Martin P. J. van Boxtel

Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised double blind, controlled trial

BACKGROUND Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the effect of folic acid on markers of atherosclerosis in men and women aged 50-70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the findings for the secondary endpoint: the effect of folic acid supplementation on cognitive performance. METHODS Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 mug daily oral folic acid or placebo for 3 years. The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency. Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604. FINDINGS Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (difference in Z scores 0.132, 95% CI 0.032 to 0.233), information processing speed (0.087, 0.016 to 0.158) and sensorimotor speed (0.064, -0.001 to 0.129) were significantly better in the folic acid group than in the placebo group. INTERPRETATION Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.

A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimers disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD‐I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre‐mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

The Stroop Color-Word Test Influence of Age, Sex, and Education; and Normative Data for a Large Sample Across the Adult Age Range

The Stroop Color-Word Test was administered to 1,856 cognitively screened, healthy Dutchspeaking participants aged 24 to 81 years. The effects of age, gender, and education on Stroop test performance were investigated to adequately stratify the normative data. The results showed that especially the speed-dependent Stroop scores (time to complete a subtest), rather than the accuracy measures (the errors made per Stroop subtask), were profoundly affected by the demographic variables. In addition to the main effects of the demographic variables, an Age Low Level of Education interaction was found for the Error III and the Stroop Interference scores. This suggests that executive function, as measured by the Stroop test, declines with age and that the decline is more pronounced in people with a low level of education. This is consistent with the reserve hypothesis of brain aging (i.e., that education generates reserve capacity against the damaging effects of aging on brain functions). Normative Stroop data were established using both a regression-based and traditional approach, and the appropriateness of both methods for generating normative data is discussed.

Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies

Dementia has a multifactorial etiology, but the importance of individual health and lifestyle related risk factors is often uncertain or based on few studies. The goal of this paper is to identify the major modifiable risk factors for dementia as a first step in developing an effective preventive strategy and promoting healthy late life cognitive functioning.

The concept shifting test : Adult normative data

The Concept Shifting Test (CST) is a newly developed Trail Making Type test that measures concept shifting and executive functioning. The purpose of the present study was to determine whether CST performance was affected by age, gender, educational level, or handedness and to establish the normal range of test performance. The CST was administered to a large sample (N = 1,794) of cognitively intact adults (age range 24 to 81 years). The results showed that CST performance was superior in women, decreased with age, and increased with level of education. Handedness did not affect CST performance. Normative data that are corrected for the influences of these demographical variables were established with a regression-based normative approach.

Efficacy and usability of assistive technology for patients with cognitive deficits: a systematic review

Objective: To determine the efficacy of portable electronic aids such as personal digital assistants (PDAs), pagers or mobile phones for patients with cognitive deficits by means of a systematic review. The usability of these aids is also briefly discussed. Data sources: PubMed, CINAHL, PsychINFO, EMBASE and MEDLINE were searched up to February 2009. The references of identified and relevant articles were scanned to find additional relevant titles. Review methods: Papers referring to ‘electronic aids’, ‘cognition’ and ‘brain injury’ were included. The population had to be adult and have cognitive impairments as a result of acquired brain injury. Outcome measures were change in cognitive or occupational performance or the level of participation in daily life. The criteria of Cicerone et al. were used to evaluate the quality of the retrieved studies. Results: Twenty-eight papers presenting 25 studies were reviewed. The total number of participants was 423. Most identified papers described case reports or non-randomized clinical trials. Only one randomized controlled trial was identified, in which the NeuroPage proved effective in supporting prospective memory. Other kinds of assistive technology such as PDAs and voice recorders showed positive results in supporting retrospective and prospective memory. Conclusion: The efficacy of assistive technology in general is not yet sufficiently studied in randomized controlled trials, although promising results has been reported. Furthermore, several survey studies established that both potential users and clinicians have optimistic expectations about the usability of assistive technology.

Mental work demands protect against cognitive impairment: MAAS prospective cohort study.

Little is known about whether persons with mentally demanding jobs are protected against cognitive impairment and whether this association is independent of intellectual abilities and other confounders. Longitudinal data from the Maastricht Aging Study (MAAS) were used to examine this association. After the 1993-1995 baseline examination, there was a first 3-year follow-up examination (1996-1998) among 630 men and women, aged 50 to 80, who exhibited no cognitive impairment at baseline. Persons with mentally demanding jobs had lower risks of developing cognitive impairment during follow-up (36 cases), compared with persons without such jobs (odds ratio = 0.79; 95% confidence interval: 0.65-0.96). About 1.5% of the persons with high mental work demands developed impairment compared to 4% of the persons with few work demands. The protective effect was independent of intellectual abilities and other confounders. Our findings provide evidence that continued and potentially modifiable mental stimulation during adult life may protect men and women against cognitive impairment.

Engaged lifestyle and cognitive function in middle and old-aged, non-demented persons: a reciprocal association?

Summary. Some studies have shown that cognitive function is positively affected by an engaged and active lifestyle. However, a recent study found evidence for an opposite causal direction, i.e., persons with good cognitive function more often start to engage in leisure-time activities. Here, we longitudinally examine the causal direction of the association between an engaged lifestyle and cognitive function in middle and old-aged Dutch men and women.    The participants in the prospective cohort study “Maastricht Aging Study” (MAAS) were recruited from a register of 15 family practices in the South of the Netherlands. There were 830 non-demented men and women, aged 49 to 81 in 1993–1995 (baseline phase). They were re-examined three years later (follow-up phase). During both phases, all persons reported on their participation in mental, social, and physical activities. Six separate neuropsychological tests, including the Mini-Mental State Examination, were used to define cognitive function at baseline and follow-up.    All three activities measured were negatively related to cognitive decline between both phases. Effects were moderate, but consistent. Persons participating in all three activities were particularly protected against longitudinal decline. Furthermore, persons with the best baseline cognitive performance were more likely to increase their number of activities during follow-up compared with persons with the poorest scores.    In summary, an engaged lifestyle and cognitive function mutually influence each other in middle and old aged, non-demented persons. This reciprocal association is characterized by simultaneous positive effects of leisure-time activities and good cognitive function on cognitive function and leisure-time activities, respectively. This reciprocal association may create a self-reinforcing, beneficial or adverse life-course in middle and old age.Zusammenfassung. Verschiedene Untersuchungen haben ergeben, dass ein engagierter Lebensstil die kognitive Funktion positiv beeinflusst. Jedoch, eine rezente Untersuchung hat eine entgegengesetzte kausale Richtung dargestellt, d.h. dass Personen, die gut kognitiv funktionieren, häufiger und früher Freizeitaktivitäten entwickeln. In dieser Studie haben wir den kausalen Zusammenhang zwischen einem aktiven Lebensstil und der kognitiven Funktion bei älteren und alten niederländischen Männern und Frauen erforscht.   Für diese prospektive Kohorten-Untersuchung „Maastricht Aging Study (MAAS)“ entnahmen wir die Teilnehmernamen einem ärztlichen Register von 15 Praxen im Süden der Niederlande. In den Jahren 1993–1995 untersuchten wir 830 nicht-demente Männer und Frauen im Altersbereich von 49–81 Jahren (erste Phase). Nach drei Jahren wurde die Untersuchung wiederholt (zweite Phase). In beiden Phasen wurden die Personen um ihre mentalen, sozialen und physischen Aktivitäten befragt. Damit das kognitive Funktionieren in der ersten und zweiten Phase festgestellt werden konnte, verwendeten wir sechs unterschiedliche neuropsychologische Tests, einschließlich der Mini Mental State Examination.    Die drei untersuchten Aktivitäten beeinträchtigten, jede für sich die kognitive Leistung zwischen den beiden Phasen. Die Effekte waren zwar bescheiden, aber konsistent. Die Personen, die alle drei Aktivitäten ausübten, waren besonders vor kognitiver Beeinträchtigung geschützt. Die Personen, die ihre Aktivitäten zwischen der ersten und zweiten Phase erweitern, waren auch diejenigen, die in der ersten Phase am besten kognitiv funktionierten.    Kurz gefasst, ein aktiver Lebensstil und die kognitive Funktion beeinflussen sich bei nicht dementen Personen mittleren und höheren Alters gegenseitig und im positiven Sinne. Diese reziproke Assoziation wird durch simultane, positive Effekte von Freizeitaktivitäten auf die kognitive Funktion einerseits, und von der kognitiven Funktion auf die Freizeitaktivitäten andererseits charakterisiert. Diese reziproke Assoziation kann bewirken, dass sich – sich selbst verstärkend – ein positiver oder aber ungünstiger Lebensverlauf in mittlerem und höherem Alter entwickelt.

Associations between lifestyle and depressed mood: Longitudinal results from the Maastricht Aging Study

OBJECTIVES We examined whether healthy lifestyles are associated with absence of depressed mood. METHODS A sample of 1169 adult participants in the Maastricht Aging Study provided baseline and 6-year follow-up data on smoking, alcohol use, physical exercise, body mass index, and mood. We examined associations between lifestyles and depressed mood using longitudinal analyses controlling for baseline depressive symptoms and covariates. RESULTS Reports of excessive alcohol use at baseline predicted depressed mood at follow-up (relative risk [RR] = 2.48; 95% confidence interval [CI] = 1.08, 5.69), and reports of more than 30 minutes of physical exercise per day at baseline were associated with an absence of depressed mood at follow-up (RR=0.52; 95% CI=0.29, 0.92). Reports of being engaged in physical exercise throughout the 6-year follow-up period were also associated with absence of depressed mood (RR=0.56; 95% CI=0.34, 0.93). CONCLUSIONS In this relatively healthy population sample, certain lifestyles either predicted or protected against depressed mood. Adopting or maintaining healthy lifestyles might be a starting point in preventing or treating depressed mood over time.

Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study

To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43-70 years at baseline (1995-2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.