Mar 182011
 

Last month, researchers Francisco Lopera and colleagues reported in the journal Lancet Neurology that they were able to capture a clear decline in cognition starting in people’s early 30s in the largest-known population with autosomal-dominant (inherited) Alzheimer’s disease. They define an earlier disease stage prior to what is called pre-MCI, in effect pushing the line of detectability back toward younger ages by some four years.

Two other papers go in the same direction. Last year in the journal Brain, Mario Parra and colleagues published a new test that appears to detect a specific visual memory deficit perhaps even earlier, at ages when mutation carriers perform as well as controls on standard neuropsychometric tests. And in last December’s Annals of Neurology, Yakeel Quiroz and colleagues report the first of what is expected to be a wave of preclinical brain imaging findings. Carriers in their thirties, while still performing the memory test at hand as well as non-carriers, push their hippocampus harder to achieve that parity.

Together, these three papers push back the preclinical phase of Alzheimer’s that is detected by neuropsychology and imaging. They characterize the 20 to 15 years prior to symptoms of dementia.

Each of the previous familial Alzheimer’s disease studies was small. In this paper by Lopera and colleagues, the Colombian scientists retrospectively analyzed descendents of the largest-known cohort of autosomal-dominant Alzheimer’s, including 1,784 patients age 17 to 70 who came to Lopera for treatment and research between 1995 and 2010. This study is by far the biggest study of its kind. Four hundred forty-nine people carried the mutation. Four hundred ninety-nine non-carriers served to establish normal parameters on the battery of cognitive tests that the scientists administered to the participants at follow-ups every other year where possible. The studies are helping us get a better sense of the continuum of Alzheimer’s disease, from its asymptomatic stage into the mild cognitive impairment/prodromal stage, followed by the well characterized mild, moderate and severe dementia stage.

Michael S. Rafii, M.D., Ph.D.
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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Feb 102011
 

Dear Readers,

I often am asked about whether behavioral or personality “traits” are related to cognitive functioning. Specifically, can they “predict” if someone will transition from mild memory trouble ( i.e. Mild Cognitive impairment-MCI) to dementia? Part of this question was addressed in a recent article by Chan and colleagues in the American Journal of Psychiatry.

Participants in this study came from an ongoing epidemiological survey on MCI and dementia conducted in Hong Kong. In Phase 1 of this study, a total of 6100 persons were given the Cantonese version of the Mini Mental State Examination (MMSE) and an abbreviated subjective memory inventory for the Chinese (AMIC). Persons who had scores above the cut of dementia but with memory complaints were invited to participate in Phase 2. These persons were then evaluated by a geriatric psychiatrist, had additional cognitive testing performed to ascertain the Clinical Dementia Rating (CDR) score and were diagnosed with MCI (based on the Peterson criteria) or having no cognitive impairment. Neuropsychiatric symptoms were assessed using the Chinese version of the Neuropsychiatric Inventory (NPI). As is typical with the NPI, symptoms evaluated included a variety of behaviors such as delusions/hallucinations, agitation/aggression, depression, anxiety, euphoria/elation, apathy/indifference, changes in motor behavior, night time behavior disturbances and changes in appetite and eating behavior.

Of the 788 persons who participated in this study, 388 were classified as having MCI and the remainder had normal cognitive function. The MCI group was older (74.5 y vs. 70.2y), had a higher preponderance of women, and had less education (3.6 y vs. 5.6y) compared to the normal cognitive function group. Roughly 36% of those with MCI and 29% of those with normal cognitive function exhibited one or more neuropsychiatric (NP) symptoms. Analyses were done to determine whether having neuropsychiatric symptoms predicted MCI or normal cognitive status. Although nighttime behaviors, apathy and anxiety were the commonest symptoms among persons with mild cognitive impairment (MCI), agitation, apathy and irritability were more prevalent in persons with MCI compared to persons with normal cognition.

Few population based studies have examined the association of behavioral symptoms to the prevalence of NP symptoms in a group of community dwelling older persons and even fewer have addressed these changes in racially and ethnically diverse populations. This study attempts to shed more detail on the behavioral symptom profiles of persons with MCI. The fact that some of the behavior symptoms were noted in the MCI group and not in persons with NCI may suggest that these behaviors are related to specific cognitive deficits.

Thus, NP symptoms could be thought of as a non cognitive marker of MCI and in turn could alert the health professional that a cognitive deficit may be present, which with progression, would lead to a impaired cognitive and motor function, caregiver burden, and worsening of quality of life. More studies, such as this one are needed in the Asian community which may in turn facilitate earlier treatment of cognitive impairment in later life.

Here are three articles you can refer to, to learn about this particular study or the latest research on behavior symptoms and mild cognitive impairment:

Chan WC, Lam L, Tam C, et al. Prevalence of Neuropsychiatric Symptoms in Chinese Older Persons with Mild Cognitive Impairment- A Population Based Study. Am J Geriatric Psychiatry 2010

Lam C, Tam WC, Lui WC et al: Prevalence of Very Mild and Mild Dementia in the Community Dwelling Chinese Older Persons in Hong Kong. Int Psychogeriatrics 2008

Lyketsos CG, Lopez O, Jones B, et al: Prevalence of Neuropsychiatric Symptoms in Dementia and Mild Cognitive Impairment: Results From the Cardiovascular Health Study. JAMA 2002; 288: 1475-1483

Thanks for reading.

Neelum T. Aggarwal, M.D.
Steering Committee Member, ADCS
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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