Cognitive Disorders and Dementia in Hypertension
Implications for Treatment
Dementia or normal aging?
Cognitive functions may be defined as mental or “thinking” functions, including all verbal and nonverbal cerebral functions involved in the processing of information: learning, memory, perception, association, abstract reasoning, planning, and so on. In normal aging, there is a slight decline of cognitive functions, especially of memory for recent daily-life events (short-term episodic memory). By contrast, dementia denotes a syndrome of persistent cognitive deterioration, severe enough to interfere with daily activities. Some 20% of all people over the age of 80 yr suffer from dementia. There are two major subgroups of dementia disorders: neurodegenerative dementia, including Alzheimer disease; and vascular dementia. The borderlines between no dementia and dementia are not clear cut. Alzheimer disease, and in some cases vascular dementia, has an insidious onset and a slowly progressive course. In early stages of Alzheimer disease, the patient is forgetful but does not otherwise fulfill the criteria for dementia. Thus, the differential diagnosis between normal aging and early dementia is often difficult. Research is now focusing on how to define early cognitive decline, and on attempts to identify potentially treatable risk factors. In our clinical practice, we have, in the last few years, encountered an increasing number of patients with mild cognitive impairment who are asking for treatment to slow down progress of this condition.
Mrs. B: A Common patient
Mrs. B, a former headmaster, age 82, arrives at your practice accompanied by her son. She has been treated for hypertension with hydrochlorothiazide since the age of 60, and has otherwise been quite healthy. Prior to this visit, her son has called you to explain his concern about Mrs. B’s failing memory. During the last couple of years, Mrs. В has grown increasingly forgetful. Now, she has obvious problems, which cause a great distress to her family. She fails to keep appointments, mislays her money and keys, and has difficulties with orientation to time. She has become more inactive, neglects housekeeping, and has stopped seeing her friends. During the interview, Mrs. В appears cheerful with no signs of depression. She admits to being forgetful, but denies that this causes her any trouble. She looks surprised and slightly embarrassed when her son remarks that she called him some 20 times early this morning, each time asking when they should leave for the doctor’s appointment. Mrs. В appears unsure when asked about the names and ages of her grandchildren. She scores 24 of 30 points on the Mini Mental State Examination (MMSE), she cannot tell the date or weekday, she loses concentration when counting backward, and in a test of short-term memory, she cannot remember any of three words. Her blood pressure in the sitting position is 180/100 mmHg.
1. Does Mrs. В suffer from dementia, and, if so, is it Alzheimer disease or vascular dementia?
2. How should her hypertension best be treated?
Alzheimer disease and vascular dementia: changing concepts over time
In the mid-1970s, the artificial dichotomization between Alzheimer disease or presenile dementia, and senile dementia, i.e., dementia with onset after age 65, was abandoned. With this change in concepts, Alzheimer disease became transformed from a rare disease to a major killer, being one of the most common causes of death in the United States. This had an enormous impact on research and clinicians’ interest in dementia. Today, the term Alzheimer disease is commonly used irrespective of whether the patient is age 45 or 90. However, this is an oversimplification, because Alzheimer disease is most certainly a heterogeneous entity, with subgroups still awaiting their definitions. Early onset Alzheimer disease is often linked to genetic factors, such as the presence of the apolipoprotein E e4 (apo e4) allele and other, rare genetic aberrations. The apo e4 allele is overrepresented in elderly Alzheimer disease patients as well, but the risk factor pattern is more blunted. The concept of multi-infarct dementia was replaced in the 1980s by the wider term vascular dementia, covering dementia resulting from any type of cerebrovascular disease. Still some 5 yr ago, Alzheimer disease and vascular dementia were regarded as two separate entities. However, in recent years, it has become clear that late-onset Alzheimer disease and vascular dementia have common pathways. Autopsy series have shown that both pure Alzheimer disease (i.e., without any cerebrovascular disease) and pure vascular dementia (i.e., without concomitant neuropathologic evidence of AD) are extremely uncommon. Furthermore, recent epidemiologic research supports that cerebrovascular risk factors are determinants not only of vascular dementia, but also Alzheimer disease. Dementia after stroke is common and frequently manifests when the cerebral infarct is combined with Alzheimer disease pathology. In a longitudinal population-based study, hypertension predicted Alzheimer disease in very old patients. The combination of atherosclerosis and apo e4 has also been associated with dementia, irrespective of cause. Even in men without dementia free from stroke, high blood pressure in middle age predicted low cognitive functions at the age of 70. Pathophysi-ologic mechanisms may be multifactorial, including silent ischemic lesions and blood-brain barrier dysfunction, which, hypothetically, may trigger β-amyloid deposition and neurodegeneration. A practical conclusion to be drawn from this is that hypertension is a treatable risk factor, in contrast to older age and genetic factors.
Diagnosis of dementia at the family physician’s office
The key to dementia assessment is to get an objective medical history from someone close to the patient. If you suspect dementia, ask the patient if he or she has memory complaints, but remember that loss of insight is common, and many patients with manifest dementia would deny problems. Conversely, many healthy elderly people report forget-fulness, although it does not cause them any trouble. Make sure that the patient brings someone close to him or her at the next visit. Arrange for a private interview with the informant in order to avoid embarrassment in front of the patient. A comprehensive description of the debut and development of different symptoms yields the greatest part of the diagnostic information: When and how did the symptoms start? Ask specifically for treatable symptoms, such as depression, emotional instability, and insomnia, and about practical problems. Typically, Alzheimer disease presents with an insidious onset of impaired recent memory and word-finding ability. Subsequently, memory, thinking, verbal, and spatial functions deteriorate and activities in daily life are affected. Vascular dementia typically starts abruptly in connection with a stroke, sometimes without any other neurologic signs. However, the course of vascular dementia may also be slowly progressive, mimicking Alzheimer disease. All patients with cognitive disturbances, irrespective of age. This basal assessment includes medical history, physical examination, and laboratory tests in order to exclude hypo- and hyperthyreos, hyperparathyroid-ism, vitamin B12 deficiency, and other treatable conditions.
There are numerous cognitive tests. The MMSE is the most widely used screening instrument for cognitive disorders. Another simple test, sensitive to visuospatial disturbances, is to ask the patient to draw a clock, set at a specified time. Even more sensitive and specific are relevant questions concerning family, current activities, and details of earlier life such as occupation and childhood. Computed tomography (CT) or magnetic resonance imaging (MRI) are valuable complements, and are mandatory in the case of rapid progress, and if a chronic subdural hematoma or a brain tumor are suspected. Conversely, neuroimaging is not always necessary in the assessment of very old patients with a history of slowly progressive dementia over several years.
Table Assessment of Dementia in Old Patients
| 1. Interview |
| Symptoms: cognitive, emotional, or behavioral? |
| Onset: sudden or insidious? |
| Course: slowly progressive or sudden deterioration? |
| 2. Physical examination |
| Neurological examination |
| blood pressure, cardiopulmonary system |
| 3. Laboratory tests |
| B-Hb, B-SR, b-glucose, s-creatinine, s-calcium, s-TSH, s-vitamin BJ2 |
| 4. Cognitive testing |
| Relevant questions |
| MMSE, Clock-Drawing Test, etc. |
| 5. Neuroimaging CT or MRI |
How to treat hypertension in dementia
The main reason to treat hypertension in people ages 80+ is to prevent stroke. Stroke is a powerful predictor of dementia, and recent studies point to the fact that hypertension contributes to Alzheimer disease and dementia, irrespective of stroke. Therefore, an optimal antihypertensive treatment hypothetically may prevent or postpone cognitive decline. There are still no clear guidelines regarding antihypertensive treatment in patients over the age of 80. However, it is reasonable to extrapolate the results from trials in patients ages 70-80. Hence, the target blood pressure should be <160/<90 mmHg, if this can be reached without adverse drug effects. It is mandatory to measure blood pressure in both the supine and standing positions in order to avoid orthostatic hypotension, dizziness, and falls. Of course, other risk factors, concomitant disorders, and patient compliance should also be considered in the choice of therapeutic strategy.
In patients with manifest dementia, we do not know what the optimal blood pressure is. Advanced dementia, irrespective of cause, is often accompanied by low blood pressure. Formerly, low blood pressure was considered a cause of dementia. Now, the prevailing opinion is that low blood pressure in most cases is a consequence of the dementia disorder. Possible mediators are weight loss, a sedentary lifestyle, and perhaps more important, lesions in cerebral blood pressure-regulating areas. Frontotemporal dementia, an uncommon neurodegenerative disorder, is often associated with very low blood pressure even early in its course. Still, many physicians hesitate to treat hypertension in very old patients, because they fear adverse effects on cognition from blood pressure lowering. Geriatricians commonly encounter patients with delirium and dizziness, and who suffer falls secondary to low blood pressure in cardiac failure. For the individual physician, adverse effects possibly related to treatment certainly are more obvious than long-term positive effects (i.e., the non-development of target organ damage). In a recent enquiry, Swedish geriatricians were asked for their opinions regarding antihypertensive treatment of very old patients. Almost 40% stated that systolic blood pressure optimally should be > 160 mmHg in an 82-yr-old hypertensive patient. One third of the physicians believed that, compared with a patient without dementia, a patient with dementia would benefit from a higher blood pressure. Similarly, in a study of 300,000 patients in US nursing homes, hypertensive patients >85 yr and patients with cognitive or physical impairment were not treated according to current guidelines.
Assessment and diagnosis
The first step is to obtain a medical history (e.g., interviewing both Mrs. В and her son about the onset and course of cognitive problems). An insidious onset with slowly progressive course suggests Alzheimer disease. By contrast, an abrupt onset or a sudden worsening points to vascular pathology. CT or MRI in elderly patients with dementia are often difficult to evaluate. They may or may not reveal signs of atrophy, cortical or subcortical infarcts, and white-matter lesions. The absence of significant vascular lesions on CT excludes, on the whole, vascular dementia. Conversely, white-matter lesions are common even in the healthy elderly. Thus, this finding does not justify a diagnosis of vascular dementia. If a patient’s cognitive decline started insidiously with no time relationship to a stroke, he or she probably suffers from Alzheimer disease. If neuroimaging shows evidence of cerebrovascular disease, the diagnosis might still be Alzheimer disease, or Alzheimer disease with cerebrovascular disease. In the latter case, the most accurate, although not yet established, diagnosis would be Alzheimer disease of vascular origin.
Implications for treatment
The treatment goal is to achieve a blood pressure of <160/<90 inmHg without adverse effects. First, determine whether the patient takes his or her tablets as prescribed. The patient probably needs to be reminded. Avoid drugs that may cause delirium — β-blockers should not be the first choice for a patient with dementia. Rapid blood pressure lowering and orthostatic hypotension should be avoided. Generally, old patients tolerate better low doses of two or three drugs than a high dose of a single agent. Monitor blood pressure and monitor cognitive functions by interviewing the patient and his or her caregiver about functions. The MMSE could be administered every 6 or 12 mo. The average annual drop in the MMSE in Alzheimer disease is two to four points. With progression of the dementia disorder, blood pressure may decrease, and treatment should be adjusted. In brief, other pharmacologic treatment in dementia may include selective serotonin reuptake inhibitors for emotional disturbances such as depression and irritability. Acetylcholine esterase inhibitors (donepezil, rivastigmine) can improve attention, short-term memory, word-finding ability, and daily activities in mild to moderate Alzheimer disease. Even more important is to supply psychologic and practical support to the patient and his or her family.
Conclusion
Formerly considered a phenomenon of normal aging, during the last two decades dementia has been recognized as a major health problem. Old people commonly regard a failing mind as the most frightening complication of aging. Dementia and cognitive impairment after stroke cause severe disability and suffering for patients and caregivers, and the costs for society will steadily rise because an increasing proportion of the population will reach very old ages. According to recent studies, hypertension and cerebrovascular disease seem to be important factors behind Alzheimer disease as well as vascular dementia. Cerebral target organ damage in hypertension is no longer just a matter of stroke, but also of dementia. Evidence that an optimal treatment may postpone some cases of dementia has been reported recently from the Systolic Hypertension in Europe trial. Therefore, antihypertensive treatment of old patients should be given very careful attention. At present, however, neither science nor evidence-based medicine can tell what the optimum blood pressure is in old patients with cognitive decline. Treating very old hypertensive patients is a great challenge: Will we succeed in protecting our patients from stroke as well as dementia?
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