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Tuesday, February 22, 2011

Depressive Symptoms in Women Aged 65 years and older Associated with MCI and Dementia



Dear Readers,

As I discussed in an earlier blog post this month, the association between behavior and/or personality traits to developing dementia is a hot topic, and one that I am asked to discuss frequently. Depression, in particular, arouses a lot of interest, as many studies have shown an association between depression and poor physical, social and cognitive functioning. The latest study from the Women's Health Initiative Memory Study (WHIMS) examined whether depressive symptoms in post menopausal women would increase the risk of developing mild cognitive impairment and/or dementia.

The Women's Health Initiative (WHI) is a multisite population-based study that assessed the risk and benefits of hormone therapy in healthy postmenopausal women. The WHIMS, was designed to examine the effect of post menopausal hormone therapy on cognition and memory in healthy women aged 65 and older at the study baseline. A total of 7,497 community dwelling post-menopausal women were enrolled in WHIMS. They were aged 65y to 79y at enrollment and were free of Mild Cognitive Impairment (MCI) and dementia. Analyses for this study were based on the 6,376 ( 85%) WHIMS women who completed: (1) a six item Center for Epidemiologic Studies Depression Scale (CES-D), (2) a two item National Institute of Mental Health's Diagnostic Interview Schedule (DIS) and (3) attended at least one follow up visit.

Typical questions asked on the CES-D were whether (1) the participant felt depressed (blue or down), (2) had restless sleep (3) enjoyed life (4) had crying spells (5) felt sad and (6) felt that people disliked the participant. The two questions from DIS asked whether in the past two weeks or more if the participant felt sad, blue or depressed and whether if they had for two or more years feelings of depression/sadness. Other baseline data included demographic information, medical history, lifestyle variables including physical activity and body mass index (BMI). Cognitive testing was measured using the Modified Mini Mental State Examination (3MS) at baseline and yearly after that.

The protocol for assessing MCI and dementia was divided into four phases that included administering to all participants a screening exam for cognition, a more in-depth cognitive battery, and then an assessment by a physician experienced in diagnosis dementia. If a participant was suspected of having dementia, they underwent the typical "work up" for dementia and that included a brain scan and laboratory blood tests. The physician then provided the final diagnosis of the type of dementia.

Of the 6,376 women included in these analyses, 508 met criteria for having depression. Women with depressive disorder were more likely to be African American, widowed, separated or divorced; had lower education, income, and global cognitive function. A total of 216 participants (3.4%) developed MCI , 102 (1.6%) developed dementia of any type and 285 (4.5%) women developed MCI or probable dementia during follow up. Those women who had depressive symptoms at baseline, were found at follow up (mean 5.4 years) to have a greater risk of developing subsequent MCI and incident dementia compared to those who were not depressed. These associations did not change after controlling for lifestyle variables, cardiovascular risk factors, cerebrovascular disease or antidepressant use.

Few population based studies have examined the association of depression to development of MCI and dementia in women. This study is the first to examine these associations in a large group of post menopausal women. Other notable strengths of this study include its large and multiethnic sample size, drawn from diverse communities across the US. These findings suggest that depression may indeed be a risk factor for dementia in women, and that adequate screening and possible intervention may prevent the onset of cognitive decline and dementia.

Here are 3 articles you can refer to for learning about this particular study or the latest research on depression, women and cognitive impairment:

Goveas JS, Espeland MA, Woods NF et al: Depressive Symptoms and Incidence of Mild Cognitive Impairment and Probably Dementia in Elderly Women: The Women's Health Initiative Memory Study. J Am Geriatr So 59: 57-66, 2011

Dal Forno G, Palermo MT, Donohoue JE et al. Depressive symptoms, sex, and risk for Alzheimer's Disease. Ann Neurol 2005; 57: 381-387

Yaffe K, Blackwell T, Gore R et al. Depressive symptoms and cognitive decline in non demented elderly women: A prospective study. Arch Gen Psychiatry 1999; 56: 425-430.


Thanks for reading.


Neelum T. Aggarwal, MD
Steering Committee Member, ADCS
Rush Alzheimer’s Disease Center
Rush Institute for Aging
Chicago, IL














 
Author: Neelum Aggarwal MD at 10:32 AM 0 Comments

Wednesday, February 16, 2011

Potential Link Between Hearing Loss and Alzheimer's Disease


Adults who experience hearing loss may face a higher risk of dementia and perhaps Alzheimer's disease than those who don't suffer hearing loss, new research published in the journal Archives of Neurology suggests. And the greater the loss, the greater the risk.

The researchers looked at the potential association between hearing loss and dementia as part of the Baltimore Longitudinal Study on Aging of 639 men and women between the ages of 36 and 90, none of whom had dementia at the start of the study in 1990. Cognitive and hearing tests were conducted over a four-year period, followed by patient tracking through 2008 (for an average of about 12 years) to monitor for signs of dementia and/or Alzheimer's.

125 study participants were diagnosed with "mild" hearing loss, while another 53 had "moderate" loss, and six had "severe" loss. Ultimately, 58 patients were diagnosed with dementia, of whom 37 had Alzheimer's disease.

By cross-referencing their data, the researchers found that mild hearing loss was linked to a slight increase in dementia risk, but the risk increased noticeably among those with moderate and severe hearing loss. For participants 60 and older, more than 36 percent of dementia risk was linked to hearing loss, the study said.
The worse the hearing loss, the worse the risk for Alzheimer's as well. For every additional loss of 10 decibels of hearing capacity, Alzheimer's risk appeared to go up by 20 percent.

Among the suggested explanations was the notion that hearing loss is merely a sign that someone is not aging very successfully from a biological perspective. Therefore, it would stand to reason that the health of that person's brain is also declining with age. Another thought was that hearing loss might be the result of neural damage affecting the neurological processing of auditory signals. Finally, some suggested that hearing loss can lead to social withdrawal, and that low levels of social engagement have been shown to increase risk for Alzheimer's disease.

The important issue however, is that hearing loss by itself, even with a healthy brain, can also greatly interfere with daily activities. Each of these explanations will require further study to better understand the association between hearing, its loss and cognitive function.


Michael S. Rafii, MD, PhD
Director, Memory Disorders Clinic
Associate Medical Director, Alzheimer's Disease Cooperative Study
University of California, San Diego
 
Author: Michael Rafii MD, PhD at 4:06 PM 0 Comments

Thursday, February 10, 2011

Protein Aggregation and AD


Dear Readers,

Protein aggregation underlies several neurodegenerative diseases such as Alzheimer's, Huntington's chorea or Parkinson's. Researchers in Germany have now discovered a fundamental mechanism which explains how toxic protein aggregation occurs and why it leads to a widespread impairment of essential cellular functions.

The results were published last month in the journal Cell (Jan. 7, 2011). To fulfill their different functions, proteins have to acquire the correct three-dimensional structure. In other words, polypeptides have to fold first. Molecular chaperones, a diverse group of conserved proteins, have specialized to assist other proteins during their folding. If the chaperones fail, misfolding and aggregation of the newly synthesized and pre-existing proteins might occur. In the worst case, this results then in neurodegenerative diseases, such as Alzheimer's, Huntington's chorea or Parkinson's. Alzheimer's disease, for example, develops because the A-beta and tau proteins aggregate, which leads to neuronal dysfunction and cell death.

Researchers in the Department of Cellular Biochemistry at the Max Planck Institute of Biochemistry have now established a novel experimental model aimed at elucidating cellular protein misfolding and discovered why the misfolding and aggregation are deleterious for cells. They prepared several artificial aggregating proteins without any biological function and introduced them into cells. These model proteins clumped together, coaggregating many natural proteins and, in that way, disturbing their function. The researchers discovered that the affected proteins share certain structural characteristics which predispose them for the co-aggregation. With this knowledge in hand, new techniques may target abnormal aggregation and slow down progression of these diseases.

**Heidi Olzscha, Sonya M. Schermann, Andreas C. Woerner, Stefan Pinkert, Michael H. Hecht, Gian G. Tartaglia, Michele Vendruscolo, Manajit Hayer-Hartl, F. Ulrich Hartl, R. Martin Vabulas. Amyloid-like Aggregates Sequester Numerous Metastable Proteins with Essential Cellular Functions. Cell, 2011; 144 (1): 67


Michael S. Rafii, MD, PhD
Director, Memory Disorders Clinic
University of California, San Diego
 
Author: Michael Rafii MD, PhD at 8:41 AM 0 Comments

Friday, February 04, 2011

Behavioral symptoms and Mild Cognitive Impairment in older Chinese persons


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 3 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 Geriatr 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 Psychogeriatr 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, MD
Steering Committee Member, ADCS
Rush Alzheimer’s Disease Center
Rush Institute for Aging
Chicago, IL
 
Author: Neelum Aggarwal MD at 10:12 AM 0 Comments

Wednesday, February 02, 2011

Antidepressants and Amyloid


A recent presentation on antidepressants and brain amyloid at the Fifth annual Human Amyloid Imaging Conference in Miami created great interest.

Dr. Yvette Sheline of Washington University showed that among 186 cognitively normal elderly research volunteers who had undergone a PIB-PET scan, those who had taken antidepressant medication in the past five years had less brain amyloid. The longer these volunteers had been taking antidepressants, the less amyloid they had. The volunteers were otherwise closely matched in age, ApoE and other factors that might affect their amyloid load.

The antidepressants were in the family of selective serotonin reuptake inhibitors. This recent finding suggests that serotonin signaling might affect amyloid deposition.The human studies were prompted by earlier results in mice. Previously, researchers had found that both citalopram and fluoxetine, as well as direct infusion of serotonin, slashed soluble brain Aß levels by a quarter to a third. It is believed that depletion of serotonin with age may increase the likelihood of diseases that affect both memory and mood.

Further studies are planned to confirm these findings.


Michael S. Rafii, MD, PhD
Director, Memory Disorders Clinic
University of California, San Diego
 
Author: Michael Rafii MD, PhD at 3:50 PM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.