early markers

Protein in the urine: A warning sign for cognitive decline

December, 2010

Two recent studies indicate that the presence of protein in the urine, even in small amounts, could be a warning sign that a patient may develop cognitive impairment with age.

A six-year study involving over 1200 older women (70+) has found that low amounts of albumin in the urine, at levels not traditionally considered clinically significant, strongly predict faster cognitive decline in older women. Participants with a urinary albumin-to-creatinine ratio of >5 mcg/mg at the start of the study experienced cognitive decline at a rate 2 to 7 times faster in all cognitive measures than that attributed to aging alone over an average 6 years of follow-up. The ability most affected was verbal fluency. Albuminuria may be an early marker of diffuse vascular disease.

Data from 19,399 individuals participating in the Renal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of whom 1,184 (6.1%) developed cognitive impairment over an average follow-up of 3.8 years, has found that those with albuminuria were 1.31-1.57 times more likely to develop cognitive impairment compared to individuals without albuminuria. This association was strongest for individuals with normal kidney function. Conversely, low kidney function was associated with a higher risk for developing cognitive impairment only among individuals without albuminuria. Surprisingly, individuals with albuminuria and normal kidney function had a higher probability for developing cognitive impairment as compared to individuals with moderate reductions in kidney function in the absence of albuminuria.

Both albuminuria and low kidney function are characteristics of kidney disease.

Reference: 

Lin, J., Grodstein, F., Kang, J.H. & Curhan, G. 2010. A Prospective Study of Albuminuria and Cognitive Decline in Women. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

Tamura, M.K. et al. 2010. Albuminuria, Kidney Function and the Incidence of Cognitive Impairment in US Adults. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

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Friends, family detect early Alzheimer's signs better than traditional tests

October, 2010

Cognitive tests only test you at a particular moment in time; early signs of Alzheimer's are more evident in declines in everyday behavior that are most visible to other people.

Confirming earlier research, a study involving 257 older adults (average age 75) has found that a two-minute questionnaire filled out by a close friend or family member is more accurate that standard cognitive tests in detecting early signs of Alzheimer’s.

The AD8 asks questions about changes in everyday activities:

  • Problems with judgment, such as bad financial decisions;
  • Reduced interest in hobbies and other activities;
  • Repeating of questions, stories or statements;
  • Trouble learning how to use a tool or appliance, such as a television remote control or a microwave;
  • Forgetting the month or year;
  • Difficulty handling complicated financial affairs, such as balancing a checkbook;
  • Difficulty remembering appointments; and
  • Consistent problems with thinking and memory.

Problems with two or more of these are grounds for further evaluation. The study found those with AD8 scores of 2 or more were very significantly more likely to have early biomarkers of Alzheimer’s (abnormal Pittsburgh compound B binding and cerebrospinal fluid biomarkers), and was better at detecting early stages of dementia than the MMSE. The AD8 has now been validated in several languages and is used in clinics around the world.

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Specific hippocampal atrophy early sign of MCI & Alzheimer's

January, 2010
  • People with MCI who later developed Alzheimer's disease showed 10-30% greater brain atrophy in two specific regions.

A three-year study involving 169 people with mild cognitive impairment has found that those who later developed Alzheimer's disease showed 10-30% greater atrophy in two specific locations within the hippocampus, the cornu ammonis (CA1) and the subiculum. A second study comparing the brains of 10 cognitively normal elderly people and seven who were diagnosed with MCI between two and three years after their initial brain scan and with Alzheimer's some seven years after the initial scan, has confirmed the same pattern of hippocampal atrophy, from the CA1 to the subiculum, and then other regions of the hippocampus.

Reference: 

Apostolova, L.G. et al. In press. Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal. Neurobiology of Aging, Available online 24 September 2008.

[392] Apostolova, L. G., Thompson P. M., Green A. E., Hwang K. S., Zoumalan C., Jack, Jr C. R., et al.
(2010).  3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI.
Human Brain Mapping. 9999(9999), NA - NA.

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Mental fluctuations may signal Alzheimer's disease

January, 2010

A study has found that mental fluctuations were very rare in those without Alzheimer's, but occurred in nearly 12% of those with very mild or mild Alzheimer’s.

A study involving 511 older adults (average age 78) has found that 11.6% of those with very mild or mild Alzheimer’s (43% of the participants) had mental lapses, compared to only 2 of the 295 without Alzheimer’s. Those with mental lapses also tended to have more severe Alzheimer’s. Although mental lapses are characteristic of dementia with Lewy bodies, this is the first study to look at them in connection with Alzheimer’s. Having mental lapses was defined as having three or four of the following symptoms:

  • Feeling drowsy or lethargic all the time or several times per day despite getting enough sleep the night before
  • Sleeping two or more hours before 7 p.m.
  • Having times when the person's flow of ideas seems disorganized, unclear, or not logical
  • Staring into space for long periods

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Loss of smell may predict early onset of Alzheimer's

January, 2010

Previous research suggesting loss of smell function may serve as an early marker of Alzheimer's disease has now been supported by evidence from genetically engineered mice.

Previous research suggesting loss of smell function may serve as an early marker of Alzheimer's disease has now been supported by a finding that in genetically engineered mice, loss of smell function is associated with amyloid-beta accumulation in the brain, and that amyloid pathology occurs first in the olfactory region. It was striking how sensitive olfactory performance was to even the smallest amount of amyloid presence in the brain as early as three months of age (equivalent to a young adult).

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Damaged protein identified as early biomarker for Alzheimer's

February, 2010

Evidence that levels of damaged tau protein in the cerebrospinal fluid is associated with atrophy in the medial temporal lobe may help diagnose Alzheimer’s early.

A study involving 57 cognitively healthy older adults has found that those who showed decreased memory performance two years later (20 of the 57) had higher baseline levels of phosphorylated tau231 in the cerebrospinal fluid, and more atrophy in the medial temporal lobe. Higher levels of damaged tau protein were associated with reductions in medial temporal lobe gray matter. The finding may be useful in early diagnosis of Alzheimer’s disease.

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Losing muscle mass early sign of Alzheimer’s

April, 2010
  • Previous research has found that unexplained weight loss is an early sign of Alzheimer's. Now a new study has revealed that it is not the overall weight or fat levels that are important, but the loss of lean mass (weight of an individual's bones, muscles and organs without body fat).

Previous research has found that unexplained weight loss is an early sign of Alzheimer's. Now a study involving 140 older adults (60+), of whom half had early-stage Alzheimer's disease, has revealed that it is not the overall weight or fat levels that are important, but the loss of lean mass (weight of an individual's bones, muscles and organs without body fat). This directly correlated with reductions in the volume of the whole brain and of white matter only, along with declines in cognitive performance. The finding is consistent with research suggesting that brain pathology contributes to a decline in body composition, perhaps by disrupting the regulation of energy metabolism and food intake, perhaps through behavioral changes (there is a strong association between loss of muscle mass and reductions in physical activity), or perhaps through a common underlying mechanism, such as inflammation.

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