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      Impaired DNA repair

      Several studies have documented that brain ageing is associated with an increase in the amount of damaged nuclear and mitochondrial DNA and a concomitant reduced expression and activity of some DNA repair proteins. In aged neurons, DNA is thereby more prone to accumulating oxidative damage with important implications in terms of gene expression, synaptic plasticity, and mitochondrial function.^23,37

      Impaired neurogenesis

      Neurogenesis occurs throughout life in the ventricular‐subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. During ageing, neural stem cells and their progenitors lose their proliferative potential and become quiescent. This is thought to contribute to age‐related cognitive impairment and reduced brain plasticity.^23,38

      Dysregulated energy metabolism

      Like other organ systems, neurons may develop insulin resistance and decreased glucose transport. The consequent reduction in glucose utilization can be demonstrated by positron emission tomography imaging of radiolabelled glucose uptake and is more evident in the frontal, parietal, and temporal lobes.³⁹ The brain metabolism of lipids can also be altered with ageing, as indicated by the accumulation of ceramides and lipid‐laden cells and declining levels of omega‐3 fatty acids.²³

Changes in the neurological examination with ageing

Age‐related changes involving both the central and peripheral nervous system may result in clinical abnormalities that can be detected during a neurological examination (Table 6.2).^40,41 Typically, such neurological signs and deficits do not occur in the context of overt diseases and can be considered normal manifestations of the ageing process.⁴⁰ On one hand, they should not be overestimated, to avoid the risk of overdiagnosis and overmedicalization. On the other hand, these age‐related changes should not be overlooked, as they may contribute to functional loss and poor perceived well‐being. In this regard, even when a finding is considered within the normal limits for age, targeted interventions should be considered to optimize daily function (e.g. correction of vision and hearing loss). Moreover, it is noteworthy that some of these impairments may represent the phenotypic expressions of long prodromal phases preceding the onset of full‐blown pathological conditions. For example, olfactory dysfunction and constipation are regarded among the earliest nonmotor features of PD and can anticipate the onset of motor symptoms by years.^42,43 Finally, it should be acknowledged that the detection of neurological abnormalities might be hampered by the concomitant decline of cognitive functioning, potentially limiting the clinical assessment’s reliability.

Table 6.2 Changes in the neurological examination with ageing.

      Sources: Schott⁴⁰; Seraji‐Bzorgzad, Paulson, and Heidebrink⁴¹.

Function	Most commonly observed changes
Sensation	Impaired vibration sense in distal lower extremities Reduced pain perception Reduced joint position sense
Reflexes	Loss of ankle jerk reflexes Presence of ‘primitive’ reflexes (palmomental, snout, grasping, sustained glabellar)
Vision	Decreased near vision (presbyopia) Reduced pupillary size and reactivity Increase of saccadic latency and decrease of saccade frequency, amplitude, and velocity Breakdown of smooth eye pursuit movements with saccadic intrusions Deceased upward gaze and convergence
Hearing	Hearing loss (presbycusis), especially at higher frequencies
Smell	Diminished smell sense
Taste	Reduced taste
Gait	Decline in walking speed Decreased stride length Reduced tandem ability
Muscle	Mild increase in muscle tone Mild decrease in muscle bulk and strength
Posture	Increasingly stooped posture
Balance	Reduced ability to stand on one leg

      Vision

      Progressive impairment of visual acuity is typical of advancing age and is frequently associated with non‐neurological causes (e.g. cataract, glaucoma). Presbyopia, a decline in unaided near vision, is highly prevalent in older people and manifests as blurred vision at normal reading distances and eyestrain or headaches after reading or doing close‐up activities. With ageing, pupil size and reactivity tend to decline, and changes in saccadic movements (e.g. increased latency, decreased frequency, amplitude, peak velocity, and mean velocity) are commonly observed.⁴⁴ Tracking eye movements (or pursuits) appear less smooth with possible saccadic intrusions. The angles of vertical gaze (especially upward) are frequently symmetrically reduced in older people.⁴⁵ Convergence is also often impaired.⁴⁵

      Hearing

      Hearing loss is a common sensory impairment in older people and may have profound functional implications by interfering with communication and leading to social isolation. Accordingly, simple hearing assessments (e.g. the whisper voice test⁴⁶) should be incorporated in the neurological examination and can help determine whether the individual needs a comprehensive evaluation (i.e. audiometry, tympanometry). Typically, age‐related hearing impairment is more marked at higher frequencies and characterized by a diminished ability to understand speech in noisy environments and localize sounds.

      Taste and smell

      Disturbances in the ability to smell and taste are common in older people.⁴⁷ They can manifest as frank losses of function (i.e. hyposmia/anosmia, hypogeusia/ageusia), distortions, or hallucinations. Deficits in such chemical senses reduce the pleasure from food, represent risk factors for nutritional and immune deficiencies, and limit adherence to healthy dietary regimens.

      Sensation

      An impaired vibration sense in the big toe is observed in approximately one‐third of presumed healthy people over age 60.⁴⁸ Numbness, paraesthesia, and dysesthesia are often complained of by older people. Conversely, joint position sense, pain perception, and light touch are less frequently impaired. The decline of lower‐limb proprioception is associated with relevant balance issues and, consequently, with a higher risk of falls.⁴⁹

      Reflexes

      By the age of 80, almost one‐third of healthy people have lost their ankle jerk reflexes.⁴⁸ Knee, triceps, and biceps jerks are mostly maintained. Older individuals can exhibit ‘primitive’ reflexes, a group of behavioural motor responses that are found in normal early development and are subsequently inhibited, but that may be released from inhibition during the ageing process and/or by cerebral damage.⁵⁰ They include the palmomental reflex (i.e. ipsilateral chin movement evoked by scratching the palm along the thenar eminence), snout reflex (i.e. lips pucker in response to gentle

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