Ageing

What are the changes we see in the ageing brain?

• Atrophy: reduction in brain tissue, both grey and white matter. Increase in the size of the ventricles and sulci
• White matter hyperintensities (WMH): also called lesions or white matter lesions. Visible as bright white areas in the white matter on certain MRI scans
• Loss and death of neuronal circuits: in particular hippocampal and neocortical circuits

Which cognitive abilities change in ageing?

• Working memory
• Long-term memory
• Short-term memory
• Verbal knowledge
• Attention

Frontal Executive Hypothesis: executive function is a primary deficit in ageing. It's associated with a decline of grey matter in the frontal lobes. Evidence from lesion studies and functional imaging show that the frontal lobes are important for executive function. Executive function declines with age, and may be greater than other cognitive declines. However, there is evidence for other brain regions involved in executive function

Disconnection Hypothesis: refers to disconnection between brain regions. Often white matter damage disrupts communication between brain regions - leads to a decline in function and cognition. White matter damage has been shown to effect cognition in: multiple sclerosis and small vessel disease. There is evidence for white matter damage in ageing - white matter hyperintensities which increase with age. However it is too simple to just observe how much "damage" is visible, we must consider to what extent the integrity of the structure is damaged.

These theories may not be mutually exclusive; the frontal lobes are very well connected to the rest of the brain. Grey matter and white matter are also connected and influence each other.

• Cardiovascular risk factors: hypertension, diabetes, high cholesterol, smoking, obesity, physical inactivity
• Genetic factors(non-modifiable)
• Capacity for plasticity 
• Age(n-m)
• Sex(n-m)
• Family history(n-m)

Hypertension increases relative risk of deep white matter hyperintensities and periventricular white matter hyperintensities. Associated with risk of stroke

Vascular dementia: cognitive abilities effected are - executive function, attention and processing speed. Stages are small vessel disease and then non=amnesic mild cognitive impairment

Alzheimer's Disease: cognitive abilities effected are episodic memory. Stage is amnesic mild cognitive impairment.

Risk factors associated with dementia

• Age
• Genetics
• Sex
• Ethnicity
• Smoking
• Health
• Diet
• Exercise
• Depression

Cerebral small vessel disease covers a variety of abnormalities related to small blood vessels in the brain. Affected functions are executive functions, attention, speed of information processing, episodic memory, and visuo-spatial abilities. Other problems associated with SVD are:

• Cogntive impairment: several studies have found that cerebral SVD is correlated with worse scores on the mini-mental state exam (van der Flier et al, 2005)
• Problems with walking or balance: white matter lesions have been repeatedly associated with gait disturbances and mobility difficulties (Callisaya et al, 2013)
• Strokes: white matter hyperintensities are associated with a more than two-fold increase in the risk of stroke (Debette & Markus, 2010)
• Depression: white matter changes have been associated with a higher risk of depression in older people (Herrmann, Le Masurier, Ebmeier, 2008)
• Other dementias: cerebral SVD associated with an increased risk or severity of other forms of dementia such as Alzheimer's disease (Gorelick et al, 2011)

Vascular dementia is the 2nd most common type of dementia after Alzheimer's disease. Symptoms include memory loss, and difficulties with thinking, problem-solving or language. These symptoms occur when the brain is damaged because of problems with the supply of blood to the brain. Damage is visible on MRI/CT. 

20% of strokes are Transient Ischaemic Attack (TIA)/ mini-stroke. They are the most common cause of vascular dementia, and a major cause of non-dementia cognitive impairment.

Cardiovascular risk factors and stroke lead to cognitive difficulties. White matter damage is observed and progresses. Executive functions are particularly effected

Alzheimer's is the most common form of dementia. Prevalence increases with age, and the disease is progressive and incurable. Memory, language, visuo-spatial skills, concentration and orientation are affected.

Risk factors

• Age
• Genetics
• Comorbid cardiovascular disease

Atrophy of hippocampal formation well described; atrophy is 2.5x greater in patients with Alzheimer's than controls (Jack et al, 1998). Both grey and white matter affected.

Plaques and tangles are thought to be prime suspects in cell death and tissue loss in the Alzheimer brain. Plaques are abnormal clusters of proteins that build up between nerve cells. Small clumps of plaques may block cell-to-cell signalling at synapses. Tangles form in dying cells. They are twisted fibres of a protein called tau. Twisted strands of tau essentially disintegrate the transport system so nutrients can no longer move through cells.