‘Normal’ cognitive decline

ARCD is subtle decline in cognitive abilities, such as episodic memory, attention, and time needed to complete complex activities.6,7 Individuals with ARCD might not have subjective memory complaints or objective cognitive deficits, and their ability to live independently may not be compromised.7 The degree of decline in ARCD may be smaller than previously thought.8 Park9 summarizes 4 main mechanisms thought to underlie age-related declines in cognition:

reduced speed of processing

decreased working memory capabilities

declining inhibitory control (eg, impaired complex attentional capabilities)

sensory changes (eg, visual and auditory deficits).

ARCD traditionally is thought to result from predictable changes in the brain associated with aging, such as reduced brain volume in the hippocampus and frontal lobes, loss of myelin, loss of synapses, and cytoskeletal changes.7 However, not all older adults experience ARCD. Some remain highly functional in their later years and continue to actively engage in life well into very old age.6,9

Subjective cognitive impairment

One-quarter to one-half of community-dwelling older adults report subjective cognitive complaints, such as forgetfulness and word-finding difficulties.10 Patients with SCI do not show objective evidence of cognitive impairment on neuropsychological tests and their cognitive problems cause no functional decline.10

Preliminary evidence indicates that SCI may be a harbinger of further cognitive decline. Reisberg et al3 found that compared with patients without SCI, patients with SCI were 4.5 times more likely to develop MCI—cognitive difficulties that can be detected by cognitive tests, but do not cause functional decline—or dementia within 7 years.3 Studies also have suggested that SCI may be a pre-MCI stage of subsequent dementia.11-13 AD generally has a long (10 to 12 years) and progressive prodromal phase before dementia onset and is characterized by successive emergence of cognitive deficits, memory complaints, depressive symptoms, and functional impairment.14

In light of this research, we believe patients with SCI and other risk factors for AD, such as a family history of AD, may be at higher risk of further cognitive and functional decline compared with individuals with ARCD and no AD risk factors. Therefore, patients with SCI and other risk factors for AD (Table 2)15-19 may benefit from annual follow-up to determine if cognitive problems have progressed to MCI or AD.

SCI may be a response to subclinical alterations in neurobiology—a phenomenon known as reverse causality.20 Biomarkers, such as cerebrospinal fluid levels of ß-amyloid and phosphorylated tau, and amyloid imaging using positron emission tomography may help identify AD in SCI patients.21 In these patients, SCI is a misnomer because the cognitive impairment is real—not “subjective”—but current tests are not sensitive enough to detect the cognitive decline the patient has recognized. This group of patients should be differentiated from individuals who may perceive typical cognitive aging (ARCD) as pathologic and complain about it. In the future, biomarkers may help differentiate these 2 groups.

‘Normal’ cognitive decline

ARCD is subtle decline in cognitive abilities, such as episodic memory, attention, and time needed to complete complex activities.6,7 Individuals with ARCD might not have subjective memory complaints or objective cognitive deficits, and their ability to live independently may not be compromised.7 The degree of decline in ARCD may be smaller than previously thought.8 Park9 summarizes 4 main mechanisms thought to underlie age-related declines in cognition:

reduced speed of processing

decreased working memory capabilities

declining inhibitory control (eg, impaired complex attentional capabilities)

sensory changes (eg, visual and auditory deficits).

ARCD traditionally is thought to result from predictable changes in the brain associated with aging, such as reduced brain volume in the hippocampus and frontal lobes, loss of myelin, loss of synapses, and cytoskeletal changes.7 However, not all older adults experience ARCD. Some remain highly functional in their later years and continue to actively engage in life well into very old age.6,9

Subjective cognitive impairment

One-quarter to one-half of community-dwelling older adults report subjective cognitive complaints, such as forgetfulness and word-finding difficulties.10 Patients with SCI do not show objective evidence of cognitive impairment on neuropsychological tests and their cognitive problems cause no functional decline.10

Preliminary evidence indicates that SCI may be a harbinger of further cognitive decline. Reisberg et al3 found that compared with patients without SCI, patients with SCI were 4.5 times more likely to develop MCI—cognitive difficulties that can be detected by cognitive tests, but do not cause functional decline—or dementia within 7 years.3 Studies also have suggested that SCI may be a pre-MCI stage of subsequent dementia.11-13 AD generally has a long (10 to 12 years) and progressive prodromal phase before dementia onset and is characterized by successive emergence of cognitive deficits, memory complaints, depressive symptoms, and functional impairment.14

In light of this research, we believe patients with SCI and other risk factors for AD, such as a family history of AD, may be at higher risk of further cognitive and functional decline compared with individuals with ARCD and no AD risk factors. Therefore, patients with SCI and other risk factors for AD (Table 2)15-19 may benefit from annual follow-up to determine if cognitive problems have progressed to MCI or AD.

SCI may be a response to subclinical alterations in neurobiology—a phenomenon known as reverse causality.20 Biomarkers, such as cerebrospinal fluid levels of ß-amyloid and phosphorylated tau, and amyloid imaging using positron emission tomography may help identify AD in SCI patients.21 In these patients, SCI is a misnomer because the cognitive impairment is real—not “subjective”—but current tests are not sensitive enough to detect the cognitive decline the patient has recognized. This group of patients should be differentiated from individuals who may perceive typical cognitive aging (ARCD) as pathologic and complain about it. In the future, biomarkers may help differentiate these 2 groups.

Hello Amy,

Computerised tests such as CANTAB and Cogstate can pick up subtle changes in cognitive decline in the elderly. The decline is greater in subjects who have amyloid (measured using PET) or certerain genotypes (i.e. BDNF polymorophism). Cognitive domains such as episodic memory, executive function and language are sensitive to decline over time.

Please see our recent paper on this.

All the best,

pradeep

Neurobiol Aging. 2013 Nov;34(11):2457-64. doi: 10.1016/j.neurobiolaging.2013.05.006. Epub 2013 Jun 12.

BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease.

Lim YY1, Villemagne VL, Laws SM, Ames D, Pietrzak RH, Ellis KA, Harrington KD, Bourgeat P, Salvado O, Darby D, Snyder PJ, Bush AI, Martins RN, Masters CL, Rowe CC, Nathan PJ, Maruff P; Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Group.

Author information 1Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia. [email protected]

Abstract

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has previously been implicated in Alzheimer's disease (AD)-related cognitive impairment. We aimed to determine the relationship between BDNF Val66Met and beta-amyloid (Aβ) on cognitive decline, hippocampal atrophy, and Aβ accumulation over 36 months in 165 healthy adults enrolled in the Australian Imaging, Biomarkers and Lifestyle study. In healthy adults with high Aβ, Met carriers showed significant and moderate-to-large declines in episodic memory, executive function, and language, and greater hippocampal atrophy over 36 months, compared with Val/Val homozygotes. BDNF Val66Met was not found to be related to rates of change in cognition or hippocampal volume in healthy adults with low Aβ. BDNF Val66Met did not relate to the amount of Aβ or to the rate of Aβ accumulation in either group. High Aβ levels coupled with Met carriage may be useful prognostic markers of accelerated cognitive decline and hippocampal degeneration in individuals in the preclinical stage of AD.

Copyright © 2013 Elsevier Inc. All rights reserved.

In Germany, in the linical setting, the DemTect test is used to detect kognitiv impairment esp. when MiniMental Test is normal.

Kalbe, E., Kessler, J., Calabrese, P., Smith, R., Passmore, A. P., Brand, M. & R. Bullock, R.(2004). DemTect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia. International Journal of Geriatric Psychiatry, 19, 136–143. PMID 14758579

Detailed questioning about anxiety and depressive symptoms reveals substantial worries about future cognitive decline and some concerns about her finances and her husband’s health. Ms. F says she occasionally feels down and has low energy but denies other depressive symptoms. She reports no sleep disturbances—including snoring and daytime sleepiness, which could indicate obstructive sleep apnea—which her husband confirms. Ms. F takes levothyroxine for hypothyroidism, atenolol for hypertension, aspirin and clopidogrel for coronary artery disease, and atorvastatin for hyperlipidemia. In addition, she provides a long list of over-the-counter (OTC) supplements—ginkgo, huperzine, ginseng, phosphatidylserine, B1, B12, folate, vitamin D, alpha-lipoic acid, and vinpocetine—that she takes to “protect” her brain from AD.

Subjective cognitive impairment (SCI) in older persons is a common condition with a largely unclear prognosis. Many older adults (age ≥65) express concern about mild cognitive problems—“senior moments”—such as word-finding difficulties and forgetfulness.1 Individuals may wonder if walking into a room only to forget why might be the first sign of dementia. Some older adults try to counteract these memory problems by engaging in brain exercises—including costly computer games—and taking OTC “brain-enhancing” vitamins, herbal remedies, and other supplements.

Although some clinicians may view SCI as benign, that is not always true (Table l).2-5 This article discusses the clinical significance of these mild cognitive complaints by examining:

Clinical Point

Patients with SCI do not show objective evidence of cognitive impairment and their cognitive problems cause no functional decline

age-related cognitive decline (ARCD)

SCI

how SCI can be differentiated from more serious conditions, such as mild cognitive impairment (MCI) and early stages of AD and other dementias.

We also will discuss assessing and treating cognitive complaints. Although distinctions between SCI and ARCD may be controversial, evidence suggests clinicians need to adopt a more nuanced clinical approach.

Fariborz, thank you so very much for your response, it has been very helpful to read. Are both comments from a published research paper? If so which one please? I agree it is a controversial area, and also a very important area regarding the possibility that SCI is a pre-MCI stage of subsequent dementia. Thank you again.

Pradeep, thank you also for your response. I will certainly be looking into the tests that you mention. I have located the paper you recommend, thank you very much.

Gee, thank you for pointing me in the direction of the DemTect, I very much appreciate it.

Your well come

Amy, I also attacched another paper of ours looking at cognitive decline in SCI.

Thank you so much! I look forward to reading it :-)

I think this will remain a difficult area of assessment due to overlap of so many factors affecting higher level cognitive performance. By the way, where is the acronym "SCI" used with respect to cognitive impairment. It has long been the acronym for Spinal Cord Injury, and this new usage could be confusing (especially since folks with SCI can also have concomitant TBI). : >)

Hi Nancy, thank you very much for your response. Subjective cognitive impairment, thus SCI, from what I know of has been referred to as such for a number of years, when from exactly I don't know sorry. I agree with your point that it overlaps with spinal cord injury and therefore could cause much confusion. Recently the term subjective cognitive decline has been put forward, suggesting that the term 'decline' is more appropriate than 'impairment'. It is an under researched area, and a very complex one at that. So many factors impact on it....specifically my team and I are interested in those people who go to the memory clinic, do not display any signs of an objective memory impairment, do not display any physical/medical abnormalities, no mental health problems etc...but still have a subjective cognitive problem. I agree it will always be a difficult area of assessment, but the more we know about it neurologically, cognitively, psychologically etc...the closer we may get to understanding what it is and how we can measure it.

Regarding some current research on cognitive measures for "early detection", see the following recent review article:

Dorene M Rentz , Mario A Parra Rodriguez , Rebecca Amariglio , Yaakov Stern , Reisa Sperling and Steven Ferris. Promising developments in neuropsychological approaches for the detection of preclinical Alzheimer’s disease: a selective review.

Alzheimer's Research & Therapy 2013, 5:58 (21 November 2013)

Steven this is so very helpful, thank you!

Hi Amy,

An essential element that we look for in evaluating SCI is collateral informants who know the individual well and may be sensitive to early changes. Our group is very interested in PreMCI conditions, those conditions that do not meet strict criteria for mild cognitive impairment but are not cognitively normal. They are at increased risk for development of future MCI or dementia See Loewenstein, Duara et al., Alzheimer's Dement. 2012 May ; 8(3): 172–179. doi:10.1016/j.jalz.2011.03.002

Best, David

Pasted below is abstract from Nature: study of biomarker for predicting AD. Authors caution it is early days, need for replication, but it's something concrete.

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Plasma phospholipids identify antecedent memory impairment in older adults

Mark Mapstone,

Amrita K Cheema,

Massimo S Fiandaca,

Xiaogang Zhong,

Timothy R Mhyre,

Linda H MacArthur,

William J Hall,

Susan G Fisher,

Derick R Peterson,

James M Haley,

Michael D Nazar,

Steven A Rich,

Dan J Berlau,

Carrie B Peltz,

Ming T Tan,

Claudia H Kawas

& Howard J Federoff

Affiliations

Contributions

Corresponding author

Nature Medicine

(2014)

doi:10.1038/nm.3466

Received

27 August 2013

Accepted

09 January 2014

Published online

09 March 2014

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Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies2. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels3, structural and functional magnetic resonance imaging4 and the recent use of brain amyloid imaging5 or inflammaging6, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity7. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2–3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.

Lucy, thank you very much for this. I will request the full text for sure!

Hi Amy,

A colleague and I have developed the Subtle Cognitive Impairment Test (SCIT) that has proved very sensitive to minor deficits in cognitive function. You might want to look at Friedman, Yelland and Robinson (2011) Subtle cognitive impairment in elders with Mini-Mental State Examination scores within the 'normal' range. International Journal of Geriatric Psychiatry; 27(5):463-71

Hi Gregory,

Thank you for pointing this out to me, I have just located the paper and look forward to reading it. Very best wishes, Amy

Amy:

     Here's a link from Science: fabulous photograph of blood-brain barrier and also artist's rendering of b amyloid plaques being zapped by u/s: DOI: 10.1126/science.aab0302

Lucy I am sorry I didnt see your post here, thank you for sharing, it is fabulous!

Please let me know if the following references/sites are helpful to you:

1.  Subjective cognitive impairment: Towards early identification of ...

www.sciencedirect.com/science/article/pii/S2173580816300840

by S Garcia-Ptacek - ‎2016 - ‎Cited by 7 - ‎Related articles

Aug 30, 2016 - Neurodegeneration in Alzheimer disease (AD) begins decades before dementia and patients with mild cognitive impairment (MCI) already ...

2.  From mild cognitive impairment to subjective cognitive decline ...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317337/

by YW Cheng - ‎2017 - ‎Cited by 5 - ‎Related articles

Feb 16, 2017 - Identification of subjects at the early stages of Alzheimer's disease (AD) is fundamental for drug development and possible intervention or ...

Dennis

Dennis Mazur

Thank you for the suggestions Dennis! I had identified and used these references but thank you again for your help.

Amy