Memory is the tie that binds together thoughts, impressions, and experiences. Memory function is dependent on several mental or cognitive abilities using several brain systems. Many disease processes can lead to compromise of these systems. When a patient presents to the neurologist with memory loss, the patient or the family is frequently concerned about a neurodegenerative process or dementia. Dementia is often defined as impairment of memory and at least one other cognitive domain that leads to a decline in ability to perform activities of daily living.[1]McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44.
http://www.ncbi.nlm.nih.gov/pubmed/6610841?tool=bestpractice.com
A more simple definition of dementia requires a decline in more than one cognitive domain (e.g., memory, language, visuospatial, or frontal executive function) that interferes with one's ability to function independently.
When evaluating a patient with a concern of memory loss, the following questions should be considered:
Does the patient truly have memory loss or is there another cognitive problem causing the memory disorder?
What is the localization within the brain of the memory problem?
What etiologies are responsible for the memory disorder?
What is the temporal profile for the memory loss: acute (seconds/minutes/hours), subacute (days/weeks), or chronic (many months to years)?
Memory loss versus another cognitive problem
The first consideration is to determine whether the patient truly has memory loss or another cognitive problem.
Memory dysfunction can result from hippocampal lesions (short-term memory loss, e.g., Alzheimer dementia) as well as from lesions of brain structures involved in long-term storage (e.g., semantic dementia). In many cases, memory is encoded properly in the hippocampus, but patients have trouble retrieving the stored memory. This retrieval deficit is typically due to problems with frontal lobe function, often caused by white matter disease.
Some degree of memory loss occurs normally with aging. Normal aging leads to decreased ability for retrieval from a decline in frontal lobe function, but does not impact the activities of daily living.[2]Karlawish JH, Clark CM. Diagnostic evaluation of elderly patients with mild memory problems. Ann Intern Med. 2003 Mar 4;138(5):411-9.
http://www.ncbi.nlm.nih.gov/pubmed/12614094?tool=bestpractice.com
Memory loss becomes particularly concerning when it affects function or activities of daily living.
It is important to differentiate transient, fluctuating disturbances in consciousness due to a delirium from an underlying memory disorder. Many medications can induce confusion or even delirium in the elderly; for example, the greater the number of anticholinergic medications a patient is taking, the greater the risk of hospitalization for confusion or dementia.[3]Kalisch Ellett LM, Pratt NL, Ramsay EN, et al. Multiple anticholinergic medication use and risk of hospital admission for confusion or dementia. J Am Geriatr Soc. 2014 Oct;62(10):1916-22.
http://www.ncbi.nlm.nih.gov/pubmed/25284144?tool=bestpractice.com
The history, exam, and neuropsychological testing can all be helpful in distinguishing a primary memory disorder from a delirium or impairment in retrieval. One relatively large study of hospitalized patients found that a combination of cognitive performance-based tests (Mini Mental State Examination [MMSE]; Mini-Cog) and informant-based tests (AD8; Dementia = [MC]^2) are useful in predicting the risk of delirium.[4]Zeng L, Josephson SA, Fukuda KA, et al. A prospective comparison of informant-based and performance-based dementia screening tools to predict in-hospital delirium. Alzheimer Dis Assoc Disord. 2015 Oct-Dec;29(4):312-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411195/
http://www.ncbi.nlm.nih.gov/pubmed/25350550?tool=bestpractice.com
A Cochrane review of the MMSE for the detection of dementia in community and primary care populations concluded that the MMSE contributes to a diagnosis of dementia but should not be used in isolation to confirm or exclude disease.[5]Creavin ST, Wisniewski S, Noel-Storr AH, et al. Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. Cochrane Database Syst Rev. 2016 Jan 13;(1):CD011145.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011145.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/26760674?tool=bestpractice.com
A systematic review and meta-analysis of 149 studies of cognitive tests for detecting dementia found that the Mini-Cog and the Addenbrooke's Cognitive Examination-Revised (ACE-R) tests were comparable to the MMSE for detecting dementia, while the Montreal Cognitive Assessment (MoCA) was comparable to the MMSE for detecting mild cognitive impairment.[6]Tsoi KK, Chan JY, Hirai HW, et al. Cognitive tests to detect dementia: a systematic review and meta-analysis. JAMA Intern Med. 2015 Sep;175(9):1450-8.
http://www.ncbi.nlm.nih.gov/pubmed/26052687?tool=bestpractice.com
However, a Cochrane review found that there is insufficient evidence to recommend the Mini-Cog as a screening tool for dementia in the primary care setting.[7]Seitz DP, Chan CC, Newton HT, et al. Mini-Cog for the diagnosis of Alzheimer's disease dementia and other dementias within a primary care setting. Cochrane Database Syst Rev. 2018 Feb 22;(2):CD011415.
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD011415.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/29470861?tool=bestpractice.com
A pseudodementia related to depression may result in a clinical presentation suggestive of a memory disorder. Consideration should be made regarding the patient's affective state, because depressed patients may experience diminished concentration, sleep disruption, and mild impairments on delayed recall, which may manifest as a memory disorder.[2]Karlawish JH, Clark CM. Diagnostic evaluation of elderly patients with mild memory problems. Ann Intern Med. 2003 Mar 4;138(5):411-9.
http://www.ncbi.nlm.nih.gov/pubmed/12614094?tool=bestpractice.com
Patients with memory problems or complaints who do not fit a diagnosis of dementia because they are not functionally impaired are often referred to as having mild cognitive impairment (MCI). The deficits in patients with MCI, by definition, are not severe enough to interfere with their normal activities of daily living. The most common form of MCI is amnestic MCI, in which memory is the primary problem. About 50% of patients diagnosed with amnestic MCI will progress to dementia within 5 years. The rate of progression to dementia is about 12% per year.[8]Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999 Mar;56(3):303-8.
http://archneur.ama-assn.org/cgi/content/full/56/3/303
http://www.ncbi.nlm.nih.gov/pubmed/10190820?tool=bestpractice.com
However, MCI can occur in cognitive domains other than memory, including language, visuospatial, and frontal executive (e.g., problems organizing, planning, multi-tasking). Less is known about these other forms of MCI. Many feel that MCI is a precursor or a continuum of dementia and that it should be treated proactively, through prevention of cardiovascular risk factors, an active cardiovascular exercise program, and an active and social lifestyle.[9]Barnes DE, Whitmer RA, Yaffe K. Physical activity and dementia: the need for prevention trials. Exerc Sport Sci Rev. 2007 Jan;35(1):24-9.
http://www.ncbi.nlm.nih.gov/pubmed/17211190?tool=bestpractice.com
Localization of memory problem
The next step in evaluating a patient with memory loss is determining the localization of the memory loss. Memory has traditionally been divided into the following memory systems: episodic, working, semantic, and procedural memory.[10]Budson AE, Price BH. Memory dysfunction. N Engl J Med. 2005 Feb 17;352(7):692-9.
http://www.ncbi.nlm.nih.gov/pubmed/15716563?tool=bestpractice.com
Separate brain structures are responsible for each of these memory types.
Episodic memory: lasts minutes to years, and localizes to the hippocampus and limbic circuits.[10]Budson AE, Price BH. Memory dysfunction. N Engl J Med. 2005 Feb 17;352(7):692-9.
http://www.ncbi.nlm.nih.gov/pubmed/15716563?tool=bestpractice.com
Working memory: a type of memory lasting seconds and involving active rehearsal of information; relies on the integrity of the prefrontal cortex, and the echoic memory in the angular gyrus.[10]Budson AE, Price BH. Memory dysfunction. N Engl J Med. 2005 Feb 17;352(7):692-9.
http://www.ncbi.nlm.nih.gov/pubmed/15716563?tool=bestpractice.com
Semantic memory: typically consists of factual information (e.g., knowing what a certain object is and what it is used for, knowing who was the first President of the US), and localizes to the inferolateral temporal lobes.[10]Budson AE, Price BH. Memory dysfunction. N Engl J Med. 2005 Feb 17;352(7):692-9.
http://www.ncbi.nlm.nih.gov/pubmed/15716563?tool=bestpractice.com
Procedural memory: pertains to driving a car or riding a bike, and involves the basal ganglia, cerebellum, and supplementary motor area.[10]Budson AE, Price BH. Memory dysfunction. N Engl J Med. 2005 Feb 17;352(7):692-9.
http://www.ncbi.nlm.nih.gov/pubmed/15716563?tool=bestpractice.com
The type of memory impairment manifested through the history, physical exam, and neuropsychological testing can give an indication of the localization of the disease process.
Etiology of memory loss
The final consideration is the cause of the memory loss. Neurodegenerative, inflammatory/infectious, metabolic, vascular, traumatic, episodic, and endocrine processes can all produce memory impairment through compromise of the limbic and prefrontal circuits.
