Is Alzheimer's Disease Really What We Think It Is?

Written By: W. Howard Buddin Jr., Ph.D.
Published On: 08/27/2013

An estimated 5.4 million Americans have Dementia of the Alzheimer’s Type (AD). This includes approximately 200,000 individuals with early onset AD (under the age of 65; Alzheimer’s Association, 2012). Alzheimer’s is a neuropathological disease that is well in motion by the time memory or other cognitive problems surface and a patient is referred to a memory clinic. Some evidence suggests Alzheimer’s pathology begins in different areas of the brain stem, but symptoms (like memory dysfunction) appear later in the course of the disease when cortical regions become dysfunctional. One main goal of current research is to detect the presence of the disease, prior to symptom onset, so appropriate interventions can be developed.

To accomplish research goals that seek to identify pre-symptomatic phases of Alzheimer’s, the clinical criteria for AD are being honed. McKhann, et al. (2011) propose a sweeping restructuring of the original criteria (codified in 1984) that incorporates more modern and well-accepted research that shifted our understanding of AD as a disease and syndrome. They have proposed three classification criteria for AD dementia, the last of which is intended for research purposes:

  1. Probable AD dementia,
  2. Possible AD dementia, and
  3. Probable or possible AD dementia with evidence of the AD pathophysiological process.

Also included are criteria for “Pathophysiologically proved AD dementia,” which would be appropriate if

…the patient meets the clinical and cognitive criteria for AD dementia…and the neuropathological examination…demonstrates the presence of the AD pathology.

Memory Impairment as a Defining Characteristic?

Although memory impairment is and has been the primary defining feature of AD, it is unlikely that it will continue to be a necessary (it has never been sufficient) condition when diagnosing AD (Mckhann, 2011). Among proposed subtypes are non-amnestic types marked prominently by deficits in either language (e.g., word-finding difficulties), spatial cognition (e.g., object agnosia, impaired face, recognition, simultanagnosia, and alexia) or executive dysfunction (e.g., impaired reasoning, judgment, and problem solving).

Genetic Biomarkers and Neurocognitive Change

Advances since the 1984 Alzheimer’s criteria include the discovery of potential AD biomarkers. Specifically, genetic mutations in APP, PSEN1, and PSEN2 and biomarkers including amyloid-beta protein and tau/p-tau are measured, when possible, to assist with diagnosis. The presence of these biomarkers has demonstrated good reliability and validity in establishing a positive diagnosis of AD.

Neuropsychological testing has also advanced in its ability to detect early clinical signs of Alzheimer’s. As noted by Bondi, Jak, Delano-Wood, Jacobson, Delis, and Salmon (2008) in their review of literature covering neuropsychological testing for AD:

“The neuropsychological studies indicated that prodromal AD is characterized by subtle deficits in a broad range of neuropsychological domains, particularly in learning and memory, executive functioning, processing speed, attention, and semantic knowledge.”

In particular, and poignantly:

“Thus, there exist several potential markers of a prodromal period of AD, in which specific cognitive and biomarker changes precede the clinical manifestations.”

In the Trenches

The neuropathological criteria used to diagnose various neurodegenerative disorders are evolving. The clinical criteria are also evolving and, as a result, we know a number of different cognitive syndromes can be associated with the same disease. Posterior cortical atrophy, logopenic aphasia, or a primary amnestic syndrome, for instance, can all be linked to “Alzheimer’s Disease.” Of course, as neuropsychologists, we want to be able to provide a diagnosis to the patient and their family; however, providing a diagnosis and describing a syndrome serve entirely different functions. Eventually, genetic markers and morphological and metabolic brain imaging will be able to identify the disease and, hopefully lead to effective interventions well before symptoms emerge. Now, in 2013, the neuropsychological test data provide the bulk of the information about the patient’s current level of cognitive functioning, their strengths and weaknesses, the types of everyday difficulties they are most likely to experience, and how their overall quality of life can be maintained as long as possible in the face of a dementing illness. As medical technology advances, it is important to remember that our job is not only to diagnose, but to measure and describe cognitive functions in a manner that can ultimately improve the daily existence of patients and caregivers.

References

Alves, Jorge, Soares, José Miguel, Sampaio, Adriana, Gonçalves, Óscar F (2013). Posterior cortical atrophy and Alzheimer’s disease: a meta-analytic review of neuropsychological and brain morphometry studies. Brain Imaging and Behavior, 1–9. doi: 10.1007/s11682–013–9236–1

Association, Alzheimer’s (2012). 2012 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 8(2), 131–168. doi:10.1016/j.jalz.2012.02.001. http://dx.doi.org/10.1016/j.jalz.2012.02.001

Bondi, Mark W., Jak, Amy J., Delano-Wood, Lisa, Jacobson, Mark W., Delis, Dean C., & Salmon, David P. (2008). Neuropsychological contributions to the early identification of Alzheimer’s Disease. Neuropsychology Review, 18(1), 73–90. doi: 10.1007/s11065–008–9054–1

Mckhann, Guy M, Knopman, David S, Chertkow, Howard, Hyman, Bradley T, Jack, Clifford R, Kawas, Claudia H, et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3), 263–269. doi:10.1016/j.jalz.2011.03.005

Savla, Gauri Nayak, Palmer, Barton W. (2005). Neuropsychology in Alzheimer’s disease and other dementia research. Current Opinion in Psychiatry, 18, 621–627.

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