T.J.M. van der Cammen

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study

Abstract Objective: To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. Design: Population based cross sectional study. Setting: Ommoord, a suburb of Rotterdam. Subjects: 7528 participants of the Rotterdam study aged 55-106 years. Results: 474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimers disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinsons disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. Conclusions: The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimers disease. In this study an inverse dose-response relation was found between education and dementia—in particular, Alzheimers disease. Key messages Key messages Of all cases of dementia, 72% were cases of Alzheimers disease The pronounced increase in prevalence of dementia with age was due to a substantial increase in Alzheimers disease Alzheimers disease was more often diagnosed in less educated people The association between dementia and education could not be explained by cardiovascular disease comorbidity

Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease

Background/Aims: Recent studies suggest that vitamin D metabolites may be important for preserving cognitive function via specific neuroprotective effects. No large studies have examined the association between vitamin D status and cognition. Methods: In this cross-sectional study, we analyzed the serum 25-hydroxyvitamin D3 levels and Mini-Mental State Examination (MMSE) test scores of 225 older outpatients who were diagnosed as having probable Alzheimer’s disease (AD). In addition to the 25-hydroxyvitamin D3 levels, we analyzed the serum vitamin B1, B6 and B12 levels. Results: An association was found between MMSE test scores and serum 25-hydroxyvitamin D3 levels, with a β-coefficient of 0.05 (p = 0.01). Vitamin-D-sufficient patients had significantly higher MMSE scores as compared to vitamin-D-insufficient ones. No association was found with the other serum vitamin levels. Conclusions: These data support the idea that a relationship exists between vitamin D status and cognition in patients with probable AD. However, given the cross-sectional design of this study, no causality can be concluded. Further prospective studies are needed to specify the contribution of vitamin D status to the onset and course of cognitive decline and AD.

The diagnostic value of SPECT with Tc 99m HMPAO in Alzheimer's disease: A population‐based study

We studied the diagnostic accuracy of single-photon emission computed tomography (SPECT) with technetium 99m-labeled hexamethylpropylene amine oxime (Tc 99m HMPAO) in 48 patients with probable Alzheimers disease (AD) according to NINCDS-ADRDA criteria and in 60 controls recruited from a population-based study. With logistic regression, we identified decreased temporal regional cerebral blood flow as the best discriminating variable between patients and controls. Receiver-operator characteristic curves showed that the discriminative ability of SPECT improved with increasing dementia severity. With specificity set at 90%, sensitivity figures were 42% in mild, 56% in moderate, and 79% in severe AD. The diagnostic gain as a function of the prior probability of the disease being present was computed for those with mild AD. When the prior probability varied at around 50%, the diagnostic gain for mild AD patients was substantial (a maximum of 34%) for a positive test result but poor for a negative test result. The results suggest that the practical usefulness of SPECT as a diagnostic adjunct in patients suspected of having mild AD is confined to situations in which, on clinical grounds, there is considerable diagnostic doubt.

Abnormal amino acid metabolism in patients with early stage Alzheimer dementia

Summary. Plasma levels of several amino acids were studied in 14 patients with early stage probable Alzheimers disease (AD) and 17 age-matched controls. In the AD patients a possible relationship between amino acid levels and behavioural symptomatology was also investigated. We found significantly reduced levels of tryptophan and methionine in plasma samples from the AD patients compared to the control subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and the ratio of plasma taurine and the product of the plasma levels of methionine and serine (TSM-ratio) were significantly increased in the AD patients in comparison with the controls. However, no difference was found in plasma tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning the behavioural symptomatology no significant correlation was found between the Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported findings suggest that abnormal amino acid metabolism is present in the early stages of AD. We hypothesize that this abnormality could play a role in the pathogenesis of behavioural changes occurring in later stages of AD.

Results of 2-year vitamin B treatment on cognitive performance; Secondary data from an RCT

Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels. Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721). Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval −5.3 to −4.7) µmol/L in the B-vitamin group and 1.3 (−1.6 to −0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (−0.2 to 0.0) in the B-vitamin group and 0.3 (−0.4 to −0.2) in the placebo group (p = 0.05), as determined by an independent t test. Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance. Classification of evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.

Predictors of falls in elderly people during rehabilitation after hip fracture--who is at risk of a second one?

Summary.Background: A fall in old age is known as a common consequence of frailty and decline as well as a risk factor for further falls. Studies identifying hip fracture patients who are at risk of a further fall are lacking. Therefore it was of interest to evaluate the risk factors for falling in a high-risk population, i.e., patients during rehabilitation after recent proximal femur fracture. Methods: 935 consecutive patients who had surgical intervention after acute fracture of the proximal femur underwent a multidimensional assessment within the first two days after admission to the rehabilitation ward. Falls during the stay on the rehabilitation ward were registered. The baseline data were compared between fallers and non-fallers. Findings: 11.8% of the patients fell during rehabilitation. Risk factors associated with a fall were increasing age, male gender, type of surgery, the use of a rollator and nocturnal urinary incontinence. The risk of falling increased in the middle of the second week of rehabilitation, when frailer patients gained mobility and ability to walk by themselves, while they were not yet safe enough. Interpretation: It was possible to compose a risk profile for future falls. Those identified as ’at risk of a further fall‘ should be selectively offered protective devices and special training programs in order to prevent future fractures. As for the surgical intervention, the type of surgery in relation to age and long-term outcome is of particular interest since the use of the more expensive total hip arthroplasty procedure may be more cost effective in the long term.Zusammenfassung.Hintergrund: Stürze sind bekannte Folgen von allgemeiner Schwäche und Gebrechlichkeit älterer Menschen, gleichzeitig aber auch der wichtigste Risikofaktor für einen weiteren Sturz. Es fehlen Studien, die das Sturzrisiko von Patienten nach Schenkelhalsfraktur evaluieren. Deshalb wurden Patienten im Rahmen der Rehabilitation nach hüftgelenksnaher Femurfraktur bezüglich ihres weiteren Sturzrisikos evaluiert. Patienten und Methode: Es wurden 935 Patienten nach chirurgischer Sanierung einer hüftgelenksnahen Femurfraktur im Rahmen der Aufnahmeuntersuchung zur Rehabilitation im Sinne eines multidimensionalen Geriatrischen Assessment untersucht. Die Stürze während der Rehabilitation wurden exakt dokumentiert und die Basisdaten des Assessments zwischen „Stürzern“ und „Nicht-Stürzern“ verglichen. Ergebnisse: 11,8% der Patienten stürzten während der Rehabilitation. Als spezielle Risikofaktoren konnten das Alter per se, das männliche Geschlecht, der Bedarf eines Rollators und nächtliche Inkontinenz identifiziert werden. Das Sturzrisiko nahm während der zweiten Woche signifikant zu. Bei zunehmender Mobilität, ohne gleichzeitige Sicherheit, stieg das Sturzrisiko insbesondere für die gebrechlichen Patienten. Diskussion: Im Rahmen der Studie konnte ein besonderes Risikoprofil in dieser Hochrisikogruppe identifiziert werden. Jenen Patienten sollte während der Rehabilitation spezielle Trainingsprogramme und protektive Maßnahmen angeboten werden, um eine weitere Fraktur zu verhindern. Gleichzeitig bedarf es weiterer Studien, um den Einfluss der verwendeten Osteosynthese auf das Sturzrisiko zu überprüfen.

Assessment of cerebral perfusion with single-photon emission tomography in normal subjects and in patients with Alzheimer's disease: effects of region of interest selection

The shape, size and location of regions of interest (ROls) show considerable variability between single-photon emission tomography (SPET) studies in aging and Alzheimers disease, but the possible influence on study results remains unknown. We compared three different ROIs in a SPET study with 60 controls and in 48 patients with probable Alzheimers disease diagnosed according to the NINCDS-ADRDA criteria. Regional cerebral blood flow (rCBF) was assessed with SPET using technetium-99m d,l-hexamethylpropylene amine oxime (99mTc-HMPAO), normalized to the mean activity in a cerebellar reference slice. The three different ROIs were: a multi-slice and a single-slice ROI with reference to the normal brain anatomy (using an anatomical atlas), and a rectangular (2×4 pixels) ROI in the frontal, temporal, temporoparietal and occipital cortices. No differences were observed for the means of rCBF values between the single-slice and multi-slice ROIs with reference to the normal anatomy, but some variability was present for individual comparisons. In contrast, significantly higher mean rCBF values were obtained with the single-slice rectangular ROls in all four regions for both patients and controls and considerable variability was shown for individual subjects. After analysis with multivariate logistic regression and receiver operator characteristic curves, the ability of SPET to discriminate between controls and Alzheimer patients was similar in the three methods for mild and moderate Alzheimer patients (Global Deterioration Scale = GDS of 3 and 4). However, with increasing dementia severity (GDS>4) the rectangular ROIs showed lower ability to discriminate between groups compared to the singleslice and multi-slice anatomically defined ROIs. This study suggests that results of rCBF assessment with SPET using 99mTc-HMPAO in patients with severe Alzheimers disease are influenced by the shape and size of the ROI.

Risk of Left Ventricular Dysfunction in Patients with Probable Alzheimer's Disease with APOE*4 Allele

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimers disease (AD) patients.

The association between plasma homocysteine levels and bone quality and bone mineral density parameters in older persons

INTRODUCTION High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters, rather than with bone mineral density. METHODS Cross-sectional data of the B-PROOF study (n=1227) and of two cohorts of the Rotterdam Study (RS-I (n=2850) and RS-II (n=2023)) were used. Data on bone mineral density of the femoral neck and lumbar spine were obtained in these participants using dual-energy X-ray assessment (DXA). In addition, participants of B-PROOF and RS-I underwent quantitative ultrasound measurement of the calcaneus, as a marker for bone quality. Multiple linear regression analysis was used to investigate the associations between natural-log transformed plasma levels of homocysteine and bone mineral density or ultrasound parameters. RESULTS Natural-log transformed homocysteine levels were inversely associated with femoral neck bone mineral density in the two cohorts of the Rotterdam Study (B=-0.025, p=0.004 and B=-0.024, p=0.024). In B-PROOF, no association was found. Pooled data analysis showed significant associations between homocysteine and bone mineral density at both femoral neck (B=-0.032, p=0.010) and lumbar spine (B=-0.098, p=0.021). Higher natural-log transformed homocysteine levels associated significantly with lower bone ultrasound attenuation in B-PROOF (B=-3.7, p=0.009) and speed of sound in both B-PROOF (B=-8.9, p=0.001) and RS-I (B=-14.5, p=0.003), indicating lower bone quality. Pooled analysis confirmed the association between homocysteine and SOS (B=-13.1, p=0.016). Results from ANCOVA-analysis indicate that differences in SOS and BUA between participants having a plasma homocysteine level above or below median correspond to 0.14 and 0.09 SD, respectively. DISCUSSION In this study, plasma levels of homocysteine were significantly inversely associated with both bone ultrasound parameters and with bone mineral density. However, the size of the associations seems to be of limited clinical relevance and may therefore not explain the previously observed association between plasma homocysteine and osteoporotic fracture incidence.

Automatic registration of falls and other accidents among community dwelling older people: feasibility and reliability of the telephone inquiry system

Introduction and purpose The longitudinal registration of accidents, including falls, among people aged 65 and older is both time-consuming and expensive. For this reason, a computerised method for telephone accident registration, ‘Telephone Inquiry System (TIS)’, was developed and its feasibility (participation, successful dialogues) and reliability (distribution of accidents regarding location, falls requiring medical attention, and falls resulting in fractures) were evaluated. Method The TIS is an Interactive Voice Response computer system by which people are telephoned and asked about involvement in accidents and falls in a structured automatic dialogue. If people reported involvement in an accident, details about the circumstances were asked personally by telephone. It was tested in two prospective follow-up studies among community dwelling older people aged 65 and older in the Netherlands between 1994 and 2003. Results Of the 3,500 and 8,650 people invited to participate in the two studies, 30.1% and 24.0% did, respectively. In total, the TIS made 48,966 attempts to have an automatic dialogue with respondents, of which more than 70% were successful. Sixty percent of the accidents happened in and around the home. Twenty-five percent of the falls required medical attention and at least 3.3% resulted in a fracture. Conclusions The TIS appears to be a feasible and reliable method for semi-automatically registering accidents among community dwelling older people. Valid comparison of data between countries and communities is made possible because the registration is not influenced by differences in patient flows and the questions and procedures are highly standardised. Automatic regisration of falls 25