Identify memory loss disorders

Red-flag signs can help identify pathological causes of forgetfulness, says Dr Andrew Larner.

Forgetfulness is part of the human condition. Who has not, on occasion, forgotten the name of a recently introduced acquaintance, or gone into a room for something and forgotten what?

How, then, can clinicians reliably differentiate normal, physiological, forgetfulness from pathological states accompanied by memory impairment, such as Alzheimer's disease?

With difficulty, is the short answer, especially in the earliest stages of disease, which most often occur at the same time of life that normal physiological cognitive inefficiency becomes apparent.

In this context, GPs are optimally placed since primary care facilitates longitudinal patient assessment. This may be supplemented by additional history, which should be actively sought.

Red flags
Clues or red flags may be used to identify more serious causes of forgetfulness. As previously suggested by Richard Asher in the context of medical writing, applying Kipling's 'six honest serving men' - what, why, when, where, how and who - may help in diagnosis (see panel, right).

Causes of memory loss
Many primary neurological or psychiatric diseases, and some general medical disorders with secondary neurological complications, for example diabetes, respiratory failure or liver failure, may cause memory impairment or even frank dementia (see table).

In clinical practice, however, the two most common are Alzheimer's disease and depression, and these merit consideration in every patient with memory complaint. These are not mutually exclusive.

Alzheimer's disease typically presents with failure to recall recent day-to-day events or activities (episodic or autobiographical amnesia) but often with well-preserved remote memory (the temporal gradient of amnesia).

In contrast, patients with cognitive impairment associated with depression, sometimes known as 'pseudo-dementia', may give a very exact account of their memory failures.

Biological (neurovegetative) symptoms may be apparent, such as social withdrawal, apathy and sleep disturbance, all of which may contribute to poor memory function.

Impaired sleep (increased latency to sleep onset, frequent nocturnal waking with difficulty getting back to sleep) is a common finding in the non-demented clinical population, whether or not they have symptoms of depression.

If depression is suspected, a trial of antidepressant medication is indicated, for at least six months.

Dementia is essentially a clinical diagnosis, under current diagnostic criteria, although these are undergoing revision to incorporate biomarkers. With the extremely rare exception of genetically-determined causes, there are no diagnostic tests, but some investigations heighten the index of suspicion.

Of these, cognitive testing, rather than brain imaging, is the most important in primary care. A number of brief cognitive test instruments suitable for primary care are available, although evidence for their use is weak. With the ageing of the population, GPs will increasingly need to become familiar with one of these tests.

The mini-mental state examination has been around for over 30 years but age and education influence the score.

DemTect has the advantages of correcting for age and education, and categorisation of scores into 'normal for age', 'mild cognitive impairment' and 'suspected dementia', which may be helpful in deciding which patients to refer.

The six item cognitive impairment test and GP assessment of cognition are both quicker to perform.

A blood screen for so-called reversible dementias is often recommended (vitamin B12, VDRL, calcium, TFTs) but the pick-up rate is negligible, in line with the falling incidence of reversible dementia.

When to refer
With increasing emphasis on early diagnosis of dementia, it might be argued that threshold for referral should be low.

Certainly every memory complaint should be taken seriously, though a pathological cause will not be found in many cases. The presence of any of the red flags mentioned here should prompt consideration of referral.

Recent NICE/Social Care Institute for Excellence guidance imposes a 'single point of referral' for dementia to memory assessment services, provided by a memory assessment clinic or by community health teams.

Diagnosis of early-onset disease, particularly when other neurological signs are present, may require referral to a neurologist with a special interest.

Dr Larner is consultant neurologist at the Walton Centre for Neurology and Neurosurgery in Liverpool

Differential diagnosis of memory loss
Neurodegenerative diseases

  • Alzheimer's disease +/- cerebrovascular disease (very common).
  • Parkinson's disease dementia/dementia with Lewy bodies (quite common).
  • Frontotemporal dementias (rare).
  • Huntington's disease (rare).
  • Prion diseases (very rare).

Primary psychiatric disorders

  • Depression +/- anxiety (very common).
  • Schizophrenia.
  • Vascular dementias (rare in isolation).
  • Alcohol-related dementia or Wernicke-Korsakoff syndrome.
  • Epilepsy +/- antiepileptic drug therapy.
  • Inflammatory CNS disorders, such as multiple sclerosis.
  • Structural brain disease, such as tumours +/- radiotherapy.
  • Infection, such as sequelae of herpes simplex encephalitis.
  • Primary sleep-related disorders.

'Reversible causes' (very rare)

  • Neurosyphilis.
  • Hypothyroidism.
  • Vitamin B12 deficiency.


Spotting red flags for memory disorders

WHAT are the problems?
Frequent repetition of questions or comments suggests organic amnesia.

Loss of instrumental activities of daily living such as handling finances or medications, travelling by public or private transport, or using the telephone, should arouse concern.

WHY has the patient presented now?
Have problems been worsening over some months? Or has some particular incident triggered consultation?

An acute episode of confusion occurring during febrile illness or post-operatively may be the harbinger of progressive cognitive decline.

WHEN did this happen?
Many years of forgetfulness are less alarming than a history of six to 12 months of progressive decline.

It is worth remembering that pathological causes are much more common in later life, although about 2 per cent of dementia cases in the UK occur before the age of 65 years.

HOW do patient and family cope with the situation?
Have there been repercussions at work or at home because of forgetfulness, for example complaints that work is not being done or even dismissal from work, and others needing to take over the patient's usual household chores?

WHERE do the problems occur?
Are the problems more noticeable in new or unusual situations? Does the patient prefer to be at home, to the extent that social withdrawal has occurred? Has occupational function been impaired?

WHO makes the complaint of forgetfulness?
If the complaints emanate primarily from relatives and carers, while the patient makes little fuss, the clinical index of suspicion should be high.

Likewise if patients are unable to give examples of memory lapses. Patients attending alone very seldom have dementia.


  • Dementia UK. A report into the prevalence and economic cost of dementia prepared by King's College London and the London School of Economics. 2007. l_Report.pdf
  • Dubois B, Feldman H H, Jacova C et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-46.
  • Fisher C A H, Larner A J. Frequency and diagnostic utility of cognitive test instrument use by GPs prior to memory clinic referral. Fam Pract 2007; in press.
  • Clarfield A M. The decreasing prevalence of reversible dementias: an updated meta-analysis. Arch Intern Med 2003;163:2,219-29.
  • National Audit Office. Improving services and support for people with dementia. 2007.
  • NICE/SCIE. Dementia: supporting people with dementia and their carers in health and social care. (Clinical guideline 42) 2006.

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