EXPERT ANALYSIS AT SUMMIT IN NEUROLOGY & PSYCHIATRY

WASHINGTON (FRONTLINE MEDICAL NEWS) – Alzheimer’s disease symptoms can be managed with simple algorithms that include ruling out other physiologic concerns and making some lifestyle modifications, according to an expert.

“These approaches are neither hopelessly complicated nor random,” Richard Caselli, MD, said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

Key to diagnosis and management is to understand the differences between Alzheimer’s, dementia, and nondisabling cognitive impairment. “Alzheimer’s disease is the most common cause of dementia, but it is not synonymous with dementia,” said Dr. Caselli, a neurologist at the Mayo Clinic in Scottsdale, Ariz. “Dementia is not memory loss alone but the disabling impairment of multiple cognitive functions.”

Mild cognitive impairment typically means that a patient is still able to conduct his or her activities of daily living despite having memory (or other cognitive) problems.

Although it is possible for a traumatic event such as a family upset, hip replacement surgery, or an infection, to provoke signs of cognitive impairment, it is not usually “down to one day where all hell broke loose and ever since then, [the patient] hasn’t been the same,” Dr. Caselli said. “There are a lot of different reasons why a person can have cognitive difficulty, although with degenerative causes of dementia, it is a gradual onset problem.”

Alzheimer’s disease has a lengthy preclinical phase and can take as long as 15 years (or more) to finally present with symptoms of memory loss after onset, he added.

Changes in behavior, sleep

Behavioral changes in the patient, such as increasing paranoia, delusional states, aggression, and agitation, are an especially problematic aspect of the disease, Dr. Caselli said. Medications such as atypical and typical antipsychotics are off label, but can be effective in helping to manage psychosis and agitation, he said. Antipsychotic medications carry black box warnings from the Food and Drug Administration for use in the elderly, highlighting an increased risk of sudden death, especially in patients with underlying cardiac problems. Dr. Caselli said that, anecdotally, he had not yet seen any such severe adverse events when using atypical antipsychotics in this population, but vigilance should nonetheless be maintained. He also mentioned that pimavanserin, a selective serotonin 5-HT2A inverse agonist, recently was approved for psychosis in Parkinson’s disease, but that he so far has not had any personal experience with it.

Changes in sleep patterns also can offer clues to the type of dementia the patient may have. Pay close attention to the presence of any dream enactment behavior that may be a clue for REM sleep behavior disorder , which as been associated with Parkinson’s disease and dementia with Lewy bodies , according to Dr. Caselli.

Addressing other medical concerns such as restless legs syndrome, hypersomnolence, or nocturia can help patients get better sleep, and in turn, improve their overall disposition.

Physiologic concerns

Comorbid medical conditions such as a urinary tract infection, cancer, or end organ failure, as well as postoperative states and polypharmacy, also should be considered as potentially contributing to altered cognition. Although the physical exam for a person with Alzheimer’s disease tends to be normal, there are some types of dementia that might present with visual loss, aphasia, Parkinsonism, or signs of motor neuron disease, Dr. Caselli said.

Particularly in late-stage dementia, if patients have experienced a fracture or recently have had surgery, an abrupt decline in status could indicate they are in severe pain. “They aren’t going to be able to tell you that, though, and you will just have to be sensitive and attuned to that [possibility],” Dr. Caselli said.

Neuropsychological, other tests

A variety of widely available formal and informal tests can help evaluate a person’s orientation, learning and memory, and constructional and spatial abilities, such as accurately drawing the face of a clock. Language skills testing is important, particularly comprehension, which can be more subtle to detect but can prove key to the differential diagnosis and management.

Neuropsychological testing can reveal different patterns of cognitive impairment. For example, tests sensitive to mental or physical speed can help indicate whether a person has vascular dementia or Parkinson’s disease, two forms of impairment that involve slower cognition. Contrast this with people in the beginning stages of Alzheimer’s, who tend to be much less affected on such tests, Dr. Caselli said.

The conventional wisdom is that brain imaging often yields little diagnostic information in Alzheimer’s, but Dr. Caselli showed examples of tumors, strokes, focal atrophy, and amyloid angiopathy, as imaged abnormalities interfering with cognition. “Imaging in dementia is an important thing to do.”

Meanwhile, don’t ignore the basic lab tests such as blood counts, blood sugar, metabolic panels, and so forth. “Most of the time you don’t find these things, but sometimes you do,” Dr. Caselli said, noting that other clinical tests such as those used for a variety of encephalopathies or fungal infections also can be useful. “I am looking for something I can fix, not just reinforce that the 82-year-old man in front of me with a 2-year history of progressive memory loss has Alzheimer’s.”

There is a wide range of other differential diagnoses to consider testing for in the appropriate setting related to vascular, inflammatory, infectious, nutritional, neoplastic, metabolic, and other pathophysiologic processes. Just remember, it isn’t always Alzheimer’s, and because we can’t ‘fix’ Alzheimer’s, it’s important to make sure we have ruled out all other reasonable possibilities,” Dr. Caselli said. Keep in mind there is a lot of mixed pathology in dementia, he added.

Genetic testing can be important in patients with early-onset Alzheimer’s and a family history because there are several known disease-causing autosomal dominant mutations that, if identified in the patient, may have implications for first-degree relatives, including children. Young adult children have important life decisions to make that could be influenced by their own genetic status. Genetic testing is less likely to be helpful in patients with late-onset dementia with or without a family history, because the results will not alter management. Biomarkers can indicate the actual presence of pathology, but at this point, do not offer a reliable time frame for the evolution of symptoms, he said.

Dr. Caselli receives research funding from Merck as well as the National Institute on Aging.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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