A nosognosia, or loss of insight into one’s cognitive and functional problems, is one of the most common neuropsychiatric problems among patients with Alzheimer’s disease. Using clinically validated diagnostic criteria, we have recently reported that about 30% of patients with mild dementia have anosognosia.
1 Apathy is among the most common behavioral changes in Alzheimer’s disease.
2 The frequency of apathy in Alzheimer’s disease has been reported to range between 19% and 76%, and this discrepancy may be mainly related to different diagnostic methods and the inclusion of patients with different severities of dementia.
3 Cross-sectional studies reported a significant association between anosognosia and apathy,
4 but to our knowledge, whether anosognosia may predict apathy or vice versa has never been examined. Furthermore, longitudinal studies of apathy and anosognosia in Alzheimer’s disease are few.
5,
6 In recent longitudinal studies we found that apathy in Alzheimer’s disease is a significant predictor of depression, faster functional and cognitive decline, and more severe parkinsonism.
5,
7DISCUSSION
To our knowledge, this is the first study to examine the association between apathy and anosognosia among patients with Alzheimer’s disease in the context of a longitudinal study. The main finding was that anosognosia at baseline was a significant predictor of more severe apathy at follow-up. Additional relevant findings were that the severity of both anosognosia and apathy significantly increased over time, suggesting that these phenomena are robust psychological and behavioral constructs in Alzheimer’s disease, and that remission is rare.
Before further comments, several limitations of our study should be pointed out. First, 24% of our baseline sample did not have a follow-up. However, there were no significant differences between patients with or without a follow-up on the main demographic variables. Second, the follow-up assessment ranged from 1 to 4 years after baseline, but there were no between-group differences on the mean duration of follow-up. Third, a small group of patients (11% of the sample) had anosognosia at baseline but no anosognosia at follow-up, and this interesting phenomenon of improved awareness in dementia will require further studies in larger samples. This finding could be related to patients being repeatedly confronted with their functional limitations in the context of preserved self-knowledge learning abilities. Finally, an important question is whether patients with anosognosia throughout follow-up had more severe apathy at follow-up than patients who developed anosognosia during the follow-up. We only had eight patients who developed anosognosia during the follow-up period and had no apathy at baseline, and future studies with larger samples should examine this interesting issue.
Anosognosia is a clinically relevant phenomenon in Alzheimer’s disease. In a recent study, we found that anosognosia is already present in about one-third of patients with mild dementia and is associated with memory and language deficits.
1 Apathy is among the most frequent relevant behavioral changes in Alzheimer’s disease, and we have recently demonstrated that it predicts more severe depression, a faster cognitive and functional decline, and more severe parkinsonism.
5,
7Cross-sectional studies reported a significant association between anosognosia and apathy in Alzheimer’s disease.
14 Our present study examined the direction of this association, and the main finding was that patients with anosognosia had a significantly greater increment on apathy scores over time relative to patients without anosognosia. The question now arises as to the mechanism of this association. One possibility is that patients with depression may have an increased rating for developing apathy, but we demonstrated recently that depression at baseline does not predict apathy at follow-up.
5Anosognosia and apathy are both related to frontal lobe dysfunction. Recent studies showed a significant association between apathy in Alzheimer’s disease and metabolic and pathological changes in specific regions of the frontal lobes. We found a significant association between apathy and the volume of frontal white matter hyperintensities in Alzheimer’s disease patients assessed with MRI volumetry.
19 Marshall et al.
20 found that apathy scores (as measured with the Neuropsychiatric Inventory) were significantly correlated with neurofibrillary tangle counts in the anterior cingulate. Using structural MRI, the same group reported a significant positive correlation between apathy severity and gray matter atrophy in the bilateral anterior cingulate and the left medial frontal cortex.
21 Using fluorodeoxyglucose positron emission tomography (FDG-PET), Marshall et al.
22 reported that Alzheimer’s disease patients with apathy had significantly more severe hypometabolism in the bilateral anterior cingulate region than subjects without apathy. Finally, an MRI volumetric study
23 confirmed the association between apathy and more severe bilateral gray matter atrophy in the anterior cingulate, orbitofrontal cortex, and frontal dorsolateral cortex. The involvement of the anterior cingulate in most of the above studies is of interest, since this structure has been consistently related to the initiation of motivated goal-orientated behaviors.
24Similarly, anosognosia in Alzheimer’s disease has also been related to frontal lobe dysfunction. In an early study using single photon emission CT that included 12 Alzheimer’s disease patients with anosognosia and 12 patients without anosognosia matched for age, duration of illness, and cognitive impairment, we found that patients with anosognosia had significant perfusion deficits in the right frontal lobe relative to the comparison group.
25 More recent FDG-PET studies showed significant correlations between increased anosognosia scores and lower metabolism in bilateral dorsolateral frontal temporo-parietal, left inferior frontal, and orbitofrontal regions.
26To summarize, there is strong evidence that both anosognosia and apathy are related to dysfunction in specific frontal regions. The present finding that anosognosia predicts more severe apathy suggests an asynchrony in frontal lobe involvement in Alzheimer’s disease: whereas anosognosia may arise as an early response to frontal lobe damage, apathy may develop with further frontal involvement.
An alternative explanation for the present findings is that patients with anosognosia may have a poorer adaptation response to their functional limitations than patients without anosognosia. More specifically, when Alzheimer’s disease patients with good awareness are faced with severe limitations performing some of their usual interests and chores due to the increasing cognitive impairment, they may look for and engage in activities that are compatible with their current functional capacities. On the other hand, patients with anosognosia may fail to search for alternative activities due to their inability to recognize their increasing functional limitations. Patients with anosognosia may become frustrated (which may account for the increased irritability often reported in this group
27 ) and may eventually lose motivation for most activities.
In conclusion, our study demonstrated that both anosognosia and apathy in Alzheimer’s disease increased significantly in severity after a mean period of 18 months. We also demonstrated that anosognosia is a significant predictor of apathy in Alzheimer’s disease. Future studies should examine whether this clinically relevant association is related to regional variances in the progression of Alzheimer’s disease neuropathology and/or to behavioral changes and adjustment difficulties produced by loss of awareness.