Forgotten

Behavioral Health


Diagnosis and reasoning

Cognitive decline is commonly encountered in the primary care setting; unfortunately, it is a non-specific symptom, being caused by a broad range of disorders. A detailed history is key to the evaluation of these patients, as this can rapidly rule out many of the potential differentials.


Considering the lady in this case, note the insidious and progress memory loss that is now affecting her ability to look after herself. This is most suggestive of dementia; her clinical history and the 20/30 mini mental state examination (MMSE) score support this possibility. However, it is still important to consider and exclude several potential mimics.


First of all, organic conditions such as thyroid disorders and vitamin B12 or folate deficiency can present in this manner. However, in this patient, a thyroid profile and serum B12/folate levels are both within normal parameters, excluding the above possibilities.


Second, mild cognitive impairment (MCI) can also present with memory loss. However,

by definition MCI does not result in impairment of the ability to perform activities of daily living. This is not the case with this patient.


Depression can both mimic dementia, and co-exist along with it. However, she has insufficient symptoms to meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for depression; in addition, her geriatric depression scale (GDS) score is also within normal limits.


Given the exclusion of these differentials, dementia remains the likely cause of her symptoms; the next step should be determination of the likely underlying etiology. As Alzheimer's disease is the commonest cause of dementia, it is logical to consider this diagnosis first – and in fact, she does meet the DSM-5 criteria for diagnosis of the condition. However, the other key forms of dementia should still be excluded, as their treatment is markedly different.


The presence of hypertension and dyslipidemia indicates that vascular dementia should be considered. However, such patients usually experience a sudden onset of symptoms, with stepwise progression; focal neurological signs may also be present.


Dementia with lewy bodies (DLB) is another possibility; however, visual hallucinations and fluctuating cognition are prominent, as are sleep disturbances. There may also be features of parkinsonism on examination.


Parkinson's disease may also result in a progressive dementia; however, this is a late feature of the condition, with motor symptoms usually appearing long before. Thus, in summary, Alzheimer's disease is indeed the likely diagnosis.


An important question is whether imaging of the brain should be performed; while the routine use of neuroimaging in the workup of dementia is controversial, the presence of vascular risk factors in this patient suggests that magnetic resonance imaging (MRI) might indeed be justifiable.


However, the MRI only reveals medial temporal and hippocampal atrophy, which is a characteristic imaging feature encountered in the early stages of Alzheimer's Disease. Note that neuropsychological assessment is not required here, given the classical presentation.


Donepezil is the first-line agent in patients with moderate dementia; it is known to improve both the quality of life and cognitive functions. While memantine is also used in the treatment of Alzheimer's Disease, it is typically reserved for individuals with severe dementia (i.e. an MMSE score < 10).


Aspirin would have been indicated if vascular dementia were present; and ropinirole is used in the management of individuals with Parkinson's disease.

Discussion

Alzheimer's disease is a progressive neurodegenerative condition; it is the most common cause of dementia worldwide, with over 35 million individuals affected. The underlying pathophysiology appears be deposition of β-amyloid plaques, neuronal inflammation in the neocortical terminal fields, and development of neurofibrillary tangles in medial temporal-lobe structures; deficiencies in cholinergic transmission have also been identified. The cerebral cortex becomes progressively atrophic as the disease progresses.


Known risk factors for the condition include increasing age, a family history of the disease, Down syndrome, obesity, dyslipidemia, hypertension, insulin resistance, and certain genetic variants.


Affected individuals commonly present with deterioration of memory, the inability to perform activities of daily living (ADL), and behavioral disturbances.


Slowly progressive confusion and disorientation with respect to time and place, loss of judgment, and impairment of executive functions are important and easily identifiable components of Alzheimer's disease. Associated features such as nominal aphasia, apraxia and agnosia may also be identified. Rapid fluctuations of mood may become apparent as the disease progresses, with the patient suddenly becoming anxious or tearful. Depression and anxiety can occur in parallel. Hallucinations and delusions are uncommon and tend to occur in later stages of the disease.


Individuals who progress to severe dementia usually become completely dependent on their caregivers, and may show significant weight loss, difficulty in swallowing, and loss of bladder and bowel control.


The Diagnostic and Statistical Manual of mental disorders, 5th edition (DSM-5), has specific diagnostic criteria for Alzheimer's Disease; these include:

  • Evidence of cognitive decline from a previous level in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition), based on the concern of the patient, a knowledgeable informant or a clinician, or standardized neuropsychological testing.
  • Cognitive deficits interfering with independence in everyday activities.
  • The cognitive deficits do not occur exclusively in the context of delirium
  • The cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia).
  • An insidious onset and gradual progression of impairment in one or more of the above mentioned cognitive domains

Apart from the above, separate sets of criteria are defined for categorization of 'possible' or 'probable' Alzheimer's disease.


Alternate conditions that can mimic dementia should be excluded. These include hearing and visual defects, mild cognitive impairment, organic conditions such as hypo– or hyperthyroidism, vitamin B12 or folate deficiency and depression. Structural imaging of the central nervous system should be performed with CT or MRI brain. Syphilis serology, lumbar puncture, electroencephalography (EEG), and genetic testing are only indicated if there is suspicion of an alternate illness.


Alzheimer's Disease is currently incurable. The management is aimed at slowing progression and alleviating symptoms. Cholinesterase inhibitors such as donepezil, galantamine and rivastigmine are useful in the management of mild to moderate dementia; they both alleviate symptoms and improve cognitive function.The N-methyl-D-aspartate (NMDA) antagonist memantine is of use in patients with severe dementia, either alone, or in combination with cholinesterase inhibitors.

Non-pharmacological measures are mainly of use in managing coexisting behavioral disturbances such as agitation, psychosis and depression; these include behavioral therapy, cognitive stimulation, environmental modification, multisensory stimulation therapies involving aromas, light and music, and caregiver training programs. Structured exercises and conversation should be incorporated into daily activities in order to preserve the patient's mobility and speech.

In general, Alzheimer's Disease progresses from mild cognitive impairment to complete dependency and death over a period averaging 10 years.

Take home messages

1. Alzheimer's disease is the commonest cause of dementia worldwide.

2. A range of organic and psychiatric causes can mimic Alzheimer's disease, and should be excluded prior to arriving at this diagnosis.

3. While is Alzheimer's disease is incurable, early diagnosis and treatment has a significant impact on disease progression.

References

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