Atrophy Subtypes May Predict Cognitive Decline Patterns, Rates of Conversion to Dementia

Vincent Planche, MD, PhD

Results from a study evaluating outpatients with either subjective cognitive decline complaint (SCC) or mild cognitive impairment (MCI) demonstrated that different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia can be predicted by atrophy subtype categorization.

Researchers found that the rate of cognitive decline was accelerated in the typical/diffuse atrophy and the limbic predominant atrophy groups, especially on the Mini Mental State Examination (MMSE; typical/diffuse atrophy: ß = –0.70; 95% CI, –0.99 to –0.41; limbic-predominant atrophy: ß = –0.48; 95% CI, –0.77 to –0.18).

Led by Vincent Planche, MD, PhD, neurologist, Centre Mémoire Ressources Recherche, in Lyon , France, the data included 2083 outpatients from the MEMENTO cohort that were followed for 4 years without knowing prior amyloid status. In addition to a faster rate of cognitive decline, those with typical/diffuse atrophy were associated with the highest risk of developing dementia and Alzheimer disease (AD) over time.

This observation was made in both the whole analytic sample and in the amyloid-positive participants. The dementia incidence rate differed across atrophy subtypes (P <.0001) and was almost 5-fold higher for the typical/diffuse group (6.6 per 100 patient-years [PY]; 95% CI, 5.5–7.9;) compared to the minimal/no atrophy group (1.4 per 100 PY; 95% CI, 1.0–1.9).

"We decided to reverse this pathophysiological reasoning and deliberately did not restrict our analyses to patients with AD-positive biomarkers. By doing so, we were able to assess brain atrophy subtypes as a ‘primary’ classifier, which is more relevant from epidemiological and clinical standpoints,” Planche et al concluded.

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In total, 142 of the 213 (66.7%) incident cases of dementia were of the AD type. Etiologies of dementia were significantly different among groups, with an overrepresentation of Lewy body dementia in the hippocampal-sparing atrophy and in the minimal/no atrophy groups (8.7% and 14.6%, respectively) as compared to the typical/diffuse (4.2%) and limbic-predominant groups (4.5%).

There was an association between increased risk of dementia in typical/diffuse atrophy restricted to amyloid-positive participants (hazard ratio [HR], 3.24; 95% CI, 1.75–5.99; c = 0.72; 95% CI, 0.66-0.78), and amyloid-negative participants (HR, 4.49; 95% CI, 1.52–13.53). Notably, the interaction between atrophy subtypes and the amyloid status was non-significant (P = .51).

Among a group of 864 participants whose amyloid status was available, the group presented with similar median MMSE scores at baseline (median, 28; P = .17) to those with unknown amyloid status but had the same age at study entry (P = .35).

In addition to the MMSE, cognitive decline was accelerated in the typical/diffuse atrophy and the limbic predominant atrophy groups on other measures such as the Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB; typical/diffuse atrophy: ß = 0.27; 95% CI, 0.22–0.33; limbic predominant: ß = 0.07; 95% CI, –0.01 to 0.15), and Free and Cued Selective Reminding Test (FCSRT) free recall (ß = –0.73; 95% CI, –1.48 to 0.01; ß = –0.53; 95% CI, –1.29 to 0.23, respectively).

"Another strength of the current study in terms of extending the brain atrophy subtype concept is that our sample is completely independent of the ADNI cohorts, unlike most previous works in the field,” the study authors concluded.

They went on to write that the majority of previous longitudinal studies that investigated rates of decline in relation to brain atrophy subtypes were based on data sets extracted from Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts, raising the possibility of selection biases that could preclude generalization to worldwide clinical practice, much less to the general population.

REFERENCE

Planche V, Bouteloup V, Mangin J, et al. Clinical relevance of brain atrophy subtypes categorization in memory clinics. Alzheimers Dement. Published online December 15, 2020. doi: 10.1002/alz.12231