Memory Loss

Everyone is afraid of getting Alzheimer’s Disease.  As such, it’s common for some people to seek care for any degree of perceived memory change.  But mental status testing, especially for cognitive function, is complex and time-consuming.  As such, we need to be discriminating in whom we work up, & whom we refer.

First Step, as always, is to define the chronology.  Acute memory loss is alarming, and requires rapid diagnosis.  This may be best conceptualized as Altered Mental Status, for which we have a handy differential diagnosis and summary work-up already posted.  See also our topics Loss of Consciousness (LOC-1 and LOC-2) for patients with episodes of amnesia.

Chronic but profound memory loss, especially if it includes loss of orientation, is Dementia.  Most will be Alzheimer’s Disease, but there are some other diagnostic possibilities we’ll discuss below.

But from now on, let’s say we’re dealing with a person who’s fully oriented x3, but just thinks that they’re forgetting things.  At the first visit, I try to get a sense of the degree to which this happens, how recent it’s occurred, and especially if it’s progressive.  I seek examples of what they’ve forgotten.

  • Does it interfere with ADLs and job?
  • Is it dangerous? Like forgetting food cooking on stove, losing keys, getting lost, serious financial errors.
  • Do they forget things that you [the reader] & I would never forget, no matter how preoccupied (e.g. names of significant others)

This doesn’t take too long. It sets a tone for my concern, and leads us to some KEY POINTS —

1.  People with Dementia rarely present on their own with memory loss, because they don’t realize or remember what they’re forgetting. Families and Friends bring them in. This is who needs to provide the history, including behavior changes.

2.  “Mild Cognitive Impairment” (MCI) is an amorphous diagnosis. It’s applied to patients is still able to function in society & life. Some will progress to Dementia, others never will. such patients are often aware of & concerned about their memory loss.

3.  When a patient can articulate their memory loss well, they’re often suffering from Anxiety (including the worried-well) or Depression (or, rarely, Malingering).

No matter what, on the first visit, I obtain an overall history, perform a general physical exam, and in particular a decent neuro exam. If the history occupied too much time, I might postpone the neuro component for a second visit. Key components of history, especially if they correlate temporally to the memory loss, that shouldn’t be forgotten (by the examiner):

  • Head trauma — mandates non-contrast CT to r/o subdural hematoma
  • Medications — mandates trial of discontinuation if at all possible
  • Substances — same as above, though often harder to achieve

The neuro exam should specifically seek out focal deficits (especially in the cranial nerves), and signs of Parkinson’s (resting tremor, fixed facies, shuffling gait, cogwheel rigidity).

There are a few mental status exams that seem to correlate about the same, i.e. around 80-85% sensitivity for dementia depending on cut-off score used, less sensitive for mild dementia. There’s the ubiquitous Mini-Mental Status Exam (MMSE), which is patented, which means that you might get sued for using it [really???].

Then there’s the Mini-Cog, not as well studied, but much quicker & valid regardless of educational level or native language.  It can be completed in 1 to 4 minutes, and employs just 2 tests: 3-minute recall, and clock drawing.  But even better (or at least quicker) is the Animal Fluency Test:  have the patient name as many animals as possible in 1 minute.  A score <15 correlates with dementia.

Another useful strategy questions informants, i.e. friends & family, using the AD8 Dementia Screening Interview.  It and other tools can be accessed through the Alzheimer’s Association.

Finally, a recent study found that measuring the distance at which each nostril can smell peanut butter has high sensitivity & specificity for Alzheimer’s, when the right nostril can detect it 10 cms. further away than the left one can.  After all, dementia is a frontal lobe disease, right where the olfactory nerve head is buried.  Read a news report and an abstract if you’d like.

If cognitive testing is normal, I reassure the patient, though if they seem unconvinced, I might order basic laboratory tests [see below].  If those are normal, and the patient remains worried on follow-up, I explore anxiety & depression if I haven’t yet.

Sleep Deprivation can cause functional memory loss.  I made a “brilliant” diagnosis once; it took me less than 10 minutes, and is in quotes because a  major medical center’s memory clinic missed it.  Click for a link to an (in my mind) unethical anecdote.

Laboratory Work-Up

Once we identify any degree of cognitive dysfunction, the first step is to rule out reversible causes.  Assuming both general & neuro exams are normal, I order a few basic lab tests:

  • CBC
  • Metabolic Panel
  • Urinalysis
  • TSH
  • Vitamin B12 level
  • ??? RPR and treponemal test (FTA-ABS or TP-PA) for syphilis [but see below]
  • ??? HIV antibody

Regarding the B12 level, if it comes out normal but in the lower quartile of values, I also order Methylmalonic Acid (MMA) and Homocysteine levels.  These intermediaries are necessary for B12 utilization, and are thus elevated when there’s not enough vitamin around.  A person can have serious neurocognitive sequelae from B12 deficiency without being anemic or macrocytotic.  If B12 levels are well-within normal range, I might order these tests for rapidly-progressive dementia.

However, it should be noted that the vast majority of laboratory tests ordered for dementia return normal.  So on the one hand, cost-effectiveness could be considered nil.  That of course gets weighed against the horrors of missing a reversible cause.

An 87-year-old Mexican man, profoundly demented and diagnosed with Alzheimer’s for over 20 years, was brought in by his son as a new patient.  Apparently other family out-of-state got worn out, arrived unannounced to hand him off, and promptly fled.  Medical records were hard to come by, so I ordered labs, & his RPR came out 1:4.

Did he have late neurosyphilis all that time (see our posting Syphilis for an in-depth discussion)?  Impossible to say.  It would have required a lumbar puncture, which would likely have required general anesthesia, and treatment wouldn’t have reversed anything.  Placement was unfortunately unfeasible, since he was uninsured and undocumented, and waiting lists at our local public long-term care facility are also long.

The American Academy of Neurology does not recommend syphilis testing for dementia; indeed, our local expert, nationally-prominent, has never seen a case of late neurosyphilis.  It’s extremely rare nowadays, likely because during the 20 – 30 years it takes to develop, infected people wind up receiving antibiotics for other indications, which, even if not optimal therapy, wind up working.  But my population includes elderly immigrants who’d never received prior health care in their poor countries-of-origin, so I still screen.  And up to 25% of patients with late neurosyphilis have negative RPR’s, requiring a treponemal test for diagnosis.

HIV-related dementia (known by many synonyms) usually occurs with advanced AIDS, though occasionally in earlier HIV disease if there’s a very high viral load.  It doesn’t truly mimic Alzheimer’s, because more cognition than expected is retained for the profound psychomotor slowing.  If a person has risk factors, or simply never had an HIV test, it’s indicated.


The American Academy of Neurology recommends either a non-contrast CT or MRI at initial work-up, looking for subdural hematomas, cancers, or hydrocephalus (rare).  The non-contrast CT can detect lesions large enough to cause Dementia, but the MRI is more useful for those with Mild Cognitive Impairment, since it can identify temporal lobe atrophy and other patterns predictive of progression to Dementia.

Other experts only image in special cases: rapidly progressive dementia, or <60 y.o.  Certainly anyone with focal neuro findings requires a contrast-enhanced MRI, and those with history of head trauma should get non-contrast CTs for subdurals.

For competent, functional patients with Mild Cognitive Impairment, don’t order an MRI without a discussion.  Reassure them they do not have Alzheimer’s.  Inform them that their impairment may or may not progress.  Ask them if they want to know if they’re high risk of developing it, or simply see what happens in life over the next few years.


I tend to refer all my patients with significant cognitive dysfunction to Neurology.  Perhaps it’s because of my lack of comfort.  But since Alzheimer’s Disease, and other neurodegenerative conditions like Lewy-body or frontotemporal dementia, are irreversible with poor prognoses and major implications, I like a specialist to confirm the diagnosis.

Vascular (aka Multi-infarct) Dementia, occurring among those with cardiovascular risk factors, requires risk-factor modification.  But that would be done for those underlying conditions anyway.  It doesn’t respond to medications used for Alzheimer’s, but frankly, those drugs hardly do much anyway.  The need for precise diagnosis will change if more effective treatment ever appears.  In terms of non-pharmacologic management of dementia, it’s essentially the same for all.

“Memory Loss” Without Objective Findings

Many patients are reassured that their evaluation is normal, including whatever cognitive function screen was done, & neuro exam.  Those who remain unconvinced usually suffer from anxiety or depression.  I often obtain the basic laboratory tests above, since they may be indicated in the work-up of new-onset mood disorders.  I’d only image if I felt the mood or personality changes were significant, not for perceived memory loss with normal findings.


1.  R/O Acute Mental Status Changes (delirium)

Assuming complaint is Gradual Onset Memory Loss

2.  a) Perform a General & Neuro Exam
     b) Perform a Cognitive Assessment (any of below):

If Cognitive Assessment Abnormal

 3.  Order basic Lab tests (work-up / treat abnormalities)
  • CBC
  • Metabolic Panel
  • Urinalysis
  • TSH
  • Vitamin B12 level (if borderline, order Methylmalonic Acid)
  • Consider RPR, treponemal serology (FTA-ABS, TP-PA), HIV test

4.  Consider non-contrast Brain CT

5.  Dementia → Refer to Neurology if desiring specific diagnosis

6.  Mild Cognitive Impairment
  • Consider MRI for prognosis [see text above]
  • Consider referral to Neurology
  • Consider following for progression

If Cognitive Assessment Normal

a) Reassure
b) Consider Lab Tests as in #3 above
c) Explore diagnosis of Anxiety or Depression

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