Physical and Mental Coordination in the Elderly: A Causal Role for the Cerebellum?

The mechanisms underlying the progressive changes in tissues and organs that characterise normal ageing remain unclear. The cerebellum is known to play a major role in motor function, but recent research suggests it plays an equivalent role in cognition. Working with the hypothesis that cortico-cerebellar loops ensure smooth and coordinated activity in both domains, this thesis investigates the possible role of the cerebellum in normal ageing and in interventions to improve function, seeking to contribute to both theoretical and applied approaches to ageing. Study one investigated relationships between motor and cognitive function using raw data from a national normative sample of adults aged 16 to 75, employing a test battery assessing motor and cognitive skills. Differences between age groups were demonstrated in some tests of complex processing speed, working memory and executive function, with suggestive evidence that senescence in tests is reflected in tests sensitive to cerebellar function. Study two refined the battery, while including further measures of motor and memory performance to investigate linkages between cognitive and cerebellar function. Using a sample of 256 older adults, results were variable but provided evidence that pegboard performance could act as a predictor of some cognitive functions. Study three investigated a proactive intervention for healthy older adults designed to improve cerebellar function, and therefore balance and executive function. This involved an 8-10 week self-administered, internet-based coordinative exercise intervention using a ‘cerebellar challenge’ suite of graded activities. Performance on a basket of tests was assessed before and after, and also compared with performance changes in a no-intervention control group. Significantly greater benefits for the intervention group than the controls were found for balance physical coordination and controlled information processing. Overall, these studies support current research indicating cerebellar contribution to both cognitive and motor problems arising in old age, and present evidence that non-verbal memory and controlled speeded information problems may be alleviated through targeted activities affecting cerebellar function improving postural stability and physical coordination

"Cerebellar Challenge" for Older Adults: Evaluation of a Home-Based Internet Intervention

There is converging evidence that maintenance of function in the multiple connectivity networks involving the cerebellum is a key requirement for healthy aging. The present study evaluated the effectiveness of a home-based, internet-administered “cerebellar challenge” intervention designed to create progressive challenges to vestibular function, multi-tasking, and dynamic coordination. Participants (n = 98, mean age 68.2, SD 6.6) were randomly allocated to either intervention (the cerebellar challenge training for 10 weeks) or no intervention. All participants undertook an initial series of pre-tests, and then an identical set of post-tests following the intervention period. The test battery comprised five suites of tests designed to evaluate cognitive-sensori-motor-affective functions, including Physical Coordination, Memory, Language Dexterity, Fluid Thinking and Affect. The intervention group showed significant pre- to post improvements in 9 of the 18 tests, whereas the controls improved significantly on one only. Furthermore, the intervention group showed significantly greater improvement than the controls on the “Physical Coordination” suite of tests, with evidence also of differential improvement on the Delayed Picture Recall test. Frequency of intervention use correlated significantly with the improvement in balance and in peg-moving speed. It is concluded that an internet-based cerebellar challenge programme for older adults can lead to benefits in balance, coordination and declarative memory. Limitations and directions for further research are outlined

Digital mammographic density and breast cancer risk:a case-control study of six alternative density assessment methods

INTRODUCTION: Mammographic density is a strong breast cancer risk factor and a major determinant of screening sensitivity. However, there is currently no validated estimation method for full-field digital mammography (FFDM). METHODS: The performance of three area-based approaches (BI-RADS, the semi-automated Cumulus, and the fully-automated ImageJ-based approach) and three fully-automated volumetric methods (Volpara, Quantra and single energy x-ray absorptiometry (SXA)) were assessed in 3168 FFDM images from 414 cases and 685 controls. Linear regression models were used to assess associations between breast cancer risk factors and density among controls, and logistic regression models to assess density-breast cancer risk associations, adjusting for age, body mass index (BMI) and reproductive variables. RESULTS: Quantra and the ImageJ-based approach failed to produce readings for 4% and 11% of the participants. All six density assessment methods showed that percent density (PD) was inversely associated with age, BMI, being parous and postmenopausal at mammography. PD was positively associated with breast cancer for all methods, but with the increase in risk per standard deviation increment in PD being highest for Volpara (1.83; 95% CI: 1.51 to 2.21) and Cumulus (1.58; 1.33 to 1.88) and lower for the ImageJ-based method (1.45; 1.21 to 1.74), Quantra (1.40; 1.19 to 1.66) and SXA (1.37; 1.16 to 1.63). Women in the top PD quintile (or BI-RADS 4) had 8.26 (4.28 to 15.96), 3.94 (2.26 to 6.86), 3.38 (2.00 to 5.72), 2.99 (1.76 to 5.09), 2.55 (1.46 to 4.43) and 2.96 (0.50 to 17.5) times the risk of those in the bottom one (or BI-RADS 1), respectively, for Volpara, Quantra, Cumulus, SXA, ImageJ-based method, and BI-RADS (P for trend <0.0001 for all). The ImageJ-based method had a slightly higher ability to discriminate between cases and controls (area under the curve (AUC) for PD = 0.68, P = 0.05), and Quantra slightly lower (AUC = 0.63; P = 0.06), than Cumulus (AUC = 0.65). CONCLUSIONS: Fully-automated methods are valid alternatives to the labour-intensive "gold standard" Cumulus for quantifying density in FFDM. The choice of a particular method will depend on the aims and setting but the same approach will be required for longitudinal density assessments