Article 5: INSIGHTS INTO THE AGEING MIND: A VIEW FROM COGNITIVE NEUROSCIENCE (Hedden, Gabrieli)

Question 1

intro

Answer 1

• contrasting patterns of decline and stability in cognition across the adult lifespan
• robust declines in encoding new memories of episodes or facts, working memory (the simultaneous short-term maintenance and manipulation of information involving EXECUTIVE PROCESSES) and processing speed (the speed with which information can be processed)
• short-term memory (a component process of working memory),autobiographical memory, semantic knowledge and emotional processing remain relatively stable

Question 2

Behavioral research

Answer 2

• although ageing might have global effects, it influences certain cognitive functions disproportionately

Question 3

Life-long declines

Answer 3

• basic mechanisms of cognitive information processing:
processing speed,
working memory and
encoding of information into episodic memory
 BUT different results for cross-sectional and longitudinal studies:
Cross-sectionalprocessing speed, working memory and episodic memory showed linear life-long declines with little or no evidence for accelerated decline in the later decades
Longitudinal age-related changes from age 20 to 60 tend to be small or non-existent, with speed of processing showing the largest change, whereas changes after the age of 60 have a slope that is roughly equivalent to that found in cross-sectional data.
• acceleration of cognitive decline that begins 3–6 years before death

Question 4

Late-life declines

Answer 4

• no decline for well-practiced tasks, tasks that involve knowledge until late life
• short term memory (phonological storage, digit span): sharp decline after 70
• vocabulary and semantic knowledge also stable until later life
• life experienceknowledgewisdom

Question 5

Life-long stability

Answer 5

•	Autobiographical memory, 
emotional processing and 
automatic memory processes 
seem to be unchanged throughout life
•	ToM
•	automatic feelings of familiarity continue to be relied on even when effortful recollection fails with age

Question 6

Age-related neural changes

Answer 6

• brain: lower volumes of grey matter result not from cell death, but rather from lower synaptic density
• PFC and medial temporal structures especially affected
• Occipital cortex relatively unaffected

Question 7

Normal and pathological ageing

Answer 7

• changes in the FRONTOSTRIATAL SYSTEM, with decreases in dopamine (!), noradrenaline and serotonin, and declines in the volume and function of the PFC, changes in white matter
normal ageing
• loss of volume in entorhinal cortex (relay between the hippocampus and association cortices)
Alzheimer’s (MCI first)

Question 8

PFC and striatal circuits

Answer 8

• Theory: prefrontal deficits were the underlying cause of cognitive ageing
• PFC: largest age-related volumetric changes in adulthood
• In healthy older adults, the largest declines in volume are in lateral regions of the PFC. By contrast, patients with Alzheimer’s disease show the greatest degeneration in the inferior PFC, although deterioration of the PFC is not observed early in the disease
• Also decline in striatum dopamine production
• Dopamine concentration, transporter availability and dopamine D2 receptor density all decline with age
• Serotonin receptor (5-HT2) availability in the frontal cortex also declines with age and is correlated with striatal declines of dopamine receptors
• PFC volume was negatively correlated with perseverative errors on the WISCONSIN CARD SORTING TASK (WCST) and positively correlated with a composite measure of FLUID INTELLIGENCE
• Treatment of aged rhesus monkeys with a D2 receptor agonist reduced the decline in performance on a delayed memory task
• older adults tend to exhibit less PFC activity during executive processing tasks than do younger adults
• increases in PFC activity often occur in areas contralateral to those activated in the young, a pattern — referred to as reduced hemispheric asymmetry — which indicates that such additional activations aid processing by older adults
• older adults experience greater difficulty than younger adults in performing executive processes, and that this difficulty sometimes manifests as a failure to activate PFC regions and sometimes as increased recruitment of PFC regions under relatively easy conditions.

Question 9

White matter

Answer 9

• the greatest age-related alterations in white matter are in the PFC and the anterior corpus callosum although all regions show some age-related decline in white matter integrity
• White matter abnormalities are associated with poor performance on tasks of processing speed, executive function and immediate and delayed memory, but not with declines in general intelligence measures
• decreases in processing speed and reasoning ability
• age-related changes in the grey and white matter of the frontal cortex mediate behavioural patterns of cognitive ageing in non-demented older populations.

Question 10

Hippocampus and medial temporal lobes

Answer 10

• important for declarative memory
• relatively slight age-related changes in the absence of Alzheimer’s disease
• no loss of neurons in hippocampal CA subregions and the parahippocampus with age, dendritic growth continues until after the age of 90 in humans and functional neurons continue to be generated in aged rodents
• 2–3% per decade decline in the volume of the hippocampus and the parahippocampal gyrus
• the subiculum and dentate gyrus show age-related declines in non-demented individuals
• even in healthy older adults, activity in the left hippocampus is decreased relative to younger controls during tasks that require maintenance of pictures, encoding of subsequently remembered words, and representation of conjunctions of stimulus features
• hippocampal activity in normal ageing is part of a circuit that involves the PFC.
• Reductions in hippocampal function could be reflected in modulations of PFC activation as older adults attempt to process task information by alternative routes
• Amygdala remains intact
• normal ageing has minimal structural effects on the hippocampus and adjacent MTL, although age-related functional changes might affect circuits that involve interactions between the PFC and the hippocampus, thereby causing age-related decrements in memory function that is mediated by hippocampal neurons
• pathological: crippling hippocampal involvement

Question 11

Individual variability

Answer 11

• decreases in function tend to be accompanied by increases in variability
• increased variability with age is an indication of pathological processes, whereas similar variance in younger and older samples indicates normal ageing
 BUT: several potential scenarios in which increased variability could accompany normal ageing:
 increases in strategic options through life-long learning
 plasticity in response to varied life experience
 greater variation in physical or mental activity levels (for example, before and after retirement)
• Rather than comparing variability between age cohorts, searching for regularities in individual differences within older populations is likely to inform a distinction between normal and pathological ageing processes.
• variability across individuals different life experiences, genetic influences, preferred strategies and susceptibility to neuropathology
• variability within individuals across tasks might change with age dedifferentiation hypothesis
• stability or reliability stability before the age of 60, with increased variability occurring only in later life
• individual differences in frontal-lobe integrity account for much of the variance in older adults’ performance.
• age-related declines might affect the neural correlates of processing efficiency and higher activation levels might be necessary for older adults to maintain the same level of performance as their younger counterparts
• MTL function does not distinguish high-performing from low-performing elderly subjects in source memory or strategic memory tasks, but frontal function does
• additional activations in complementary PFC regions might reflect compensatory activity, possibly due to the engagement of general-purpose mechanisms to assist in resolving difficult task demands to changes in neural plasticity with ageing or to strategic differences in the subgroup of resilient older adults
• additional areas of activation might sometimes represent non-selective recruitment of irrelevant or competing brain regions
• older individuals might show neural compensation, whereas their low-functioning counterparts, who experience failures of inhibition, show decreased activations or non-selective recruitment.
• In general, the evidence indicates that individual differences in older populations are due to variability in the severity of deficits in the two components identified
• Individual differences in normal ageing are probably due to variability in PFC integrity,and individuals might also differ in their susceptibility to the pathology of Alzheimer’s disease
• Genetic component

Question 12

Conclusion

Answer 12

• Are age-related declines due to normal or pathological processes?
• grey and white matter in the PFC and in subregions of the hippocampus lose volume in ageing non-demented humans
• Do normal age-related differences occur throughout adulthood, or only after some critical age?
• Cross-sectional studies find decline
• Volume loss in striatum throughout adulthood gradual age-related change in dopaminergic pathways
• little information about age-related changes that occur between the ages of 30 and 60
• To what extent does individual variability in behavioural, genetic and neurobiological markers of cognitive ageing reflect normal and pathological ageing?
• More attention should be paid to variability in older populations rather than merely to differences between age groups. Emphasis on determining the bases of individual differences in older populations should continue, but investigators should also seek to understand variability within individuals across tasks and across time.
• What neural mechanisms do age-related differences in anatomy and functional activations represent?
• volume losses several causes at the cellular level ,including loss of synaptic density
• changes in blood flow observed with PET and fMRI indirect measures of neural activity and could have several underlying causes
• Decreased activation with ageing due to activity in smaller neuronal populations, greater variance or less synchrony in population firing, decreased neurotransmitter binding, decreased neuronal metabolic activity or failures in afferent excitatory connections, among other possibilities
• Increased activations with ageing failures of inhibitory connections, for example.
• To what extent are strategy changes in older adults responsible for, or a response to, neural changes?
• Ageing individuals might adopt strategies in response to declines in cognitive ability or neural deficits