Anna-Karin Berger

Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis.

To determine the size of the impairment across different cognitive domains in preclinical Alzheimers disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (< 75 years) and shorter follow-up intervals (< 3 years) were associated with larger effect sizes for both global cognitive ability and episodic memory. For global cognitive ability, studies that used population-based sampling yielded larger effect sizes; for episodic memory, larger differences were seen in studies that preidentified groups in terms of baseline cognitive impairment. Within episodic memory, delayed testing and recall-based assessment resulted in the largest effect sizes. The authors conclude that deficits in multiple cognitive domains are characteristic of AD several years before clinical diagnosis. The generalized nature of the deficit is consistent with recent observations that multiple brain structures and functions are affected long before the AD diagnosis.

The occurrence of depressive symptoms in the preclinical phase of AD: A population-based study

Objective: To examine preclinical depressive symptoms 3 years before the diagnosis of AD. Methods: The authors compared incident AD patients and nondemented individuals in terms of baseline mood- and motivation-related symptoms of depression, and assessed whether depressive symptoms in preclinical AD are related to self-perceived memory problems. Participants came from a population-based longitudinal study on aging and dementia in Stockholm, Sweden. The sample consisted of 222 persons older than 74 years who were followed for a 3-year interval. Thirty-four individuals had developed AD at follow-up, whereas 188 remained nondemented. Dementia diagnosis was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. Depressive symptoms were assessed by the Comprehensive Psychopathological Rating Scale. Results: The incident AD patients had more depressive symptoms than the nondemented persons at baseline. There was a dominance of motivation-related symptoms of depression (e.g., lack of interest, loss of energy, concentration difficulties) in preclinical AD. This association remained when adjusting for subjective memory complaints. Conclusions: Depressive symptoms are elevated preclinically in AD, and this elevation is not merely a by-product of self-perceived cognitive difficulties. Thus, depressive symptoms may be part of the preclinical phase in AD.

Multiple cognitive deficits during the transition to Alzheimer's disease

The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at‐risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimers disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain‐based) in order to increase prediction accuracy.

Depression does not aggravate the episodic memory deficits associated with Alzheimer's disease.

In a population-based study of persons between 75 and 96 years of age, normal old adults (n = 296), patients with Alzheimers disease (AD; n = 45), and patients with concomitant AD and depression (AD-D; n = 9) were compared on free recall and recognition of slowly and rapidly presented words and digit span. With the exception of forward digit span, the normal old group outperformed the 2 AD groups across all tasks. In free recall, only the normal old group performed better as task pacing decreased; however, all groups benefited from more study time in recognition. This suggests that both AD and AD-D patients have deficits in the ability to use more study time for remembering. Of most importance, the 2 AD groups were indistinguishable for all task variables. This lack of comorbidity effects is discussed relative to the view that depression, much like many other individual-difference variables that affect memory performance in normal aging, may be overshadowed by the influence of the neurodegenerative process in AD.

Negligible effects of depression on verbal and spatial performance in Alzheimer's disease.

We examined whether a diagnosis of depression affects verbal and visuospatial performance in Alzheimer’s disease (AD). Using data from a population-based study, persons with AD and depression (AD/D), AD alone and a control group of normal older adults were compared in two tests of verbal ability (category and letter fluency) and two tests of visuospatial skill (block design and clock drawing). As expected, there were clear AD-related deficits across all cognitive tasks. More importantly, the AD and AD/D groups were indistinguishable on all task variables. The lack of effects of depression was discussed relative to the view that those symptoms of this disease which are especially detrimental to cognitive functioning (e.g. concentration difficulties, lack of interest, loss of energy) may already be present in AD as a result of the neurodegenerative process.

Alzheimer's Disease and Depression: Preclinical Comorbidity Effects on Cognitive Functioning

Both Alzheimers disease (AD) and depression (D) are prevalent disorders in old age and may co-occur in the same individual. The present study examined whether a diagnosis of D in AD has negative effects on cognitive functioning in the preclinical stage of the diseases, as well as at the time when the diagnoses were rendered. Population-based samples of 13 individuals with incident AD and D, 109 incident AD cases without D, and 179 normal older adults were followed over a three-year period. The groups were compared preclinically and at the time of diagnosis on global cognitive functioning using the MMSE total and the specific item scores, as well as the occurrence of depressive symptoms. As expected, there were clear AD-related deficits preclinically, which were exacerbated at follow-up. In addition, there were D-related deficits on three MMSE items (i.e., following commands, reading, and writing). The poorer performance on the three MMSE items was linked to an elevation of depressive symptoms. However, D was not associated with greater decline in cognitive functioning over the three-year follow-up period. Thus, although depressive symptoms may result in slight cognitive deficits in preclinical AD, at the time of the dementia diagnosis these effects may be absorbed by the neurodegenerative process.

Differential effects of depressive symptoms on prospective and retrospective memory in old age

The effects of depressive symptoms on prospective and retrospective memory were examined in a population-based sample of elderly persons (n = 404). Depression was assessed using the Comprehensive Psychopathological Rating Scale and treated as a continuous variable. The variation in depressive symptoms ranged from no symptoms to presence of a clinical depression. Depressive symptoms had a negative effect on consolidation and retrieval in retrospective memory. However, the retrospective, but not the prospective, component of prospective memory was affected by depression. The findings are discussed in light of medial-temporal lobe alterations in depression.

Negligible effects of depression on verbal and spatial performance in Alzheimer's disease

We examined whether a diagnosis of depression affects verbal and visuospatial performance in Alzheimers disease (AD). Using data from a population-based study, persons with AD and depression (AD/D), AD alone and a control group of normal older adults were compared in two tests of verbal ability (category and letter fluency) and two tests of visuospatial skill (block design and clock drawing). As expected, there were clear AD-related deficits across all cognitive tasks. More importantly, the AD and AD/D groups were indistinguishable on all task variables. The lack of effects of depression was discussed relative to the view that those symptoms of this disease which are especially detrimental to cognitive functioning (e.g. concentration difficulties, lack of interest, loss of energy) may already be present in AD as a result of the neurodegenerative process.