Chronic Memory Loss

Memory loss that develops over several months to years is most commonly seen in older adults and often prompts concern about the possibility of Alzheimer disease. However, other conditions should also be considered; a thorough history should investigate medication use, psychiatric symptoms, sleep disorders, and signs of systemic illness. Focal findings on neurologic examination, or neurologic symptoms beyond just memory loss, should prompt neuroimaging.

A.

Memory impairment in older adults is often due to medications that may affect both attention and memory. Anticholinergic medicines, such as meclizine, diphenhydramine, and oxybutynin, can impair memory in otherwise cognitively normal older adults, as may benzodiazepines and other sleep aids. Discontinuation of these medicines and reassessment is appropriate in this context.
B.

Depression and anxiety are common causes of memory loss. Both are associated with reductions in attention and concentration, which, in turn, diminish memory encoding and retrieval. At its extreme, depression has been associated with “pseudodementia.” Note, however, that even with successful treatment, many such patients go on to experience progressive cognitive decline, suggesting mood disturbances may have “unmasked” an underlying neurodegenerative process. Treatment with antidepressants and antianxiety medications, particularly those without cognitive side effects such as selective serotonin reuptake inhibitors, should be pursued; consider psychiatric consultation depending on the clinical context and response to treatment. Reassess patients for cognitive improvement in the context of improved mood or anxiety. Given the relatively slow time course of improvement in depression or anxiety, psychiatric evaluation and treatment are often done in parallel with workup for other causes of memory loss.
C.

Poor sleep is associated with daytime fatigue and also reduces attention and concentration with predictable negative consequences on memory. Sleep, particularly slow wave, is also critical for memory consolidation. Ask patients and their partners about daytime sleepiness and sleep habits. Snoring and gasping for air suggest obstructive sleep apnea, which can be effectively treated with continuous positive airway pressure. Obese patients are at higher risk. Acting out one’s dreams, including conversations and physical movements, reflects impaired reduction in muscle tone during rapid eye movement sleep and is a predictor for the presence or development of Lewy body spectrum disorders, including Parkinson disease and Lewy body dementia. Insomnia may have a psychiatric etiology, and such sleep deprivation can also contribute to poor memory. In all cases, an overnight polysomnogram may be necessary for diagnosis.
D.

If none of the above potentially reversible causes of memory loss are found, brain magnetic resonance imaging (MRI) should be performed and B12, methylmalonic acid, and thyroid function tested. Suspicion for B12 deficiency should be heightened in the setting of large fiber neuropathy and macrocytic anemia, though cognitive symptoms may exist without these findings. Weight gain, cold intolerance, and cognitive slowing suggest hypothyroidism.
E.

Memory loss over weeks to months may be associated with a subdural hematoma, particularly in older adults after a fall. Focal findings are often absent on examination, and memory loss is often driven by poor concentration and executive function. A frontal lobe mass may affect memory encoding and retrieval, and is also often associated with other frontal lobe cognitive manifestations. Brain MRI reliably identifies these abnormalities.
F.

Memory impairment associated with a slow, magnetic gait and urinary incontinence suggests normal pressure hydrocephalus. The cognitive profile is typically characterized by slowing of processing speed and memory loss on the basis of poor encoding and retrieval, but normal memory storage (i.e., recall tends to be worse than recognition memory). Brain imaging shows enlarged ventricles. Confirmation of the diagnosis depends on demonstrating clinical improvement after large-volume lumbar puncture.
G.

Vascular dementia presents with a cognitive profile similar to normal pressure hydrocephalus (see section F). MRI will show extensive microvascular disease. Note that most with vascular cognitive impairment have a slowly progressive course and not the step-wise progression that is classically described.
H.

Prominent and slowly progressive memory loss in a temporal limbic pattern is a hallmark of Alzheimer disease. This form of memory loss reflects a loss of information over time supported by impaired memory recall and recognition memory. Other cognitive domains, including executive function, language, and visuospatial processing, tend to be less affected early in the course of disease. MRI demonstrating hippocampal and lateral parietal atrophy supports the diagnosis, though a normal MRI does not exclude Alzheimer disease. In addition to Alzheimer disease, a variety of other neurodegenerative conditions are associated with memory loss, but usually have impairment in other salient nonmemory cognitive domains (e.g., semantic dementia) or other associated neurologic features (e.g., asymmetric dystonia in corticobasal degeneration).