Summary: Alzheimer’s risk is increased for those with anosognosia, a condition in which sufferers are unaware they are experiencing memory loss.
While memory loss is an early symptom of Alzheimer’s disease, its presence doesn’t mean a person will develop dementia. A new study at the Centre for Addiction and Mental Health (CAMH) has found a clinically useful way to predict who won’t develop Alzheimer’s disease, based on patients’ awareness of their memory problems.
People who were unaware of their memory loss, a condition called anosognosia, were more likely to progress to Alzheimer’s disease, according to the study, published today in the Journal of Clinical Psychiatry. Those who were aware of memory problems were unlikely to develop dementia.
“If patients complain of memory problems, but their partner or caregiver isn’t overly concerned, it’s likely that the memory loss is due to other factors, possibly depression or anxiety,” says lead author Dr. Philip Gerretsen, Clinician Scientist in CAMH’s Geriatric Division and Campbell Family Mental Health Research Institute. “They can be reassured that they are unlikely to develop dementia, and the other causes of memory loss should be addressed.”
In other cases, the partner or caregiver is more likely to be distressed while patients don’t feel they have any memory problems. In Alzheimer’s disease, lack of awareness is linked to more burden on caregivers. Both unawareness of illness (anosognosia) and memory loss (known as mild cognitive impairment) can be objectively assessed using questionnaires.
The study, believed to be the largest of its kind on illness awareness, had data on 1,062 people aged 55 to 90 from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This included 191 people with Alzheimer’s disease, 499 with mild cognitive impairment and 372 as part of the healthy comparison group.
The researchers also wanted to identify which parts of the brain were affected in impaired illness awareness. They examined the brain’s uptake of glucose, a type of sugar. Brain cells need glucose to function, but glucose uptake is impaired in Alzheimer’s disease.
Using PET brain scans, they showed that those with impaired illness awareness also had reduced glucose uptake in specific brain regions, even when accounting for other factors linked to reduced glucose uptake, such as age and degree of memory loss.
As the next stage of this research, Dr. Gerretsen will be tracking older adults with mild cognitive impairment who are receiving an intervention to prevent Alzheimer’s dementia. This ongoing study, the PACt-MD study, combines brain training exercises and brain stimulation, using a mild electrical current to stimulate brain cells and improve learning and memory. While the main study is focused on dementia prevention, Dr. Gerretsen will be looking at whether the intervention improves illness awareness in conjunction with preventing progression to dementia.
Funding: Ontario Mental Health Foundation, Canadian Institutes of Health Research, National Institutes of Health, CAMH, Alzheimer’s Disease Neuroimaging Initiative funded this study.
Source: Stacy Brooks – CAMH
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Anosognosia Is an Independent Predictor of Conversion From Mild Cognitive Impairment to Alzheimer’s Disease and Is Associated With Reduced Brain Metabolism” by Philip Gerretsen, MD, PhD, FRCPC; Jun Ku Chung, BSc; Parita Shah, BSc; Eric Plitman, BSc; Yusuke Iwata, MD; Fernando Caravaggio, PhD; Shinichiro Nakajima, MD, PhD; Bruce G. Pollock, MD, PhD, FRCPC; and Ariel Graff-Guerrero, MD, PhD; for the Alzheimer’s Disease Neuroimaging Initiative in Journal of Clinical Psychiatry. Published online October 2017 doi:10.4088/JCP.16m11367
Anosognosia Is an Independent Predictor of Conversion From Mild Cognitive Impairment to Alzheimer’s Disease and Is Associated With Reduced Brain Metabolism
Objective: Anosognosia, or impaired illness awareness, is a common feature of Alzheimer’s disease (AD) and less so of mild cognitive impairment (MCI). Importantly, anosognosia negatively influences clinical outcomes for patients and their caregivers and may predict the conversion from MCI to AD. This study aimed to examine (1) the relationship between brain glucose metabolism as measured by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and anosognosia in patients with MCI and AD and (2) the predictive utility of anosognosia in patients with MCI for later conversion to AD, even when controlling for other factors, including gender, education, apolipoprotein E ε4 carrier status, dementia severity, and cognitive dysfunction.
Methods: Data for 1,062 participants from the Alzheimer’s Disease Neuroimaging Initiative database (2003 to August 2015) classified as having AD (n = 191) or MCI (n = 499) or as healthy comparison (HC) subjects (n = 372) were analyzed. HC participants had Mini-Mental State Examination (MMSE) scores from 24 to 30 and a Clinical Dementia Rating (CDR) of 0. MCI participants had MMSE scores from 24 to 30, a memory complaint, objective memory loss, a CDR of 0.5, absence of significant levels of impairment in other cognitive domains, and essentially preserved activities of daily living. AD participants had MMSE scores ≤ 26 and a CDR of ≥ 0.5, and met National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria for probable AD. Anosognosia was measured with the composite discrepancy score of the study partner and participants’ scores on the Everyday Cognition scale (ECog). Bivariate correlations and multiple regression analyses were performed to assess the relationship between anosognosia and FDG-PET findings in each group. Lastly, logistic regression and receiver operating characteristic curve analyses were performed in the MCI sample to determine if anosognosia was predictive of conversion from MCI to AD.
Results: Hypometabolism was independently associated with anosognosia in AD, particularly in the posterior cingulate cortex and right angular gyrus. Anosognosia was associated with conversion from MCI to AD within 5 years (OR = 2.74 [95% CI, 1.95 to 3.85], χ21 = 33.65, P < .001), even after including covariates (OR = 1.64 [95% CI, 1.12 to 2.40], χ21 = 6.43, P = .011). ECog-composite scores ≤ −0.75 were 93% sensitive and 15% specific for conversion from MCI to AD.
Conclusions: Anosognosia in AD is related to brain glucose hypometabolism. Further, anosognosia independently predicts conversion from MCI to AD. The absence of anosognosia may be clinically useful to identify those patients that are unlikely to convert from MCI to AD.
“Anosognosia Is an Independent Predictor of Conversion From Mild Cognitive Impairment to Alzheimer’s Disease and Is Associated With Reduced Brain Metabolism” by Philip Gerretsen, MD, PhD, FRCPC; Jun Ku Chung, BSc; Parita Shah, BSc; Eric Plitman, BSc; Yusuke Iwata, MD; Fernando Caravaggio, PhD; Shinichiro Nakajima, MD, PhD; Bruce G. Pollock, MD, PhD, FRCPC; and Ariel Graff-Guerrero, MD, PhD; for the Alzheimer’s Disease Neuroimaging Initiative in Journal of Clinical Psychiatry. Published online October 2017 doi:10.4088/JCP.16m11367