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Editors

MaijaKoivu
AnneKoivisto

Curable Causes of Cognitive Challenges and Memory Disease

Essentials

  • Identify curable causes of challenges in cognition and of memory diseases.
  • Treat these patients before their memory function or other forms of cognition are permanently impaired.

Depression

  • See Planning the Treatment of Patients with Depression.
  • Cognition problems associated with depression are usually mild: concentration and attention are impaired, intervening stimuli become more disturbing, the working memory has a reduced tolerance to loading, susceptibility to disturbances increases, and performance in memory tests becomes irregular. Depression may, however, also be associated with more severe symptoms of memory function and information processing, but these rarely reach the stage seen in dementia, where the symptom picture is extensive and eventually leads to helplessness (so-called pseudodementia).
  • In depression with severe cognitive challenges, the following features differing from memory diseases are often seen:
    • a history of psychiatric symptoms or disorders (notice that depressive symptoms in a person with no earlier history at a younger age of such symptoms may be associated with incipient memory disease)
    • the beginning of symptoms can often be defined
    • the symptoms are of short duration and they progress rapidly
    • the patient's insight into the condition and his/her emotional sensitivity are pronounced
    • there are ”I don't know” answers and selective memory gaps including both fresh and old matters
    • level of cognition varies incoherently, hints are of help and recognition is often normal, no significant problems in delayed recall.
  • Trial of therapy should be started as soon as there is a suspicion of depression or other mood disorder.

Disorders of sleep

  • Sleep disorders are a common underlying cause of cognitive challenges.
  • Lack of sleep disturbs concentration and hence the efficiency of learning. Sleep is essential for long-term memory and its disturbances impair the storing of new things into long-term memory, and they make retrieval inefficient. Decision-making is impaired.
  • Sleep disorder may be temporary or long-lasting, and organic or non-organic. Recognizing an underlying sleep disorder behind cognitive problems is important. Investigating the underlying cause is essential.
  • Sleep disorder may be caused by, for example, sleep apnoea with often associated obesity, restless legs syndrome, hypersomnia, delayed sleep phase syndrome, narcolepsy, chronic pain and pain medication, drugs of abuse (including alcohol), many neurological, psychiatric or other somatic illnesses (e.g. MS, brain tumours, depression, infections, chronic inflammatory diseases, such as rheumatoid arthritis, coronary artery disease, diabetes), stress, menopause and medication.
  • The treament and treatment plan depend on the underlying cause; pharmacotherapy is used according to an individual plan, as necessary.
  • Non-pharmacological treatment of sleep disorder includes
    • regular sleep rhythm
    • regular physical exercise, but not close to bedtime (3 hours before)
    • avoiding caffeine, alcohol and nicotine in the evening before bedtime
    • relaxing activities in the evening, such as bathing, sauna, reading, avoidance of activating tasks
    • finishing dinner a couple of hours before bedtime
    • peaceful, dimmed room, cool sleeping enviroment and, as necessary, relaxing music
    • avoiding use of TV, computer or mobile phone in bed prior to going to sleep.

Hypothyroidism

  • Memory symptoms may in the elderly disguise other symptoms of hypothyroidism Hypothyroidism.
  • Slowness of cognitive processing, difficulties in learning new things and impairment of executive functioning may occur.
  • Neuropsychiatric symptoms in the form of depression, paranoia and psychosis may occur.

Hyper- and hypocalcaemia

  • Serum calcium concentration may be only slightly increased even if the patient has a severe impairment of memory function and information processing. Ionised calcium is a better marker of the body's calcium balance.
  • The prevalence of hyperparathyroidism Hypercalcaemia and Hyperparathyroidism in the elderly is about 3%.
  • In addition to memory problems, hyperparathyroidism may be associated with apathy, concentration difficulties and irritability.
  • Some patients will benefit from surgery, and osteoporosis associated with the disease will be concomitantly treated.
  • Manifestations of hypoparathyroidism include, in addition to impaired memory function and information processing, also epileptic seizures, ataxia, and muscle spasms.

Vitamin B12 deficiency

  • Symptoms of impaired memory function and information processing have been found in 25% of patients.
  • Vitamin B12 deficiency causes difficulties in visuospatial perception and abstract thinking. Additionally, mood changes (agitation, mania, depression) as well as psychotic symptoms may occur alongside memory problems.
  • Symptoms may precede changes in blood tests or appear without any changes in blood tests.
  • Diagnosis: determination of vitamin B12 as holotranscobalamin
    • Concentration < 20 pmol/l suggests B12 deficiency.
    • Concentration 20-50(-70) pmol/l: possible B12 deficiency
    • As further investigation, determination of plasma homocysteine or of the more specific methylmalonate, or a therapeutic trial with vitamin B12 (intramuscular or oral). The impact of the trial must be documented.
  • Treatment initially with vitamin B12 injections daily and maintenance therapy at 1-3-month intervals
  • Oral administration with dose 1 mg/day may also be applied (1% is absorbed through passive diffusion independent of intrinsic factor). Even then the initial treatment is recommended to be given as injections.

Vitamin B1 (thiamine) deficiency

  • Thiamine deficiency can cause Wernicke's syndrome, which includes at least 2 of the following:
    • ocular findings (e.g. nystagmus or gaze paresis)
    • cerebellar findings (e.g. ataxia or dysdiadochokinesia)
    • mental symptoms (decreased level of consciousness or mild to moderate anterograde and retrograde memory disturbance)
    • imbalanced diet according to patient history, nausea and vomiting in pregnancy, sequela of bariatric surgery, severe gastroenteritis or alcoholism.
  • Dosage of thiamine
    • In a confusional state and in alcohol withdrawal 100-250 mg i.v. once daily before starting sugar-/carbohydrate-rich diet
    • In diagnosed or suspected Wernicke's syndrome 200 mg i.v. every 8 hours until the patient's condition is settled or restored Neurological Disorders and Alcohol.

Niacin (nicotinic acid, vitamin B3) deficiency

  • Deficiency leads to pellagra (dementia, dermatitis and diarrhoea).
  • Initially symptoms of the central nervous system: fatigue, anxiety and irritability
  • Later on, psychotic symptoms and cognitive impairment develop, and, additionally, rigidity and decreased level of consciousness may occur.
  • Cognitive symptoms resemble those of thiamine deficiency.
  • Treatment: niacin 150 mg once daily, in severe cases 1 g × 3-4 parenterally

Folate deficiency

  • The role of the deficiency in the development of memory symptoms is unclear.
  • Symptoms resemble the symptom picture caused by vitamin B12 deficiency
  • It is recommended to correct the potential deficiency by replacement therapy.
    • Folic acid 1 mg initially 3 times daily and later on once daily for a period of at least 6 months.

Chronic subdural haematoma

  • The majority of these patients are elderly.
  • In one-half of them symptoms include memory and other cognitive symptoms and confusion that progress within a short time frame.
  • The trauma may have occurred several months earlier. Some of the patients may not be aware of any head injury.
  • Bilateral subdural haematoma in particular does not necessarily include unilateral neurological symptoms, nor is it always visible in the CT scan.
  • Treatment consists of neurosurgical removal of the haematoma; however, if the haematoma is less than 1 cm in thickness, monitoring of resorption is frequently sufficient.

Normal-pressure hydrocephalus (NPH)

  • Partial disruption in the circulation of the cerebrospinal fluid. The condition may develop as a delayed complication of meningitis, encephalitis, subarachnoidal haemorrhage, brain injuries, and brain surgery. In some cases the cause is not known and the condition is called idiopathic normal-pressure hydrocephalus (INPH).
  • NPH symptoms are progressive.
  • Cognitive symptoms typically manifest as psychomotor slowness. Speech fluency and application of learned things are impaired, and memory lapses occur.
  • Balance and gait are impaired. Getting started with walking and turning while walking become more difficult and gait apraxia occurs - walking is wide-based, i.e. legs are separated, and steps are short. There may also be increased muscle tone i.e. rigidity.
  • In some persons, urinary continence is weakened (often in later stages of the disease).
  • Surgical shunting can relieve the cognitive symptoms in some patients, particularly if the symptoms have not lasted for long. It is advisable to also take a brain biopsy during the shunt operation to examine for the possibility of concurrent Alzheimer's disease (AD). A large share of patients have a concurrent AD or vascular memory disorder.
  • Improvement of cognitive symptoms may take place over a period of several months. In some patients, however, no longer term treatment response can be achieved concerning cognition (considering the aforementioned comorbidities), even though treatment response concerning motor function can be observed.

Infections

  • Even today, cases of memory disease caused by tertiary syphilis are found Syphilis.
  • Impairment of memory function and information processing may also be associated with
    • sequelae of suppurative or tuberculous meningitis
    • immunodeficiency.
  • The Borrelia burgdorferi spirochete may cause chronic encephalitis and impairment of memory function and information processing (see EncephalitisLyme Borreliosis (LB)).

Uraemia

Liver diseases

  • The accumulation of toxic substances in the brain is a generally recognized cause of hepatic encephalopathy Cirrhosis of the Liver.
  • The blood ammonia concentration is increased.
  • Symptoms include concentration difficulty, impaired cognition, apathy, difficulties in performing motor functions, and flapping tremor. In the more difficult form of the disease, there may be reduced consciousness, confusion, behavioural changes and finally coma.

Chronic pulmonary diseases

  • These may cause cerebral insufficiency related to oxygen deprivation and carbon dioxide retention; however, only an extremely severe pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) may cause actual extensive impairment of memory and information processing which would hamper the everyday life.

Hypoglycaemia

Tumours

  • Symptoms related to malignant tumours (e.g. gliomas and metastases) usually progress rapidly; thus the patient should be examined with appropriate urgency.
  • Symptoms related to benign tumours may progress insidiously, which can cause difficulties in their differentiation from Alzheimer's disease, psychiatric conditions, or other disorders. In such cases, the tumour often resides in the frontal lobe or falx.
  • With malignant tumours, a memory disease may also be expressed as a paraneoplastic phenomenon. This is most often associated with lung or breast cancer.

Medications and abuse of drugs

  • The pharmacokinetics and pharmacodynamics of pharmaceuticals change with age, which predisposes to cognitive adverse effects.
  • Anticholinergic drugs
    • Inhibit the functions of acetylcholine receptors (the cholinergic network is important for the state of mental alertness, attentiveness and memory).
    • In addition to memory problems, confusion and agitation may occur.
    • Particularly persons with organic brain disease are susceptible to adverse effects.
    • Anticholinergic drugs include: tricyclic antidepressants, conventional antipsychotics, scopolamine, in particular first-generation antihistamines, and most drugs used for urinary leakage.
  • Alcohol
    • Intoxication and hangover reduce alertness and ability to concentrate.
    • Alcohol causes cognitive problems.
    • Thiamine deficiency is a potential additional cause.
    • Long-term impacts of alcohol
      • Executive functioning is reduced more than memory functions or linquistic skills.
      • Reduced problem-solving capacity and ability for abstract thinking
      • Imaging studies reveal atrophy in the cerebellum and frontal lobe.
    • Alcohol abstinence for at least 3 months before memory investigations
  • Drugs of abuse
    • Most drugs negatively affect the working memory and episodic memory.
      • Cannabis: cognitive flexibility and learning ability are reduced, ability to stay alert is impaired
      • Amphetamine: cognitive function is slowed down, delayed recall and verbal fluency become worse
      • Opioids: recall becomes worse, cognitive flexibility is impaired

Others

References