Cognitive impairment in Parkinson’s disease

The prevalence of Parkinson’s disease increases with advancing age. It is a disease in which the non-motor manifestations impact the patient’s quality of life and that of their carer more than the motor symptoms.^1,2

This is especially important for older people, as they often live with another older person who becomes their carer. Therefore, it affects healthcare providers and those developing policy for an ageing population.

Introduction

Parkinson’s disease will be diagnosed in around one in every 35-40 people during their lifetime, with the prevalence being at its highest in the over 75s. It is second to Alzheimer’s disease as the most common neurodegenerative condition but with very different symptoms. In Parkinson’s disease these are separated as motor and non-motor symptoms.

The greatest burden on patients and carers comes from the non-motor symptoms,³ many of which are poorly or not at all responsive to dopaminergic therapy. Dopaminergic therapy being usually either a dopamine precursor (Levodopa), a dopamine breakdown inhibitor (e.g. rasagiline, entacapone or opicapone), or a dopamine agonist (e.g. ropinirole, pramipexole, rotigotine and apomorphine).

The table below lists some of the more significant non-motor symptoms and associated problems in older patients and suggested management examples.

 

Symptom	Problem	Example of management
Constipation	Slows L DOPA absorption	Assess bowel frequency and direct patient to use laxatives and review by usual care team.
Sleep disturbance, including Rapid Eye Movement Sleep Behaviour Disorder (REMSBD)	Falls, carer distress	Sleep hygiene, medication management with clonazepam or melatonin by specialist
Nocturia	Falls	Assessment by specialist, PSA check in male patients, Antispasmodic agent (preferably non-anticholinergic)
Impotence, impaired sexual arousal	Impact on intimate relationships	Specialist assessment, Phosphodiesterase inhibitors (but risk of syncope), advice from Patient groups (Parkinson’s UK etc)
Cognitive impairment (Mild Cognitive Impairment [MCI], Dementia)	Increased dependence	Specialist assessment and consideration of acetylcholinesterase inhibitor
Hypersalivation (drooling)	Dysphagia, intermittent coughing, impairment particularly of volume of speech	Specialist assessment and consideration of locally acting anticholinergic. SALT (Speech and Language Therapist review)

 

Although I have previously reviewed some of the impacts on end-of-life care from these symptoms,⁴ in this article, the focus is on cognitive impairment and Parkinson’s disease and the long-term impact on carers. Some of these are seen in conditions other than Parkinson’s disease, but they do form part of the clinical picture in older persons with Parkinson’s disease.

What are the different trajectories seen in Parkinson’s disease?

While there is evidence of differing phenotypes representing a slower progression of motor and non-motor symptoms compared with a faster progression,⁵ it is important to note that in older patients who first present with motor symptoms (e.g. tremor, falls, or slowness of gait) there is also a higher likelihood of the existence of other pathology associated with cognitive impairment.

It is often the pattern of impairment in cognitive domains that may impact on carer burden.⁶ This might be identified and discussed at consultation and then focused carer support targeted to those patients.

Identifying the appearance of non-motor symptoms in older patients, such as sleep disturbance and the presence of REM Sleep Behaviour Disorder, cognitive impairment and falls, suggests progression of the disease beyond what can only be managed with dopaminergic therapy and the need for supportive care. Carer stress and episodes of crisis are often related to these symptoms and are also associated with the presence of apathy and depression, which can exist prior to motor symptoms early in the disease across all age groups.

However, in older patients, there should also be consideration of cognitive impairment developing and using simple tests by the usual care team, such as the Pill Questionnaire test⁷ and Single Question Screening for Cognitive Impairment,⁸, as well as the disclosure of a problem with “memory” or “thinking” by the patient or the carer. Although these are not useful alone, taken together and in the clinical context they are helpful in deciding who to consider for further testing or to refer.

What changes in cognition can be expected with normal ageing?

Cognitive function depends on sensory information arriving at the brain and its integration into different parts of the brain associated with, for example, visuospatial, language, and memory tasks. Memory can be divided into short-term or long-term, with the long-term divided into conscious recall (declarative, e.g., episodic) or non-conscious recall (non-declarative, e.g., a learned motor skill). These are then modulated by arousal systems from the brainstem or cortex, which determine attention to a task.

The latter, namely cortical modulation by the prefrontal cortex, is implicated in emotional functioning.⁹

Testing of cognitive function broadly differentiates between the function of these different brain areas, such as sustained attention, short-term (or working) memory, verbal fluency, and visuospatial abilities.

Furthermore, a ratio of the Verbal Fluency and Language over Orientation and Memory (VLOM) tests in the ACE3 (Addenbrookes Cognitive Examination III, a commonly used cognitive screen) can suggest differentiation between the Alzheimer’s type from the Frontotemporal type cognitive impairment patterns.¹⁰

Dementia seen in older adults with Parkson’s disease often has features of impaired frontal lobe function^11, as is also seen in Frontotemporal Dementia. This is in contrast to Alzheimer’s type dementia, where predominantly episodic memory, perception and language domains are affected, but emotional functioning can be preserved.

Age-related cognitive decline in healthy older adults is seen across cognitive domains,¹² but emotional functioning can be preserved in healthy older adults (at least in recognising emotions between couples) and in some neurodegenerative conditions that do not predominantly affect the frontal lobes, such as Alzheimer’s type dementia.^13,14 This has been suggested to be a reason for the preservation of marital relationships and the better health of carers of these patients.^15,16

What are some of the pathologies associated with cognitive impairment seen in older persons?

The diagnosis of dementia type is based on certain disease-specific criteria, as suggested by NICE, with perhaps most importantly consideration given to other clinical conditions, including depression, delirium and the prescribing of anticholinergic medication leading to anticholinergic burden.

Although there is often a focus on distinct clinical and pathological entities of cognitive impairment, it is a mixed neuropathology that is found most commonly in community-based studies. This was demonstrated in a UK population-based longitudinal study of the ageing population. which included an epidemiological assessment of neuropathology.¹⁷

When selection is based on age, then a mixed neuropathological picture emerges with a predominance of vascular and Alzheimer’s type pathology. A model based on the presence of different neuropathologies contributing to Alzheimer’s disease neuropathological change (ADNC) predicted the presence of clinically evident dementia (75% cases), “but no individual feature was sufficient in relation to an individual”. There was also a “high frequency of dementia-neuropathologies irrespective of whether dementia was present”.¹⁷

This tells us that in most older people there is evidence of neuropathology usually associated with differing types of dementia but that “other factors are important in determining which individuals will show cognitive deterioration” such as neuroinflammation and cell-ageing mechanisms.¹⁷

Diagnosing dementia

In the NICE Clinical Knowledge Summary (CKS), dementia features under the following headings with useful explanations. NICE guidance also stresses the “importance of relationships and interactions with others to the person with dementia” and also taking a history from “someone who knows the person well”.¹⁸

 

Cognitive impairment	Memory loss — the person may defer to family when answering questions, have difficulty learning new information or remembering recent events or people’s names, be vague with dates, and/or miss appointments. Problems with reasoning and communication. Difficulty in making decisions. Dysphasia. Difficulty in carrying out coordinated movements, such as dressing. Disorientation and unawareness of the time and place. Impairment of executive function, such as difficulties with planning, judgement, loss of initiative, and problem-solving.
Behavioural and psychological symptoms of dementia (BPSD). These tend to fluctuate, may last for 6 months or more	Psychosis — the person may have delusions (which may be persecutory) and/or hallucinations (visual and auditory). Agitation and emotional lability — the person may be easily upset, argumentative, shout, have mood swings, and/or exhibit physically and verbally challenging behaviour. Depression and anxiety — the onset of depression in later life is a warning sign of dementia. Withdrawal or apathy. Disinhibition — the person may display socially or sexually inappropriate behaviour. Motor disturbance — wandering, restlessness, pacing, and repetitive activity may be reported. Sleep cycle disturbance or insomnia. Tendency to repeat phrases or questions
Difficulties with activities of daily living (ADLs)	In the early stages of dementia this may lead to difficulty carrying out complex household tasks. In the later stages, basic ADLs such as bathing, toileting, eating, and walking become affected.
Symptoms related to specific subtypes of dementia	For Alzheimer’s disease: The presenting symptom is usually loss of recent memory first, and often difficulty with executive function and/or nominal dysphasia. There is also loss of episodic memory — this may include memory loss for recent events, repeated questioning, and difficulty learning new information. Cognitive deficits may include aphasia, apraxia, and agnosia. For vascular dementia: Stepwise increases in the severity of symptoms — subcortical ischaemic vascular dementia may present insidiously with gait and attention problems and changes in personality. Focal neurological signs (such as hemiparesis or visual field defects) may be present. For dementia with Lewy bodies: Core clinical features are fluctuating cognition; recurrent visual hallucinations; REM sleep behaviour disorder and one or more symptoms of parkinsonism disorder; bradykinesia, rest tremor, or rigidity. Memory impairment may not be apparent in early stages. For frontotemporal dementia: Personality change and behavioural disturbance (such as apathy or social/sexual disinhibition) may develop insidiously. Other cognitive functions (such as memory and perception) may be relatively preserved.

 

In the case of Parkinson’s disease, dementia is the presence of a dementia syndrome within the context of PD.¹⁹ The common presence of mixed neuropathology in the older population suggests that in the older PD population, the presence of dementia or mild cognitive impairment must be considered early together with its impact on carers. This is because some of the features commonly associated with MCI or dementia in Parkinson’s disease, such as apathy, depression, sleep disturbance and visual hallucinations, can have a significant impact on carers.

How can dementia, particularly that associated with PD, affect the relationship between the patient and their partner?

In the UK Office for National Statistics data from 2018, around half (46%) of those households composed of a person 70 years or over had at least one other person also over 70. There has also been an increase in the proportion of the population over 70 being married.²⁰ Overall, this suggests that many older adults who have neurodegenerative conditions have an older carer living with them. It follows that the burden of caregiving in this population is, therefore, substantial with the consequent morbidity associated with it.

Dependence and carer burden are significantly associated with the progression of dementia, as indeed, they are in other chronic diseases. The relationship between the carer and the patient during the course of a chronic disease which affects them both can be called a “dyad”. The dyad in the context of older adults is different when considering dementia in contrast to a patient with a hip fracture or heart attack where the care needs might be seen to end with recovery.^21,22

When considering older patients and their elderly caregivers, often a spouse, there exists an interdependence that is part and parcel of that couple’s relationship. This interdependence may be temporary when recovery is predicted to occur but permanent in a progressive disease such as dementia or when a frail state is reached from co-morbidity or deconditioning.

In work by Prof Robert Levenson at the University of California, Berkeley, looking at different types of dementia and the emotional responsiveness of the patients, there was a preserved response in Alzheimer’s type compared with a loss of response in fronto-temporal type. This was seen to affect married relationships in that the caregiver often became depressed.²³ It might be extrapolated to PD dementia that part of the carer burden of older carers stems from this loss of emotional responsiveness in frontal type dementia, although this needs to be further studied. However, it might be justifiably supposed that in PD Dementia, targeted strategies to help the caregiver could help mitigate some of this burden.

What strategies can we use to help carers?

When faced with a patient and their long-term carer in the clinical setting or in their home, there should be an appreciation not only of the symptoms and signs relevant to the patient’s illness but also the impact of these on the carer and also an appreciation of the positive and negative impacts and burdens on the relationship between the two and facing the healthcare professional.

It is not within the scope of this article to discuss strategies for dealing with carer stress or burden, but this article seeks to explain some of the underlying reasons leading to relationship stress in the context of older sufferers of Parkinson’s disease and tentatively asks the reader to explore some of these strategies and perhaps implement some to help maintain often long-term relationships.

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Dr Robin Davie is a Consultant Physician in Geriatric Medicine at Wrexham Maelor Hospital in North Wales, UK

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References

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