Dementia

Editor's Note: This issue of In the Clinic has been updated. Prevention Dementia is defined as a decline in cognitive function from baseline. It is a syndrome caused by a variety of disorders, the most common of which are Alzheimer disease, vascular dementia, Lewy body dementia, and frontotemporal dementia. The incidence and prevalence of dementia increase with age. It is estimated that by the year 2047, more than 9 million Americans will have some form of it (1). Institutionalization is ultimately required for many patients with dementia, and 67% die in nursing homes (2). Although there is currently no cure for most forms of dementia, research findings and accumulated clinical experience support a set of practices that serve to maximize the function and overall well-being of patients with dementia and their caregivers. What medical interventions or health behaviors can help patients prevent dementia? Although there are several risk factors for different types of dementia, data supporting the effectiveness of specific preventive measures are limited. Hypertension Untreated hypertension in mid-life and later is a proven risk factor for both Alzheimer disease and vascular dementia (3). A number of randomized, controlled trials (RCTs) have shown that treating hypertension reduces the risk for dementia. A large, placebo-controlled RCT with 2418 participants demonstrated that treating systolic hypertension in patients over the age of 60 years reduced the incidence of dementia by 50%, from 7.7 cases to 3.8 cases per 1000 patient-years (4). Another placebo-controlled RCT with 6106 participants showed that treating hypertension with the angiotensin-converting enzyme inhibitor perindopril with or without the thiazide diuretic indapamide reduced the incidence of recurrent stroke with dementia by 34% and of recurrent stroke with any cognitive decline by 45% in patients with past stroke or transient ischemic attack (5). Hypercholesterolemia and Diabetes Mellitus Hypercholesterolemia, particularly in mid-life, is associated with an increased incidence of both Alzheimer disease and vascular dementia, (6), and case-control studies have shown an association between use of cholesterol-lowering medications and reduced incidence of dementia (7). Diabetes has been shown in both longitudinal cohort and case-control studies to be an independent risk factor for vascular dementia (8, 9). However, as with hypercholesterolemia, there are no trials that demonstrate that treating diabetes prevents dementia. Lifestyle Modifications Cigarette smoking is associated with an increased risk for stroke, although the evidence for an association with Alzheimer disease is mixed (10). Head injury earlier in life has been shown in a number of epidemiologic studies to be associated with dementia later in life (11). Finally, physical inactivity, both in mid-life and later, has been associated with an increased risk for dementia in both retrospective and prospective studies 12, 13). Thus, counseling patients to quit smoking; engage in behaviors to reduce the risk for head injury, such as wearing seat belts and bike helmets; and be physically active may reduce the risk for dementia. Medications Clinicians should regularly review the medication regimens of elderly patients and minimize use of medications that can cause cognitive impairment, such as benzodiazepines, anticholinergics, barbiturates, and other sedative-hypnotics. A number of studies have shown that elderly patients taking benzodiazepines or other sedative-hypnotics perform more poorly on cognitive tests than those not taking these medications (14). Because inflammation is present in the brains of patients with Alzheimer disease and epidemiologic evidence links use of non-steroidal anti-inflammatory drugs (NSAIDs) earlier in life to a lower risk for Alzheimer disease (15), some have questioned whether NSAIDs might prevent dementia. However, prospective studies to date have not shown a protective effect of NSAIDs, and they are not recommended for prevention of dementia (16). Significant epidemiologic evidence links mid-life estrogen use to a lower incidence of dementia later in life (17). However, in prospective prevention trials, including the large Women's Health Initiative Memory Study, use of estrogen plus progestin for prevention of dementia was associated with an increased incidence of dementia, as well as other medical complications (18). Clinical Bottom Line: Prevention Although there are few data to support specific measures to prevent dementia, clinicians should treat cardiovascular risk factors, such as hypertension, hypercholesterolemia, and diabetes, and encourage smoking cessation and regular exercise. They should also counsel patients about avoiding head injury and avoid prescribing medications that can alter cognitive function. Neither NSAIDs nor estrogen should be recommended for prevention of dementia. Screening Should clinicians screen for dementia? The U.S. Preventive Services Task Force concluded that there is insufficient evidence to recommend for or against widespread screening for dementia in elderly patients (19). However, many patients with dementia in the primary care setting, even those in more advanced stages of the disease, remain undiagnosed despite having routine general medical care (20). Moreover, patients referred to dementia specialists after "screening" have been diagnosed at an earlier stage of illness than those referred from physicians or families (21). Therefore, given the high prevalence of dementia and its associated morbidity, the clinician should consider secondary case-finding measures for dementia in elderly patients with unexplained functional decline, deterioration in hygiene, questionable adherence to medication regimens, or new-onset psychiatric symptoms. What methods should clinicians use when looking for dementia? When looking for dementia in elderly patients, clinicians should use a standardized screening instrument together with a brief history from the patient and a knowledgeable informant. The screening instrument should be easy to use, demonstrate high sensitivity, be widely available, and be supported by normative population data relevant to the patient. Two examples of such instruments are the Mini-Mental Status Examination (22) and the Mini-Cog (23). Clinical Bottom Line: Screening There is insufficient evidence to recommend for or against screening asymptomatic people for dementia. However, clinicians should be alert for unexplained functional decline, deterioration in hygiene, questionable adherence to medication regimens, or new-onset psychiatric symptoms in elderly patients and use standardized instruments, such as the Mini-Mental Status Examination or the Mini-Cog, to look for cognitive dysfunction in such patients. Diagnosis What elements of the history are most important in evaluating patients with suspected dementia? Clinicians should use the patient's history to characterize the cognitive deficits, generate a differential diagnosis, and attempt to determine the cause of the dementia. This is best accomplished by identifying medical, neurologic, and psychiatric symptoms that may be clues to the cause of the cognitive problems and detailing their order of appearance, severity, and associated features. In the case of cognitive difficulties, it is mandatory to try to obtain collateral information from a knowledgeable informant, because cognitive dysfunction can impair the patient's ability to serve as an accurate reporter. It is often easier to collect this information, as well as information about psychiatric symptoms, without the patient present. In taking the history, it is critical for clinicians to be knowledgeable about the differential diagnosis and natural history of the most common types of dementia (Table 1). For example, in classic Alzheimer disease, early symptoms are dominated by difficulties with short-term memory, subtle language and visuospatial perception difficulties, and changes in executive function with significant reductions in efficiency and organizational abilities of which the patient may or may not be aware. Symptoms begin insidiously and are slowly progressive. Overall level of alertness remains unimpaired. Patients or families may not label these difficulties as memory problems per se but may instead report multiple repetitions of questions or conversations with no recollection of previous discussions, increased forgetfulness manifested by losing objects or becoming confused while shopping, or simply overall increased disorganization and decreased efficiency. Symptoms are often first noticed or reported at the time of a life change, such as the death of a spouse or a move into a new residence. See the Box for clinical diagnostic criteria for definite and probable Alzheimer disease (24). Clinical Diagnosis of Alzheimer Disease (AD) Definite AD: Clinical criteria for probable AD plus histopathology confirmation Probable AD: Dementia by clinical examination and standardized instrument (e.g., Mini-Mental State Examination) Deficits in >2 areas of cognition Progressive cognitive decline Normal levels of consciousness Onset between age 40 and 90 years No other cause Supportive factors, including positive family history, cerebral atrophy on neuroimagining, normal electroencephalogram and lumbar puncture Table 1. Differential Diagnosis of Cognitive Difficulties Many elderly patients report minor cognitive problems, such as mild forgetfulness, difficulty remembering names, and mildly reduced concentration. In patients without dementia, these symptoms are typically sporadic, do not worsen significantly over time, are easily compensated for, and do not affect function. In contrast, in early dementia, the symptoms insidiously become established as a pattern, worsen over time, are difficult to compensate for, and eventually affect speech fluency and hamper the performance of routine activities, such as meal prepa