20th July 2023

Dementia and Depression

Dementia

Dementia is a term used to describe a number of neurodegenerative conditions which are characterised by progressive loss of cognitive function.

Diagnosis

The general approach to diagnosis should incorporate a detailed history, including collateral history if available, using a valid structured cognitive assessment tool and undertaking investigations to exclude reversible causes of cognitive decline. This would include blood tests and structural imaging. The person should be referred to a specialist dementia diagnostic service.

The main causes of dementia are the subtypes of Alzheimer’s disease, vascular dementia, dementia with Lewy bodies and frontotemporal dementia. In addition to this, there are some rarer causes, such as Huntington’s disease and prion disease, and there are some reversible causes of dementia, for example, normal pressure hydrocephalus.

Differential diagnoses to consider include delirium, depression, mild cognitive impairment, vitamin deficiency, metabolic disorders such as hypothyroidism and Addison’s disease, infections, including HIV and syphilis, and adverse drug effects.

Management

Management should take a holistic approach. People diagnosed with dementia should be given information about their condition and what support is available to them. There should be a thorough assessment of their home environment, as well as their self-care needs. Advance care planning should be offered at an early opportunity and regularly reviewed.

Pharmacological agents are available for some, but not all types of dementia. The aim of these treatments is to slow the progression of symptoms and reduce behavioural symptoms.

Ethics

It is important to act within the legal and ethical frameworks when supporting and treating a person living with dementia. One of the most relevant laws is the Mental Capacity Act 2005. The GMC also provides guidance relating to mental capacity.

Mental capacity is decision specific, and all steps should be taken to maximise a person’s capacity. In cases where a person does not have capacity, then the team should explore if there is a lasting power of attorney for health and welfare. Other principles include exploring any previous stated wishes or advance care plans, involving the next of kin and taking the least restrictive option.

Types of dementia

Alzheimer’s Disease (AD)

AD is the most common form of dementia. It can also co-exist with other forms of dementia.

The underlying changes seen in AD include cerebral atrophy, deposition of A-beta amyloid peptides, neurofibrillary tangles comprising tau protein and reduction in acetylcholine production.

Various risk factors have been associated with an increased risk of developing AD. These include smoking, obesity, a diet with excess saturated fats and excess alcohol intake.

Features include memory loss, deterioration of executive function, for example, difficulty in planning, progressive difficulty in conducting activities of daily living and behavioural and psychological symptoms.

In addition to the general approach to diagnosis, assessment for AD should test verbal episodic memory. Further tests that can be used in the diagnosis of AD include either FDG-PET, perfusion SPECT or examination of cerebrospinal fluid for tau and amyloid proteins.

Pharmacological management of AD:

• Mild to moderate – acetylcholinesterase inhibitor monotherapy e.g., donepezil, galantamine or rivastigmine.
• Severe or moderate AD where acetylcholine inhibitors aren’t tolerated or are contraindicated – memantine monotherapy.
• Memantine can be used in addition to those with established AD who are already taking an acetylcholinesterase inhibitor if they have moderate to severe disease.

Alongside these treatments, it is also worth reviewing the person’s current medications and considering minimising the use of medications with an increased anticholinergic burden.

Vascular dementia

Vascular dementia is the second most common form of dementia.

It is caused by a loss of brain parenchyma secondary to cerebrovascular causes such as small vessel disease, infarction, and haemorrhage. The risk factors are the same as those for other cardiovascular diseases e.g., increasing age, obesity, smoking and hypertension.

Vascular dementia classically progresses in a stepwise fashion.

Symptoms relating to loss of executive function tend to be more prominent than memory loss.

Neuroimaging e.g., MRI or CT brain, can be used to identify infarcts and assess the burden of small vessel disease, which can support a diagnosis of vascular dementia.

Other investigations to consider include an ECG, carotid ultrasound, and echocardiography.

Pharmacological management with acetylcholinesterase inhibitors or memantine should only be used if there is co-existent Alzheimer’s disease, dementia with Lewy bodies or Parkinson’s disease with dementia.

Dementia with Lewy Bodies (DLB)

DLB is the third most common cause of dementia.

The pathophysiology is characterised by the accumulation of alpha-synuclein and ubiquitin, which form Lewy bodies. There are also decreased levels of acetylcholine. DLB affects the substantia nigra, limbic regions and neocortex.

The core clinical features are fluctuating cognition, visual hallucinations, REM sleep disorder and features of parkinsonism.

Acetylcholinesterase inhibitors can also be used in the treatment of dementia with Lewy bodies.

Frontotemporal dementia (FTD)

FTD is characterised by neurodegeneration affecting primarily the frontal and temporal lobes. There are various subtypes, but the disease typically manifests as changes in personality, behaviour, and social conduct or as a language disorder.

It tends to present in a younger cohort, with the average age of onset between 45-65 years of age. Around one-third of patients are thought to have a strong family history. There is also an association between Parkinson’s disease and motor neurone disease.

Diagnosis can be challenging as the symptoms can often mimic those of psychiatric disorders. A full collateral history is key, particularly from someone who knew the person before the onset of the disease.

Cognitive assessment may be normal in the earlier stages of the disease. There are some screening tools that are more directed towards frontal lobe function; these include the frontal assessment battery and the executive interview. A full set of investigations to exclude alternative causes should be carried out.

Further formal assessment requires referral to a specialist. Imaging used in diagnosing FTD are FDG-PET or perfusion-SPECT.

Currently there is no treatment for FTD, and therefore management is supportive.

Creutzfeldt-Jakob disease (CJD)

CJD is a form of prion disease that can present as rapidly progressive dementia.

CJD can be sporadic, genetic, or acquired. Accumulation of prions in the central nervous system leads to cell injury and death. It is characterised by a spongiform appearance on microscopy.

In the history, it is important to explore any potential risk factors, e.g., medical procedures, including transfusion of blood products, family history, travel history and beef consumption.

Sporadic CJD typically occurs in the seventh decade of life, whereas variant CJD, a form of acquired CJD, commonly affects younger adults.

Key investigations include MRI and real-time quaking-induced conversion testing on cerebrospinal fluid. Genetic screening can also be performed.

There is no disease-targeted treatment available, and therefore management is supportive.

Depression

Background

Depression is common in the older population, affecting 22% of men and 28% of women over the age of 65. It affects those for whom depression was diagnosed earlier in life and those who develop depression in their later years.

Risk factors include chronic illness, female sex, older age, psychosocial issues, and a personal history of depression.

Assessment and Diagnosis

Diagnosis in older adults may be more challenging, and it is thought that depression is underdiagnosed in this population. In addition, depression is associated with increased morbidity.

Depression presents with a variety of symptoms which can be psychological, physical, and social. Psychological symptoms include low mood, diminished interest or pleasure in activities, loss of energy or motivation and feelings of worthlessness. Physical symptoms include weight loss, significant changes in appetite and sleep disturbance. Social symptoms include withdrawing from friends and family and difficulties at home or work. In severe depression, there may also be features of psychosis.

The current NICE guidance refers to both DSM-IV and ICD-10 classification systems which are used to aid formal diagnosis, with its preferred system as DSM-IV. These systems have now been upgraded to DSM-V and ICD-11, respectively, though the NICE guideline has not yet been updated to reflect this.

Shared criteria of both systems are that they require one symptom to be either low mood or anhedonia, symptoms should be present for most of the day for at least two weeks and symptoms have a significant impact on function. They differ in the threshold number of symptoms and the ICD-11 includes hopelessness as a characteristic symptom, whereas it does not feature in the DSM-V. It is also worth noting that the updated DSM-V has removed bereavement as an exclusion and instead recommends clinical judgement, however the ICD-11 still includes it, with a certain threshold that must be met to diagnose a depressive episode superimposed on normal grief.

The classification criteria help determine the severity of depression (mild, moderate, and severe), based on the number of symptoms, along with the degree of functional impairment.

These diagnostic criteria are the same for older adults, as they are for younger patients. However, there are other tools that can help recognise and diagnose depression in older people. These include the Geriatric Depression Scale, Cornell Scale for Depression in Dementia, Patient Health Questionnaire-9.

The British Geriatric Society (BGS) gives guidance on Comprehensive Geriatric Assessment which includes reviewing the person’s mood and mental health. The BGS highlight the importance of exploring if the patient has any suicidal thoughts, as older adults with depression are at higher risk of completed (fatal) suicide than younger adults.

Management

The management of depression in older patients is similar to that recommended for adults, however there are some additional considerations. NICE provides a separate guideline for those with a chronic physical health problem, which is likely to be relevant to the older population.

All patients should be asked about suicidal ideation and intent in order to assess risk and ensure appropriate support and treatment is put in place.

Management should be guided by the clinical needs, patient preference and treatment history. Treatment options range from guided self-help, group-based therapies to individual counselling and pharmacological management.

When considering pharmacological treatment options, it is important to consider the patient’s medical history, current medications, and any previous experience of antidepressants. The patient should also be informed about potential adverse events associated with pharmacological treatment e.g., discontinuation symptoms and relevant side effects.

Generally, selective serotonin reuptake inhibitors (SSRI) are used first line, such as citalopram. In all patients, but particularly older adults, it is important to consider the increased risk of bleeding associated with SSRIs. Medications should also be prescribed at age-appropriate doses.

It is also crucial to assess suicide risk, as those at high risk will need closer monitoring when starting treatment.

Response to treatment should be reviewed in the first 2-4 weeks, however the person should be assessed sooner if there is a particular risk of suicide or pharmacological treatment has been started for a person aged 18-25 years.

To prevent relapse, antidepressants should be continued for at least 6 months after remission of symptoms.

For severe depression or refractory depression, electroconvulsive therapy can be considered.