The Ageing Brain Fergus Doubal October 2007

Plan Age is a case of mind over matter – if you don’t mind it doesn’t matter (Wilde) What matters most is function Then structure – largely studied with MRI Then functional imaging, cortical plasticity etc Defining normal ageing difficult

Questions Forget science and evidence etc. What do you think happens in normal ageing – to your granny, to your patients? In your practice, what happens to brains on CT scans as age increases?

Fergus’ answers Become slightly forgetful – ie forget where they put things, peoples names, perhaps unable to work new things eg remote controls Brains seem to shrink on CT or rather on the ocasional young persons CT you see there seems to be quite a lot of brain (MCA)

Cognitive Function and Age

Cognition 1. Crystallised intelligence 2. Memory – short and long term Cumulative end product of information acquired – vocab, knowledge based 2. Memory – short and long term 3. Cognitive speed – timed performance on perceptual tasks eg digit symbol subtraction

Canberra Longitudinal Study 10 years of testing old people 1. Crystallised intelligence – unchanged 2. Memory – decreases with age 3. Cognitive speed – decreases with age

What causes this decline? Predictive factors are: Education level, High blood pressure Poor health Presence of APOE E4 allele ANZ J Psych. 2001 35:768-775

Brain Imaging Brain size (volumetric or scales) White matter disease (volumetric or scales) All on MRI

The Framingham Study for brain ageing changes Currently consists of 2 cohorts – the original 1948 (5,000) and their offspring (5,000) Predominately white middle class Follow up ongoing 2,000 had brain MRI (cross sectional study) Looked at regional brain volume, WMH and silent infarcts (those w neurol d excl)

Findings Men had bigger brains than women (but not after correction) Before 50 age did not affect brain size After 50, age explained 50% of volume loss – frontal and temporal lobes affected the most. No differences between men and women Infarcts unsurprisingly assoc w volume loss

Brain atrophy Can be measured with scale (0-4) or volumetrically

Neurobiology of Aging Information Center 2% reduction in weight/volume per decade Not due to neronal loss but shrinkage Frontal lobe affected in normal ageing Hippocampus (and perhaps different areas within the HC) affected in AD – mention dentate gyrus and entorhinal cortex

WMH Seen as hyperintensities on T2 MRI Common Assoc w hypertension, Assoc w cognitive function Progress w age – best predictor is baseline WMH Assoc w lacunar stroke and cerebral microhaemorrhages Fine when looking at path etc but how do they relate to individual patients Could they be used as a surrogate marker for trials in vasc cognitive impariment

WMH – non confluent

WMH – confluent

Neurobiology of Aging Information Center Connections – decrease, may account for cognitive slowing ACh and dopamine decrease w age But brain retains plasticity – ability to make new connections after insult as seen with stroke and then devastaing effects of bilateral strokes

Summary Crystallized intelligence remains Memory and cognitive speed decrease Brains shrink w regional variation White matter hyperintensities increase. To relate back –your granny will become more forgetful and her brain will shrink