning Test and The Placing Test for episodic memory showed significant discriminative capacity between controls and other groups. Attention and processing speed tests discriminated CVD from controls. Category fluency, episodic memory tests and the CLOX test for executive function distinguished MCI from AD. Spearman's correlations showed negative associations between age and processing speed. Years of education affected performance on all tests, except The Placing Test. CONCLUSIONS: Certain neuropsychological tests have been shown to be sensitive and specific in the differential diagnosis of various types of dementia and may prove to be useful for detection of MCI.

Aged↗
PubMed2003

The validity and reliability of 6 sets of clinical criteria to classify Alzheimer's disease and vascular dementia in cases confirmed post-mortem: added value of a decision tree approach.

Data from 204 participants from the Oxford Project to Investigate Memory and Ageing, who were diagnosed post-mortem using the histopathological criteria of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), were used to assess the validity of the clinical criteria for Alzheimer's disease (AD) of the 'National Institute of Neurological and Communicative Disorders and Stroke/the Alzheimer's Disease and Related Disorders Association' (NINCDS/ADRDA). Cases who had been diagnosed as NINCDS/ADRDA 'probable AD' in life were usually confirmed at autopsy, but half of the NINCDS/ADRDA 'negative' cases were not (low specificity). It was hypothesized that the overall clinical impression may have taken precedence over the use of the actual criteria. We therefore investigated the validity and reliability of the clinical criteria using a computerized 'dementia diagnosis system' for each of 6 sets of criteria [Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), NINCDS/ADRDA and three sets of criteria specifically for vascular dementia (VaD): NINCDS-AIREN, State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC), and Vascular Cognitive Impairment (VCI)] to classify a subset (n = 96) of the cases confirmed post-mortem. The use of the computerized system significantly (p = 0.01) increased the specificity (81%, similar to sensitivity) of the NINCDS/ADRDA diagnoses, which were shown to have 'moderate' inter-rater reliability. The DSM-IV criteria had good validity for AD when compared with post-mortem confirmation and showed 'substantial' inter-rater reliability. The ADDTC and VCI criteria for VaD had good specificity (88%) and sensitivity (75%), but only for one rater. The DSM-IV and NINCDS-AIREN criteria for VaD showed poor validity and inter-rater reliability. We conclude that the forced use of decision trees through a computerized system enhances the accuracy of the clinical diagnoses of dementia.

Aged↗
PubMed2003

Memory functions and focussed attention in middle-aged and elderly subjects are unaffected by a low, acute dose of caffeine.

The putative beneficial effects of caffeine on cognitive performance may vary between ages. The acute cognitive effects of 100 g caffeine on memory functions and focussed attention were investigated in sixteen middle-aged (45-60 years) and fourteen elderly (60-75 years) healthy men and women according to a cross-over design. Caffeine did not affect short-term memory span or speed, long-term memory retrieval functions or focussed attention. It is proposed that in middle-aged and elderly subjects cognitive effects may occur predominantly at higher caffeine dosages.

Aged↗
PubMed2002

Hormone replacement therapy for cognitive function in postmenopausal women.

BACKGROUND: As estrogens have been found in animal models to be associated with the maintenance and protection of brain structures, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by medication could be protective against cognitive decline. OBJECTIVES: To investigate the effect of ERT (estrogens only) or HRT (estrogens combined with a progestagen) in comparison with placebo in randomized controlled trials (RCTs) on cognitive function in postmenopausal women. SEARCH STRATEGY: The CDCIG Specialized Register was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* on 16 May 2002. In addition MEDLINE (1966-2002/01); EMBASE (1985-2000/11); PsycINFO (1967-2002/01) and CINAHL (1982-2001/12) were searched as the CDCIG Register does not contain all trials with healthy volunteers. SELECTION CRITERIA: All double-blind randomized controlled trials of the effect of ERT or HRT on cognitive function over a treatment period of at least two weeks in postmenopausal women. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the resulting lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. Two reviewers (EH and KY) assessed the quality of other aspects including design and assessment of outcomes. One reviewer (EH) extracted the data from the studies. MAIN RESULTS: In total, 15 trials involving 566 postmenopausal women were included, but 6 studies did not have adequate data for analysis. Meta-analyses showed a positive effect of 10 mg of estradiol (E2) bolus injections intramuscularly monthly in relatively young surgically menopausal women on the Paired Associate learning test immediate recall (z=2.40, p<0.05, chi-square test=1.12, p=0.29, SMD=1.02, 95% C.I.=0.19-1.85), on a test of abstract reasoning (z=10.45, p<0.0001, WMD=6.80, 95% C.I.=5.52-8.08) and a test of speed and accuracy (z=9.16, p<0.0001 WMD=6.00, 95% C.I.=4.72-7.28). However, most studies showed no evidence of an effect on verbal or visuospatial memory, mental rotations, speed or accuracy measures. There was little evidence that Premarin, the most widely prescribed estrogen for postmenopausal use, had positive effects on cognitive function. The one effect of 9 months of treatment with Premarin (and a progestagen) on a measure of complex speed of information processing (the TMT-B) was probably explained by baseline differences, as it was not reported by the authors. REVIEWER'S CONCLUSIONS: There was little evidence regarding the effect HRT or ERT on overall cognitive function in healthy postmenopausal women. There was an effect on some verbal memory functions (immediate recall), on a test of abstract reasoning and a test of speed and accuracy in relatively young (47 years of age) surgically menopausal women who had been given a bolus intramuscular injection of 10 mg E2 every month for 3 months. These effects were from small studies from a single research group. It remains to be determined whether factors such as an older age (> 69 years of age), type of menopause (surgical or natural) and type of treatment (E2 with or without a progestagen), mode of delivery (transdermal, oral or intramuscular), dosage and duration (> 3 months) could alter the effect on memory functions to a clinically relevant level. In addition, whether the absence or presence of menopausal symptoms can modify treatment effects should be investigated in more detail. Longitudinal RCTs currently underway in the U.S.A., U.K. and Canada will be able to test these hypotheses by the year 2010.

Cognition↗
PubMed2002

Hormone replacement therapy to maintain cognitive function in women with dementia.

BACKGROUND: As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline and the development of Alzheimer's disease (AD) or other dementia syndromes. OBJECTIVES: To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia. SEARCH STRATEGY: The CDCIG Specialized Register, which contains up-to-date records from many medical databases was searched using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen*, progesteron* and Alzheim* on 16th of May 2002. In addition, MEDLINE (1966-2002/01); EMBASE (1985-2002/01); and PsyINFO (1967-2002/01) were searched. SELECTION CRITERIA: All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia. DATA COLLECTION AND ANALYSIS: Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane. MAIN RESULTS: A total of five trials including 210 women with AD were analysed. Meta-analyses showed that there was a limited positive effect from low dosage of conjugated equine estrogens (CEE, 0.625 mg once a day) but not from higher dosage (1.25 mg of CEE once a day) on the Mini-Mental Status Examination after 2 months (WMD=1.28, 95% C.I.=0.26 to 2.30, z=2.45, p<0.01) and the effect disappeared after 3, 6 and 12 months of treatment. This effect was small and not clinically relevant as there was only a difference of 1 point on average in comparison with the placebo users (the scale range is 0-30). There were also short-term effects of 1.25 mg of CEE on tests of concentration and executive function, namely the Trail Making Test-B (WMD=-40.90, 95% C.I.-79.29 to -2.51, z=2.09, p<0.05) and Digit Span backward (WMD=0.67, 95% C.I.=-0.01 to 1.34, z=1.94, p<0.05). With regard to memory, only cued delayed recall of a word list was positively affected by 2 months of transdermal diestradiol (E2) (WMD=6.50, 95% C.I.=4.04 to 8.96, z=5.19, p<0.0001). No HRT effects were seen on other word lists, Paragraph Recall or Paired Associate Learning. In addition, no effects were seen on visual memory, language functions, most speeded tests, clinical rating scales or depression. Controls had better performance on the delayed recall of the Paragraph Test (overall WMD=-0.45, 95% C.I.=-0.79 to -0.11, z=2.60, p<0.01) after 1 month and on Finger Tapping after 12 months (WMD=-3.90, 95% C.I.=-7.85 to 0.05, z=1.93, p<0.05). Clinicians also gave controls a better score on a dementia rating scale (CDR, overall WMD=0.35, 95% C.I.=0.01 to 0.69, z=1.99, p<0.05). Positive findings in favour of treatment or placebo could have been random effects caused by multiple analyses. After correction for multiple testing, only the short-term positive treatment effect of E2 on memory remained. REVIEWER'S CONCLUSIONS: Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD. As we did not have data on women with other types of dementia (e.g. vascular dementia) this remains to be investigated. As most studies only used CEE and our earlier review in healthy women found effects only after a bolus injection of E2, it remains possible that different preparations or types of ERT or HRT could have a different effects. Several questions are raised in this review, including whether factors such as age, dementia onset (early AD), or the use of a particular preparation for a longer duration of treatment could have different effects. Perhaps the most important question is whether ERT or HRT can delay the time of onset of dementia. For answers to these questions, we have to await the results of the large RCTs currently in progress in the UK, USA, and Canada.

Cognition↗
PubMed2002

Apolipoprotein E epsilon4 and testosterone interact in the risk of Alzheimer's disease in men.

OBJECTIVES: To assess the association between testosterone levels and APOEepsilon4 in cases with AD and controls. METHOD: We included 61 men with definite or probable Alzheimer's disease (AD) and 55 elderly male controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA). Testosterone was measured using a competitive enzyme immunoassay (Bayer). RESULTS: We found that both low serum testosterone and the interaction between testosterone and APOEepsilon4 were associated with AD. Furthermore, testosterone levels were lower in APOEepsilon4-positive controls (mean: 11.3 nmol/L) than in controls without the allele (19.1 nmol/L). CONCLUSIONS: Low testosterone is potentially a modifiable risk factor, which may prove relevant to APOEepsilon4 carriers who are at risk of AD.

Aged↗
PubMed2001

A new visual rating scale for white matter low attenuation on CT.

The pathological substrate and clinical significance of white matter low density change on computed tomography (CT) remains incompletely understood, hampered by suboptimal rating scales. We developed a new scale and applied it to 647 CTs in 382 patients. White matter change was categorised by region (anterior and posterior frontal, parietal, occipital), severity (mild, moderate, severe) and extent (periventricular, extending to deep white, full thickness). Multiplying extent by severity gave regional scores, which were summated to give an overall score. CTs were read separately by 2 radiologists. Intraobserver reliabilities were 0.69 and 0.55, interobserver 0.70 (kappa values). Each assessment required only 1 min.

Brain↗
PubMed2001

Serum total testosterone is lower in men with Alzheimer's disease.

OBJECTIVES: The purpose of this study was to determine whether the level of serum total testosterone (TT) was different in cases of Dementia of the Alzheimer's Type (DAT) than in controls. SETTING AND DESIGN: We included 83 referred DAT cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford Project To Investigate Memory and Ageing. METHODS: Information was obtained about potential confounds in the relation of DAT with testosterone, including age, gender, education, body mass index, smoking, (ab)use of alcohol, diabetes mellitus, endocrine therapy, and having undergone hysterectomy. TT was measured in non-fasting serum obtained between 10 and 12 a.m. using a competitive enzyme immunoassay. RESULTS: Men with DAT (n=39) had lower levels (p =0.005) of total serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L). Lower TT was more likely in men with DAT, independent of potential confounds (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT levels between cases (n=44) and controls (n=62). MAIN FINDINGS: Our results suggested that low TT may be a co-morbid feature of DAT in men. However, low TT levels could also exacerbate the disease. CONCLUSIONS: Prospective longitudinal studies should investigate whether low TT levels precede or follow the onset of DAT (209 words).

Aged↗
PubMed2000

Habitual caffeine consumption and its relation to memory, attention, planning capacity and psychomotor performance across multiple age groups.

The present study evaluated the association between habitual caffeine intake via coffee and tea and cognitive performance. This was done as part of a larger research programme into the determinants of cognitive ageing (the Maastricht Aging Study: MAAS). Possible withdrawal effects that may have explained in part the positive association between performance and intake in an earlier study were controlled for. In addition, all cognitive tests in this study were administered under strict laboratory conditions. A group of 1875 healthy adults, stratified for age (range 24 - 81 years), sex, and general ability, were screened for habitual intake of coffee and tea and took part in extensive cognitive testing. Multiple regression analysis with control for age, sex, socio-demographic variables, and substance use showed that habitual caffeine consumption was significantly related to better long-term memory performance and faster locomotor speed. No relationships were found between habitual caffeine consumption and short-term memory, information processing, planning, and attention as measured with the Stroop Test. Moreover, no difference in sensitivity to caffeine intake between different age groups was found, suggesting that caffeine intake did not counteract age-related cognitive decline. Several recommendations are made to improve the design of future studies in this field. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis.

We reviewed epidemiological and experimental studies of female gonadal hormone replacement therapy (HRT) on cognitive function in post-menopausal women and carried out meta-analyses. In healthy ageing women, HRT has small and inconsistent effects that include enhancement of verbal memory, abstract reasoning and information processing. Epidemiological studies show larger effects than experimental studies, which is not related to sample size. Important confounds may be that women who start using HRT are healthier than women who do not. Also, controlling for socio-economic status diminishes the effect of HRT. The effects of HRT may depend on the age and type of menopause and the therapeutic intervention used, with the most widely used drug, Premarin, having least effect. However, the effects are independent of mood and climacteric symptom alleviation. There is a paucity of experimental studies that include healthy elderly women. The evidence for an estrogen deficiency in women with dementia and cognitive dysfunction is inconsistent. Nevertheless, epidemiological studies suggest that HRT protects against the development of clinically diagnosed Alzheimer's disease. However, poor recall of HRT use by patients and altered physician behaviour may have confounded the effects. Surprisingly, both healthy and demented women with low education seem to benefit most from HRT. Three recent controlled experimental studies using Premarin showed no effects of HRT in preventing further cognitive decline in women who already have Alzheimer's disease. Duration of treatment seems to play an important role, with beneficial effects declining-and even reversing-with longer treatment in women with Alzheimer's disease.Future research should further investigate the cognitive effect of different HRT preparations, serum estrogen levels, and the interactions of HRT with age, menopausal status and existing protective (e.g. education) and risk factors (e.g. smoking and apolipoprotein E genotype) for cognitive decline and Alzheimer's disease.

Age Factors↗
PubMed2000

Tryptophan depletion impairs memory consolidation but improves focussed attention in healthy young volunteers.

Animal and human studies have provided evidence for serotonergic modulation of cognitive processes. However, the exact nature of this relationship is not clear. We used the acute tryptophan depletion (ATD) method to investigate the effects of lowered serotonin synthesis on cognitive functions in 17 healthy young volunteers. The study was conducted according to a placebo-controlled, double-blind, crossover design. Cognitive performance and mood were assessed at baseline and 5 and 9 h after administration of ATD. A specific impairment of word recognition, without effects on short-term memory, occurred during ATD. No memory deficits were seen if ATD was induced after acquisition of new words. The Stroop Test and dichotic listening task demonstrated a modality independent improvement of focussed attention after ATD. Fluency was also improved after ATD. ATD did not alter speed of information processing, divided attention or planning functions. These results indicate that serotonin is essential in the process of long-term memory consolidation, primarily in the first 30 min after acquisition. Improvement of specific cognitive processes by lowered 5-HT function may be linked to the removal of inhibitory actions of 5-HT in the cortex.

Adult↗